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Sample records for hereditary sensory ataxic

  1. [Pathophysiology of sensory ataxic neuropathy].

    Science.gov (United States)

    Sobue, G

    1996-12-01

    The main lesions of sensory ataxic neuropathy such as chronic idiopathic sensory ataxic neuropathy, (ISAN), carcinomatous neuropathy, Sjögren syndrome-associated neuropathy and acute autonomic and sensory neuropathy (AASN) are the large-diameter sensory neurons and dosal column of the spinal cord and the large myelinated fibers in the peripheral nerve trunks. In addition, afferent fibers to the Clarke's nuclei are also severely involved, suggesting Ia fibers being involved in these neuropathies. In NT-3 knockout mouse, an animal model of sensory ataxia, large-sized la neurons as well as muscle spindle and Golgi tendon organs are depleted, and are causative for sensory ataxia. Thus, the proprioceptive Ia neurons would play a role in pathogenesis of sensory ataxia in human sensory ataxic neuropathies, but the significance of dorsal column involvement in human sensory ataxia is still needed to evaluate.

  2. Pyridoxine-induced sensory ataxic neuronopathy and neuropathy: revisited.

    Science.gov (United States)

    Kulkantrakorn, Kongkiat

    2014-11-01

    High dose pyridoxine is neurotoxic. Previous case reports were sparse and little is known about the clinical and electrodiagnostic findings. Three patients with pyridoxine-induced sensory ataxic neuropathy were studied and a review of the involved literature was performed. Three patients, aged 80, 83 and 83 years old, presented with sensory ataxia for 3-8 months. Examination showed signs of polyneuropathy and sensory ataxia. Six hundred milligrams of pyridoxine was consumed each day for 3-10 years, in the form of vitamin B1-6-12 combination tablet. Investigations for other causes of neuropathy were unremarkable. Blood levels of vitamin B6 were markedly elevated at 104.6, 81.4 and 66.9 times of upper normal limits. Electrodiagnostic tests showed symmetric axonal sensory polyneuropathy in two patients. Two years after vitamin discontinuation, all patients showed no significant improvement in the neuropathy and gait. In conclusion, consumption of high dose pyridoxine can cause sensory neuronopathy and axonal sensorimotor polyneuropathy, leading to sensory ataxia which may not be reversible.

  3. Hereditary sensory and autonomic neuropathies.

    Science.gov (United States)

    Auer-Grumbach, Michaela

    2013-01-01

    Hereditary sensory and autonomic neuropathies (HSN/HSAN) are clinically and genetically heterogeneous disorders of the peripheral nervous system that predominantly affect the sensory and autonomic neurons. Hallmark features comprise not only prominent sensory signs and symptoms and ulcerative mutilations but also variable autonomic and motor disturbances. Autosomal dominant and autosomal recessive inheritance has been reported. Molecular genetics studies have identified disease-causing mutations in 11 genes. Some of the affected proteins have nerve-specific roles but underlying mechanisms have also been shown to involve sphingolipid metabolism, vesicular transport, structural integrity, and transcription regulation. Genetic and functional studies have substantially improved the understanding of the pathogenesis of the HSN/HSAN and will help to find preventive and causative therapies in the future.

  4. Hereditary sensory neuropathy type I

    Directory of Open Access Journals (Sweden)

    Auer-Grumbach Michaela

    2008-03-01

    Full Text Available Abstract Hereditary sensory neuropathy type I (HSN I is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7 identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN, especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra

  5. Sensory ataxic neuropathy with dysarthria/dysphagia and ophthalmoplegia (SANDO). Two case reports.

    Science.gov (United States)

    Gáti, István; Danielsson, Olof; Jonasson, Jon; Landtblom, Anne-Marie

    2011-12-01

    Case histories of two unrelated patients suffering from sensory ataxic neuropathy, dysarthria/dysphagia and external ophthalmoplegia (SANDO) are reported. Both patients showed compound heterozygosity for POLG1 gene mutations, and presented with symptom of the clinical characteristics of SANDO. A patient with a p.A467T and p.W748S, well-known mutations showed a progressive course with early onset and multisystem involvement, including symptoms characteristics for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). The second patient showed a less well-known p.T251I and p.G848S mutations with late onset and dysphagia/dysarthria dominated, moderate symptoms. This later is the second published case history, when these POLG1 gene mutations are the possible background of late onset SANDO, dominantly presenting with bulbar symptoms.

  6. Genetics Home Reference: hereditary sensory and autonomic neuropathy type V

    Science.gov (United States)

    ... Conditions HSAN5 hereditary sensory and autonomic neuropathy type V Enable Javascript to view the expand/collapse boxes. ... All Description Hereditary sensory and autonomic neuropathy type V ( HSAN5 ) is a condition that primarily affects the ...

  7. Molecular genetics of hereditary sensory neuropathies.

    Science.gov (United States)

    Auer-Grumbach, Michaela; Mauko, Barbara; Auer-Grumbach, Piet; Pieber, Thomas R

    2006-01-01

    Hereditary sensory neuropathies (HSN), also known as hereditary sensory and autonomic neuropathies (HSAN), are a clinically and genetically heterogeneous group of disorders. They are caused by neuronal atrophy and degeneration, predominantly affecting peripheral sensory and autonomic neurons. Both congenital and juvenile to adulthood onset is possible. Currently, the classification of the HSN depends on the mode of inheritance, age at onset, and clinical presentation. Hallmark features are progressive sensory loss, chronic skin ulcers, and other skin abnormalities. Spontaneous fractures and neuropathic arthropathy are frequent complications and often necessitate amputations. Autonomic features vary between different subgroups. Distal muscle weakness and wasting may be present and is sometimes so prominent that it becomes difficult to distinguish HSN from Charcot-Marie-Tooth syndrome. Recent major advances in molecular genetics have led to the identification of seven gene loci and six-disease causing genes for autosomal-dominant and autosomal-recessive HSN. These genes have been shown to play roles in lipid metabolism and the regulation of intracellular vesicular transport, but also a presumptive transcriptional regulator, a nerve growth factor receptor, and a nerve growth factor have been described among the causative genes in HSN. Nevertheless, it remains unclear how mutations in the known genes lead to the phenotype of HSN. In this review, we summarize the recent progress of the molecular genetics of the HSN and the implicated genes.

  8. [A case of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis with multiple mitochondrial DNA deletions].

    Science.gov (United States)

    Tanaka, Koji; Tateishi, Takahisa; Kawamura, Nobutoshi; Ohyagi, Yasumasa; Urata, Michiyo; Kira, Jun-ichi

    2013-01-01

    We report the case of a 62-year-old man with sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO). He developed gait disturbance at 54 years of age, muscle weakness at 56 years, and difficulty hearing at 58 years. His brother had muscle weakness in both legs from age 20 years, and was diagnosed with Charcot-Marie-Tooth disease because he had muscle weakness of the four extremities, decreased CMAP and SNAP amplitudes on peripheral nerve conduction tests, and loss of large myelinated fibers and onion-bulb formations on sural nerve biopsy. His brother died aged 46 years, but no accurate cause of death was identified. Neurological examination of the present patient revealed bilateral ptosis, external ophthalmoparesis, dysarthria, dysphagia, sensorineural hearing loss, mild weakness and atrophy of proximal muscles in all four limbs, severe sensory ataxia, and disturbance of deep sensation in his legs. He showed elevation of lactate and pyruvate levels in cerebrospinal fluid and serum. An aerobic exercise test disclosed a marked increase in lactate and pyruvate levels in serum. On nerve conduction study, amplitudes of CMAP and SNAP, and F wave-evoked frequency were decreased. Needle electromyography showed chronic neurogenic patterns with fibrillation potentials in the extremity muscles. Head MRI demonstrated T2 prolonged lesions in the bilateral basal ganglia, while brain MRS revealed a small lactate peak. Biopsy of his left lateral vastus muscle showed ragged-red fibers and group atrophy, and some muscle fibers had decreased cytochrome c activity. Left sural nerve biopsy revealed a marked loss of large myelinated fibers, and some onion-bulb formations. Genetic testing disclosed a large mtDNA deletion in the biopsied muscle. Among nuclear genes, we found point mutations in ANT-1 (exon 1 c.105G>A, 5' untranslated region) and POLG-1 (exon 4, c.1218G>A, p. and exon 23 c.3920C>T, p.A1217V). We diagnosed SANDO. This is the first case of SANDO with large

  9. Can loss of muscle spindle afferents explain the ataxic gait in Riley–Day syndrome?

    OpenAIRE

    Macefield, Vaughan G.; Norcliffe-Kaufmann, Lucy; Gutiérrez, Joel; Axelrod, Felicia B.; Kaufmann, Horacio

    2011-01-01

    The Riley–Day syndrome is the most common of the hereditary sensory and autonomic neuropathies (Type III). Among the well-recognized clinical features are reduced pain and temperature sensation, absent deep tendon reflexes and a progressively ataxic gait. To explain the latter we tested the hypothesis that muscle spindles, or their afferents, are absent in hereditary sensory and autonomic neuropathy III by attempting to record from muscle spindle afferents from a nerve supplying the leg in 10...

  10. Hereditary sensory autonomic neuropathy and anaesthesia - a case report

    Directory of Open Access Journals (Sweden)

    Nandini Dave

    2007-01-01

    Full Text Available The hereditary sensory and autonomic neuropathies are a rare group of disorders characterized by progressive loss of function that predominantly affects the peripheral sensory nerves. Autonomic dysfunction is present to a variable degree and can have several implications for anaesthesia. We report the case of a patient with Hereditary sensory and autonomic neuropathy who was posted for a below knee amputation and discuss the anaesthesia management.

  11. Hereditary motor-sensory, motor, and sensory neuropathies in childhood.

    Science.gov (United States)

    Landrieu, Pierre; Baets, Jonathan; De Jonghe, Peter

    2013-01-01

    Hereditary neuropathies (HN) are categorized according to clinical presentation, pathogenic mechanism based on electrophysiology, genetic transmission, age of occurrence, and, in selected cases, pathological findings. The combination of these parameters frequently orients towards specific genetic disorders. Ruling out a neuropathy secondary to a generalized metabolic disorder remains the first pediatric concern. Primary, motor-sensory are the most frequent HN and are dominated by demyelinating AD forms (CMT1). Others are demyelinating AR forms, axonal AD/AR forms, and forms with "intermediate" electrophysiological phenotype. Pure motor HN represent40 genes with various biological functions have been found responsible for HN. Many are responsible for various phenotypes, including some without the polyneuropathic trait: for the pediatric neurologist, phenotype/genotype correlations constitute a permanent bidirectional exercise.

  12. Sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) in a sibling pair with a homozygous p.A467T POLG mutation.

    LENUS (Irish Health Repository)

    McHugh, John C

    2012-02-01

    Two siblings who developed fifth-decade-onset, concurrent progressive sensory ataxia, dysarthria, and ophthalmoparesis were found to be homozygous for the p.A467T mutation of the polymerase gamma (POLG) gene. The clinical course in both subjects was progression to severe disability. The enlarging spectrum of sensory ataxic neuropathies associated with mitochondrial DNA (mtDNA) instability and POLG mutations should be recognized and considered in the differential diagnosis of this unusual presentation.

  13. [Clinical practice of hereditary motor neuropathy (HMN) and hereditary sensory and autonomic neuropathy (HSAN)].

    Science.gov (United States)

    Takashima, Hiroshi

    2014-01-01

    Inherited neuropathy is a genetically and clinically heterogeneous group of neuropathies, the main category becomes Charcot-Marie-Tooth neuropathy (CMT), also known as hereditary motor and sensory neuropathy (HMSN), distal hereditary motor neuropathy (dHMN), and hereditary sensory autonomic neuropathy (HSAN). At least 80 genes have been associated with CMT, HMN or HSAN, a precise molecular diagnosis is often needed to make a clinical diagnosis accurately, enable genetic counseling of the patient and understanding of their molecular mechanisms. To identify the mutation in each patient, using a high-throughput NGS, we established a diagnostic procedure involving screening of disease causing genes in CMT, HMN or HSAN.

  14. Sensory ataxic neuropathy in golden retriever dogs is caused by a deletion in the mitochondrial tRNATyr gene.

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    Izabella Baranowska

    2009-05-01

    Full Text Available Sensory ataxic neuropathy (SAN is a recently identified neurological disorder in golden retrievers. Pedigree analysis revealed that all affected dogs belong to one maternal lineage, and a statistical analysis showed that the disorder has a mitochondrial origin. A one base pair deletion in the mitochondrial tRNA(Tyr gene was identified at position 5304 in affected dogs after re-sequencing the complete mitochondrial genome of seven individuals. The deletion was not found among dogs representing 18 different breeds or in six wolves, ruling out this as a common polymorphism. The mutation could be traced back to a common ancestor of all affected dogs that lived in the 1970s. We used a quantitative oligonucleotide ligation assay to establish the degree of heteroplasmy in blood and tissue samples from affected dogs and controls. Affected dogs and their first to fourth degree relatives had 0-11% wild-type (wt sequence, while more distant relatives ranged between 5% and 60% wt sequence and all unrelated golden retrievers had 100% wt sequence. Northern blot analysis showed that tRNA(Tyr had a 10-fold lower steady-state level in affected dogs compared with controls. Four out of five affected dogs showed decreases in mitochondrial ATP production rates and respiratory chain enzyme activities together with morphological alterations in muscle tissue, resembling the changes reported in human mitochondrial pathology. Altogether, these results provide conclusive evidence that the deletion in the mitochondrial tRNA(Tyr gene is the causative mutation for SAN.

  15. Disease mechanisms in hereditary sensory and autonomic neuropathies.

    Science.gov (United States)

    Verpoorten, Nathalie; De Jonghe, Peter; Timmerman, Vincent

    2006-02-01

    Inherited peripheral neuropathies are common monogenically inherited diseases of the peripheral nervous system. In the most common variant, i.e., the hereditary motor and sensory neuropathies, both motor and sensory nerves are affected. In contrast, sensory abnormalities predominate or are exclusively present in hereditary sensory and autonomic neuropathies (HSAN). HSAN are clinically and genetically heterogeneous and are subdivided according to mode of inheritance, age of onset and clinical evolution. In recent years, 6 disease-causing genes have been identified for autosomal dominant and recessive HSAN. However, vesicular transport and axonal trafficking seem important common pathways leading to degeneration of sensory and autonomic neurons. This review discusses the HSAN-related genes and their biological role in the disease mechanisms leading to HSAN.

  16. Hereditary sensory and autonomic neuropathies: types II, III, and IV

    OpenAIRE

    Axelrod Felicia B; Gold-von Simson Gabrielle

    2007-01-01

    Abstract The hereditary sensory and autonomic neuropathies (HSAN) encompass a number of inherited disorders that are associated with sensory dysfunction (depressed reflexes, altered pain and temperature perception) and varying degrees of autonomic dysfunction (gastroesophageal reflux, postural hypotention, excessive sweating). Subsequent to the numerical classification of four distinct forms of HSAN that was proposed by Dyck and Ohta, additional entities continue to be described, so that iden...

  17. [Hereditary sensory and motor neuropathy and hereditary sensory and autonomic neuropathies: recent advances].

    Science.gov (United States)

    Stojkovic, T

    2011-12-01

    This review summarizes the recent genetic advances in hereditary sensorimotor neuropathy also called Charcot-Marie-Tooth disease. The different new genes discovered in 2010 and their underlying phenotypes will be presented.

  18. Can loss of muscle spindle afferents explain the ataxic gait in Riley-Day syndrome?

    Science.gov (United States)

    Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Gutiérrez, Joel; Axelrod, Felicia B; Kaufmann, Horacio

    2011-11-01

    The Riley-Day syndrome is the most common of the hereditary sensory and autonomic neuropathies (Type III). Among the well-recognized clinical features are reduced pain and temperature sensation, absent deep tendon reflexes and a progressively ataxic gait. To explain the latter we tested the hypothesis that muscle spindles, or their afferents, are absent in hereditary sensory and autonomic neuropathy III by attempting to record from muscle spindle afferents from a nerve supplying the leg in 10 patients. For comparison we also recorded muscle spindles from 15 healthy subjects and from two patients with hereditary sensory and autonomic neuropathy IV, who have profound sensory disturbances but no ataxia. Tungsten microelectrodes were inserted percutaneously into fascicles of the common peroneal nerve at the fibular head. Intraneural stimulation within muscle fascicles evoked twitches at normal stimulus currents (10-30 µA), and deep pain (which often referred) at high intensities (1 mA). Microneurographic recordings from muscle fascicles revealed a complete absence of spontaneously active muscle spindles in patients with hereditary sensory and autonomic neuropathy III; moreover, responses to passive muscle stretch could not be observed. Conversely, muscle spindles appeared normal in patients with hereditary sensory and autonomic neuropathy IV, with mean firing rates of spontaneously active endings being similar to those recorded from healthy controls. Intraneural stimulation within cutaneous fascicles evoked paraesthesiae in the fascicular innervation territory at normal stimulus intensities, but cutaneous pain was never reported during high-intensity stimulation in any of the patients. Microneurographic recordings from cutaneous fascicles revealed the presence of normal large-diameter cutaneous mechanoreceptors in hereditary sensory and autonomic neuropathy III. Our results suggest that the complete absence of functional muscle spindles in these patients explains

  19. A case of hereditary sensory autonomic neuropathy type IV

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    G P Prashanth

    2012-01-01

    Full Text Available Hereditary sensory autonomic neuropathy type IV (HSAN -IV, also known as congenital insensitivity to pain with anhidrosis, is a very rare condition that presents in infancy with anhidrosis, absence of pain sensation and self -mutilation. Developmental delay and mental retardation are usually present. Ultrastructural study of the peripheral nerves demonstrates loss of the unmyelinated and small myelinated fibers. We here report a 8 year -old boy with HSAN IV with typical clinical features where the diagnosis was supported by nerve biopsy findings. However, our case was unusual since mental development was normal.

  20. Genes for hereditary sensory and autonomic neuropathies : a genotype-phenotype correlation

    NARCIS (Netherlands)

    Rotthier, Annelies; Baets, Jonathan; De Vriendt, Els; Jacobs, An; Auer-Grumbach, Michaela; Levy, Nicolas; Bonello-Palot, Nathalie; Kilic, Sara Sebnem; Weis, Joachim; Nascimento, Andres; Swinkels, Marielle; Kruyt, Moyo C.; Jordanova, Albena; De Jonghe, Peter; Timmerman, Vincent

    2009-01-01

    Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders characterized by axonal atrophy and degeneration, exclusively or predominantly affecting the sensory and autonomic neurons. So far, disease-associated mutations have been identified in seven g

  1. Disturbances in affective touch in hereditary sensory & autonomic neuropathy type III.

    Science.gov (United States)

    Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Löken, Line; Axelrod, Felicia B; Kaufmann, Horacio

    2014-07-01

    Hereditary sensory and autonomic neuropathy type III (HSAN III, Riley-Day syndrome, Familial Dysautomia) is characterised by elevated thermal thresholds and an indifference to pain. Using microelectrode recordings we recently showed that these patients possess no functional stretch-sensitive mechanoreceptors in their muscles (muscle spindles), a feature that may explain their lack of stretch reflexes and ataxic gait, yet patients have apparently normal low-threshold cutaneous mechanoreceptors. The density of C-fibres in the skin is markedly reduced in patients with HSAN III, but it is not known whether the C-tactile afferents, a distinct type of low-threshold C fibre present in hairy skin that is sensitive to gentle stroking and has been implicated in the coding of pleasant touch are specifically affected in HSAN III patients. We addressed the relationship between C-tactile afferent function and pleasant touch perception in 15 patients with HSAN III and 15 age-matched control subjects. A soft make-up brush was used to apply stroking stimuli to the forearm and lateral aspect of the leg at five velocities: 0.3, 1, 3, 10 and 30 cm/s. As demonstrated previously, the control subjects rated the slowest and highest velocities as less pleasant than those applied at 1-10 cm/s, which fits with the optimal velocities for exciting C-tactile afferents. Conversely, for the patients, ratings of pleasantness did not fit the profile for C-tactile afferents. Patients either rated the higher velocities as more pleasant than the slow velocities, with the slowest velocities being rated unpleasant, or rated all velocities equally pleasant. We interpret this to reflect absent or reduced C-tactile afferent density in the skin of patients with HSAN III, who are likely using tactile cues (i.e. myelinated afferents) to rate pleasantness of stroking or are attributing pleasantness to this type of stimulus irrespective of velocity.

  2. Mechanisms of disease in hereditary sensory and autonomic neuropathies.

    Science.gov (United States)

    Rotthier, Annelies; Baets, Jonathan; Timmerman, Vincent; Janssens, Katrien

    2012-01-24

    Hereditary sensory and autonomic neuropathies (HSANs) are a clinically and genetically heterogeneous group of disorders of the PNS. Progressive degeneration, predominantly of sensory and autonomic neurons, is the main pathological feature in patients with HSAN, and causes prominent sensory loss and ulcerative mutilations in combination with variable autonomic and motor disturbances. Advances in molecular genetics have enabled identification of disease-causing mutations in 12 genes, and studies on the functional effects of these mutations are underway. Although some of the affected proteins--such as nerve growth factor and its receptor--have obvious nerve-specific roles, others are ubiquitously expressed proteins that are involved in sphingolipid metabolism, vesicular transport, transcription regulation and structural integrity. An important challenge in the future will be to understand the common molecular pathways that result in HSANs. Unraveling the mechanisms that underlie sensory and autonomic neurodegeneration could assist in identifying targets for future therapeutic strategies in patients with HSAN. This Review highlights key advances in the understanding of HSANs, including insights into the molecular mechanisms of disease, derived from genetic studies of patients with these disorders.

  3. Hereditary sensory and autonomic neuropathies: types II, III, and IV.

    Science.gov (United States)

    Axelrod, Felicia B; Gold-von Simson, Gabrielle

    2007-10-03

    The hereditary sensory and autonomic neuropathies (HSAN) encompass a number of inherited disorders that are associated with sensory dysfunction (depressed reflexes, altered pain and temperature perception) and varying degrees of autonomic dysfunction (gastroesophageal reflux, postural hypotention, excessive sweating). Subsequent to the numerical classification of four distinct forms of HSAN that was proposed by Dyck and Ohta, additional entities continue to be described, so that identification and classification are ongoing. As a group, the HSAN are rare diseases that affect both sexes. HSAN III is almost exclusive to individuals of Eastern European Jewish extraction, with incidence of 1 per 3600 live births. Several hundred cases with HSAN IV have been reported. The worldwide prevalence of HSAN type II is very low. This review focuses on the description of three of the disorders, HSAN II through IV, that are characterized by autosomal recessive inheritance and onset at birth. These three forms of HSAN have been the most intensively studied, especially familial dysautonomia (Riley-Day syndrome or HSAN III), which is often used as a prototype for comparison to the other HSAN. Each HSAN disorder is likely caused by different genetic errors that affect specific aspects of small fiber neurodevelopment, which result in variable phenotypic expression. As genetic tests are routinely used for diagnostic confirmation of HSAN III only, other means of differentiating between the disorders is necessary. Diagnosis is based on the clinical features, the degree of both sensory and autonomic dysfunction, and biochemical evaluations, with pathologic examinations serving to further confirm differences. Treatments for all these disorders are supportive.

  4. Hereditary sensory and autonomic neuropathies: types II, III, and IV

    Directory of Open Access Journals (Sweden)

    Axelrod Felicia B

    2007-10-01

    Full Text Available Abstract The hereditary sensory and autonomic neuropathies (HSAN encompass a number of inherited disorders that are associated with sensory dysfunction (depressed reflexes, altered pain and temperature perception and varying degrees of autonomic dysfunction (gastroesophageal reflux, postural hypotention, excessive sweating. Subsequent to the numerical classification of four distinct forms of HSAN that was proposed by Dyck and Ohta, additional entities continue to be described, so that identification and classification are ongoing. As a group, the HSAN are rare diseases that affect both sexes. HSAN III is almost exclusive to individuals of Eastern European Jewish extraction, with incidence of 1 per 3600 live births. Several hundred cases with HSAN IV have been reported. The worldwide prevalence of HSAN type II is very low. This review focuses on the description of three of the disorders, HSAN II through IV, that are characterized by autosomal recessive inheritance and onset at birth. These three forms of HSAN have been the most intensively studied, especially familial dysautonomia (Riley-Day syndrome or HSAN III, which is often used as a prototype for comparison to the other HSAN. Each HSAN disorder is likely caused by different genetic errors that affect specific aspects of small fiber neurodevelopment, which result in variable phenotypic expression. As genetic tests are routinely used for diagnostic confirmation of HSAN III only, other means of differentiating between the disorders is necessary. Diagnosis is based on the clinical features, the degree of both sensory and autonomic dysfunction, and biochemical evaluations, with pathologic examinations serving to further confirm differences. Treatments for all these disorders are supportive.

  5. Genes for Hereditary Sensory and Autonomic Neuropathies: A Genotype-Phenotype Correlation

    Science.gov (United States)

    Rotthier, Annelies; Baets, Jonathan; De Vriendt, Els; Jacobs, An; Auer-Grumbach, Michaela; Levy, Nicolas; Bonello-Palot, Nathalie; Kilic, Sara Sebnem; Weis, Joachim; Nascimento, Andres; Swinkels, Marielle; Kruyt, Moyo C.; Jordanova, Albena; De Jonghe, Peter; Timmerman, Vincent

    2009-01-01

    Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders characterized by axonal atrophy and degeneration, exclusively or predominantly affecting the sensory and autonomic neurons. So far, disease-associated mutations have been identified in seven genes: two genes for autosomal dominant ("SPTLC1"…

  6. Genes for Hereditary Sensory and Autonomic Neuropathies: A Genotype-Phenotype Correlation

    Science.gov (United States)

    Rotthier, Annelies; Baets, Jonathan; De Vriendt, Els; Jacobs, An; Auer-Grumbach, Michaela; Levy, Nicolas; Bonello-Palot, Nathalie; Kilic, Sara Sebnem; Weis, Joachim; Nascimento, Andres; Swinkels, Marielle; Kruyt, Moyo C.; Jordanova, Albena; De Jonghe, Peter; Timmerman, Vincent

    2009-01-01

    Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders characterized by axonal atrophy and degeneration, exclusively or predominantly affecting the sensory and autonomic neurons. So far, disease-associated mutations have been identified in seven genes: two genes for autosomal dominant ("SPTLC1"…

  7. Early onset hereditary sensory autonomic neuropathy type I and not leprosy

    Directory of Open Access Journals (Sweden)

    Pande Sushil

    2009-01-01

    Full Text Available Hereditary sensory autonomic neuropathies (HSAN are rare forms of chronic neuropathies in children, which lead to severe complications like foot ulcers, mutilations, fractures and deformities. We report an eight years old female who presented with nonhealing perforating ulcer over anterior sole, resorption of terminal portion of right middle finger and hyperhidrosis over back since two years of age. Deep tendon reflexes were absent in lower legs but were preserved in upper limbs. Nerve conduction studies and nerve biopsy confirmed the diagnosis of HSAN, Type I. Early diagnosis of hereditary sensory neuropathy led to significant reduction in morbidity and hence improvement in the quality of life in our patient.

  8. Cardiac arrest after anesthetic management in a patient with hereditary sensory autonomic neuropathy type IV

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    Ergül Yakup

    2011-01-01

    Full Text Available Hereditary sensory autonomic neuropathy type IV is a rare disorder with an autosomal recessive transmission and characterized by self-mutilation due to a lack in pain and heat sensation. Recurrent hyperpyrexia and anhydrosis are seen in patients as a result of a lack of sweat gland innervation. Self-mutilation and insensitivity to pain result in orthopedic complications and patients undergone recurrent surgical interventions with anesthesia. However, these patients are prone to perioperative complications such as hyperthermia, hypothermia, and cardiac complications like bradycardia and hypotension. We report a 5-year-old boy with hereditary sensory autonomic neuropathy type IV, developing hyperpyrexia and cardiac arrest after anesthesia.

  9. New form of autosomal-recessive axonal hereditary sensory motor neuropathy.

    Science.gov (United States)

    Eckhardt, S M; Hicks, E M; Herron, B; Morrison, P J; Aicardi, J

    1998-09-01

    Two siblings, a male and a female, had severe axonal neuropathy and sideroblastic anemia. Despite a distinct clinical picture with areflexia, ataxia, hypotonia, optic atrophy, and progressive sensory neural hearing loss, no definite diagnosis could be reached and the older sibling died at 6 years of age of respiratory failure. It is proposed that the two affected siblings have a new form of autosomal-recessive axonal hereditary sensory motor neuropathy.

  10. Painless ulcers and fissures of toes: Hereditary sensory neuropathy, not leprosy

    Directory of Open Access Journals (Sweden)

    Angoori Gnaneshwar Rao

    2016-01-01

    Full Text Available Hereditary sensory neuropathies (HSN are rare genetically determined neuropathies. They often manifest as painless injuries in children. We present HSN in a 5-year-old boy who presented with recurrent fissuring and ulceration involving both great toes.

  11. Genetics Home Reference: hereditary sensory neuropathy type IA

    Science.gov (United States)

    ... the sensory abnormalities can affect the hands, arms, shoulders, joints, and abdomen. Affected individuals may also experience muscle wasting and weakness as they get older. Weakness in the ankle ...

  12. Ataxic hemiparesis: neurophysiological analysis by cerebellar transcranial magnetic stimulation.

    Science.gov (United States)

    Kikuchi, Saeko; Mochizuki, Hitoshi; Moriya, Arata; Nakatani-Enomoto, Setsu; Nakamura, Koichiro; Hanajima, Ritsuko; Ugawa, Yoshikazu

    2012-03-01

    The aim of this study was to investigate physiological mechanisms underlying ataxia in patients with ataxic hemiparesis. Subjects were three patients with ataxic hemiparesis, whose responsible lesion was located at the posterior limb of internal capsule (case 1), thalamus (case 2), or pre- and post-central gyri (case 3). Paired-pulse transcranial magnetic stimulation (TMS) technique was used to evaluate connectivity between the cerebellum and contralateral motor cortex. The conditioning cerebellar stimulus was given over the cerebellum and the test stimulus over the primary motor cortex. We studied how the conditioning stimulus modulated motor evoked potentials (MEPs) to the cortical test stimulus. In non-ataxic limbs, the cerebellar stimulus normally suppressed cortical MEPs. In ataxic limbs, the cerebellar inhibition was not elicited in patients with a lesion at the posterior limb of internal capsule (case 1) or thalamus (case 2). In contrast, normal cerebellar inhibition was elicited in the ataxic limb in a patient with a lesion at sensori-motor cortex (case 3). Lesions at the internal capsule and thalamus involved the cerebello-thalamo-cortical pathways and reduced the cerebellar suppression effect. On the other hand, a lesion at the pre- and post-central gyri should affect cortico-pontine pathway but not involve the cerebello-thalamo-cortical pathways. This lack of cerebello-talamo-cortical pathway involvement may explain normal suppression in this patient. The cerebellar TMS method can differentiate cerebellar efferent ataxic hemiparesis from cerebellar afferent ataxic hemiparesis.

  13. Rehabilitation of Sensory Ataxic Acute Guillain-Barre Syndrome:A Case Study%感觉性共济失调型急性格林-巴利综合征康复治疗个案分析

    Institute of Scientific and Technical Information of China (English)

    李鑫; 陈颖蓓; 李奎

    2013-01-01

    Objective To observe the effect of comprehensive rehabilitation based on motor control on sensory-ataxic acute Guillain-Barre syndrome. Methods A patient with sensory-ataxic acute Guillain-Barre syndrome was treated with kinesitherapy based on motor con-trol, included proprioceptive neuromuscular facilitation, coordination training, functional training, balance training, as well as sensory stimu-lation on the end of arms and legs, recumbent cross trainer therapy and cycle therapy for 2 months. Results After treatment, the score of In-ternational Cooperative Ataxia Rating Scale (ICARS) decreased 36 points, activities of daily living increased 9 points, Berg Balance Scale increased 9 points, and modified Barthel Index increased 50 points. Conclusion The comprehensive rehabilitation based on motor control is effective on this patient, but more cases and systematic curative effect evaluation are needed.%目的:观察基于运动控制的综合康复治疗对1例共济失调型急性格林-巴利综合征患者的疗效。方法运用本体感觉神经肌肉促进技术、协调性训练、功能训练、平衡训练等基于运动控制的运动疗法以及四肢末端感觉刺激、四肢联动、压力循环治疗等感觉运动治疗对1例共济失调型急性格林-巴利综合征患者进行2个月的综合康复治疗。结果治疗2个月后,患者国际合作共济失调评定量表(ICARS)下降36分,日常生活活动分析评估表提高9分,Berg平衡量表提高9分,改良Barthel指数提高50分。结论基于运动控制的综合康复治疗对该例共济失调型急性格林-巴利综合征患者疗效显著,但尚需进行病例积累和系统化疗效评价。

  14. [Hereditary sensory and autonomic neuropathy type II A: early neurological and skeletal findings].

    Science.gov (United States)

    Esmer, C; Díaz Zambrano, S; Santos Díaz, M A; González Huerta, L M; Cuevas Covarrubias, S A; Bravo Oro, A

    2014-04-01

    The hereditary sensory and autonomic neuropathies are genetic disorders characterized by the loss of sensation including pain, tactile and temperature. Its clinical and molecular features vary widely; the symptoms may begin from birth or be noticed in the first or second decade, with different types of complications of trauma to the extremities such as ulcers, mutilations and acral amputations. They are classified into six groups from I to VI, determined by the abnormality in eleven genes leading to phenotypic variations in the age of onset and the presence or absence of dysautonomia signs. With the exception of type I, all are autosomal recessive. The type II of these neuropathies is characterized by insensitivity to pain, heat and proprioception. We describe three members of a Mexican family with WNK1 gene mutation that caused hereditary neuropathy IIA.

  15. Recent advances in the genetics of hereditary axonal sensory-motor neuropathies type 2.

    Science.gov (United States)

    Ajroud-Driss, Senda; Deng, Han-Xiang; Siddique, Teepu

    2011-06-01

    Hereditary axonal motor and sensory neuropathies or Charcot-Marie-Tooth disease type 2 (CMT2) are characterized clinically by distal muscle weakness and atrophy, sensory loss, and foot deformities. Conduction velocities are usually in the normal range or mildly slowed. The majority of CMT2 are autosomal-dominant but autosomal-recessive forms have been described. The number of genes associated with CMT2 have significantly increased in the past decade, with the gene causing CMT2C/SPSMA being the last one discovered. More than 10 genes are now associated with different subtypes of CMT2, which are classified from CMT2A to CMT2N. These genes have distinct functions, but some appear to be involved in common biological pathways, therefore, providing important clues for understanding the pathogenic mechanism of these heterogeneous disorders.

  16. Pulmonary function in patients with hereditary motor and sensory neuropathy: a comparison of patients with and without spinal deformity.

    Science.gov (United States)

    Horacek, Ondrej; Chlumsky, Jan; Mazanec, Radim; Kolar, Pavel; Andel, Ross; Kobesova, Alena

    2012-12-01

    We assessed pulmonary function in hereditary motor and sensory neuropathy. Fourteen neuropathy patients without spinal deformity (group 1), 14 with spinal deformity (group 2), and 16 individuals with idiopathic spinal deformity (group 3) matched to group 2 for age, height and Cobb angle, were included. Hereditary motor and sensory neuropathy severity was measured with Charcot-Marie-Tooth Neuropathy Score. All participants exhibited mild decrease in maximal inspiratory pressure at the mouth. One-way analysis of variance yielded significant main effects for lung volumes - slow vital capacity, forced expiratory volume in 1s, and total lung capacity (p'sSlow vital capacity and total lung capacity correlated with maximal inspiratory pressure at the mouth in group 2, whereas slow vital capacity correlated with muscle work in group 3 (p's<.05). Decreased lung volume may be due to impaired respiratory muscle strength in hereditary motor and sensory neuropathy with spinal deformity and due to spinal deformity in idiopathic patients.

  17. Three cousins with chronic foot ulcers from late-onset hereditary sensory and autonomic neuropathies type 2 (HSAN2).

    Science.gov (United States)

    Aghaei, Shahin; Pakmanesh, Kambiz

    2006-02-28

    The hereditary sensory and autonomic neuropathies (HSAN) are a group of rare disorders characterized by prominent sensory and autonomic neuropathy without motor involvement. We report three male cousins with chronic foot ulcers, all were affected with late-onset HSAN type 2 (HSAN2). In view of the history of consanguinity and male sex, X-linked recessive transmission was likely in our patients. According to the authors' knowledge this is the first report of HSAN2 from Iran.

  18. Hereditary sensory and autonomic neuropathy type V: Report of a rare case

    Directory of Open Access Journals (Sweden)

    Ritesh Kalaskar

    2015-01-01

    Full Text Available Hereditary sensory and autonomic neuropathy (HSAN type V is a rare inherited disease caused by a mutation in the neurotrophic tyrosine kinase receptor, type 1 gene located on chromosome 1 (1q21-q22. It is characterized by pain insensitivity, partial anhydrosis without mental retardation and unimpaired touch and pressure sensitivity. Self-mutilation injury involving the teeth, lips, tongue, ears, eyes, nose, and fingers are invariable feature of this disorder. The purpose of this paper was to discuss the diagnosis and oral management of 18-month-old girl with HSAN type V, having typical oral manifestation of bitten tongue and auto-extraction of primary teeth. Modified bite guard was given to the patient to prevent further self-mutilating injuries to the tongue.

  19. Sporadic hereditary motor and sensory neuropathies: Advances in the diagnosis using next generation sequencing technology.

    Science.gov (United States)

    Fallerini, Chiara; Carignani, Giulia; Capoccitti, Giorgio; Federico, Antonio; Rufa, Alessandra; Pinto, Anna Maria; Rizzo, Caterina Lo; Rossi, Alessandro; Mari, Francesca; Mencarelli, Maria Antonietta; Giannini, Fabio; Renieri, Alessandra

    2015-12-15

    Hereditary motor and sensory neuropathies (HMSN) are genetically heterogeneous disorders affecting peripheral motor and sensory functions. Many different pathogenic variants in several genes involved in the demyelinating, the axonal and the intermediate HMSN forms have been identified, for which all inheritance patterns have been described. The mutation screening currently available is based on Sanger sequencing and is time-consuming and relatively expensive due to the high number of genes involved and to the absence of mutational hot spots. To overcome these limitations, we have designed a custom panel for simultaneous sequencing of 28 HMSN-related genes. We have applied this panel to three representative patients with variable HMSN phenotype and uncertain diagnostic classifications. Using our NGS platform we rapidly identified three already described pathogenic heterozygous variants in MFN2, MPZ and DNM2 genes. Here we show that our pre-custom platform allows a fast, specific and low-cost diagnosis in sporadic HMSN cases. This prompt diagnosis is useful for providing a well-timed treatment, establishing a recurrence risk and preventing further investigations poorly tolerated by patients and expensive for the health system. Importantly, our study illustrates the utility and successful application of NGS to mutation screening of a Mendelian disorder with extreme locus heterogeneity.

  20. Molecular pathogenesis, experimental therapy and genetic counseling in hereditary sensory neuropathies.

    Science.gov (United States)

    Mroczek, Magdalena; Kabzińska, Dagmara; Kochański, Andrzej

    2015-01-01

    Hereditary sensory and autonomic neuropathies (HSANs) represent a group of heritable peripheral nerve disorders usually taking a severe clinical course. HSAN-affected patients manifest with deep, poorly-healing ulcerations of the feet and hands. To date no definitive cure for HSANs has been developed and the molecular pathology of these disorders is complex. The aim of this review is therefore to present recent findings in terms of HSAN molecular pathogenesis. So far, mutations in 12 genes coding for different proteins have been reported in association with HSAN and the molecular pathogenesis has been elucidated in HSAN1a, HSAN4 and HSAN5. The genes involved in molecular pathogenesis of HSAN code for a wide spectrum of proteins from enzymes to specific nerve growth factors. As far as HSAN1a is concerned, the enhanced understanding has given rise to achievements in experimental therapy particularly in respect to disease models. Despite a rapid progress in studies on the molecular background of HSAN, numerous loci and genes remain still to be discovered.

  1. Hereditary motor and sensory neuropathies or Charcot-Marie-Tooth diseases: an update.

    Science.gov (United States)

    Tazir, Meriem; Hamadouche, Tarik; Nouioua, Sonia; Mathis, Stephane; Vallat, Jean-Michel

    2014-12-15

    Hereditary motor and sensory neuropathies (HMSN) or Charcot-Marie-Tooth (CMT) diseases are the most common degenerative disorders of the peripheral nervous system. However, the frequency of the different subtypes varies within distinct populations. Although more than seventy clinical and genetic forms are known to date, more than 80% of CMT patients in Western countries have genetic abnormalities associated with PMP22, MPZ, MFN2 and GJB1. Given the considerable genetic heterogeneity of CMT, we emphasize the interest of both clinical and pathological specific features such that focused genetic testing could be performed. In this regard, peripheral nerve lesions in GDAP1 mutations (AR CMT1A), such as mitochondrial abnormalities, have been newly demonstrated. Otherwise, while demyelinating autosomal recessive CMT used to be classified as CMT4 (A, B, C …), we propose a simplified classification such as AR CMT1 (A, B, C …), and AR CMT2 for axonal forms. Also, we stress that next generation sequencing techniques, now considered to be the most efficient methods of genetic testing in CMT, will be helpful in molecular diagnosis and research of new genes involved. Finally, while no effective therapy is known to date, ongoing new therapeutic trials such as PXT3003 (a low dose combination of the three already approved drugs baclofen, naltrexone, and D-sorbitol) give hopes for potential curative treatment.

  2. Genetics of hereditary motor and sensory neuropathy and the Costa Rican contribution

    Directory of Open Access Journals (Sweden)

    Alejandro Leal

    2004-09-01

    Full Text Available Hereditary motor and sensory neuropathy (HMSN or Charcot-Marie-Tooth disease (CMT is the most common hereditary illness of the peripheral nervous system. The genetics and the physiopathological aspects of the disease clarified until know, are here summarized. More than twenty genes and ten additional loci have been related with HMSN. These findings contribute to understand the metabolism of peripheral nerves and give the basis for molecular diagnostics and future therapy. Several Costa Rican families with CMT have been identified, specially with axonal forms. Two families present mutations in the myelin protein zero gene (MPZ. In addition, linkage have been found between the disease and locus 19q13.3 in an extended family, and a mutation segregating with the disease is present in a candidate gene of the critical interval. Costa Rica has several advantages for genetical studies, that can contribute importantly in the generation of knowledge in the neurogenetical field. Rev. Biol. Trop. 52(3: 475-483. Epub 2004 Dic 15.El grupo de neuropatías motoras y sensoriales hereditarias (HMSN o enfermedad de Charcot-Marie-Tooth (CMT es el padecimiento hereditario más común del sistema nervioso periférico. El propósito de este trabajo es resumir los aspectos genéticos y fisiopatológicos más actuales de esta enfermedad. Más de veinte genes y diez loci adicionales han sido relacionados con HMSN. Estos hallazgos han contribuido con la comprensión del metabolismo de los nervios periféricos y sirven de base para el diagnóstico molecular y el diseño de terapias. Diversas familias costarricenses con CMT han sido identificadas: dos de ellas presentan mutaciones en el gen que codifica por la mielina proteína cero (MPZ. Además, un análisis de ligamiento localizó el gen que causa una forma axonal de la enfermedad en el cromosoma 19q13.3 en una extensa familia; también se detectó en esa región una mutación que co-segrega con la enfermedad y que

  3. Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort.

    LENUS (Irish Health Repository)

    Davidson, G L

    2012-08-01

    The hereditary sensory and autonomic neuropathies (HSAN, also known as the hereditary sensory neuropathies) are a clinically and genetically heterogeneous group of disorders, characterised by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. To date, mutations in twelve genes have been identified as causing HSAN. To study the frequency of mutations in these genes and the associated phenotypes, we screened 140 index patients in our inherited neuropathy cohort with a clinical diagnosis of HSAN for mutations in the coding regions of SPTLC1, RAB7, WNK1\\/HSN2, FAM134B, NTRK1 (TRKA) and NGFB. We identified 25 index patients with mutations in six genes associated with HSAN (SPTLC1, RAB7, WNK1\\/HSN2, FAM134B, NTRK1 and NGFB); 20 of which appear to be pathogenic giving an overall mutation frequency of 14.3%. Mutations in the known genes for HSAN are rare suggesting that further HSAN genes are yet to be identified. The p.Cys133Trp mutation in SPTLC1 is the most common cause of HSAN in the UK population and should be screened first in all patients with sporadic or autosomal dominant HSAN.

  4. Perceptual Ratings of Subgroups of Ataxic Dysarthria

    Science.gov (United States)

    Spencer, Kristie A.; France, Ashley A.

    2016-01-01

    Background: The speech characteristics of ataxic dysarthria are known to be quite diverse. The varied presentation of this dysarthria challenges researchers and clinicians alike, and brings into question whether it is a single entity. While the possibility of subtypes of ataxic dysarthria has been suggested, the nature of these putative groups…

  5. Misclassification and linkage of hereditary sensory and autonomic neuropathy type 1 as Charcot-Marie-Tooth disease, Type 2B

    Energy Technology Data Exchange (ETDEWEB)

    Vance, J.M.; Speer, M.C.; Stajich, J.M. [Duke Univ. Medical Center, Durham, NC (United States)

    1996-07-01

    Recently Kwon et al. published in the Journal their work describing linkage of a single large family with an inherited axonal neuropathy to chromosome 3, which they suggest is a second locus for Charcot-Marie-Tooth (CMT) type 2 and subsequently named {open_quotes}CMT2B.{close_quotes} We think that the diagnostic classification of this family as CMT2 is incorrect, since the subjects have a severe sensory neuropathy that fits within the hereditary sensory and autonomic neuropathy (HSAN) type 1 classification of Dyck (1993). Abnormal sensory findings in CMT2 separate it from distal spinal muscular atrophy but are a minor component of clinical symptoms in most CMT patients, as CMT is primarily a motor neuropathy. When Kwon et al. state that {open_quotes}all [patients] had characteristic findings in their physical examinations, including... evidence of foot sores that were slow to heal, or amputated limbs related to the poorly healing foot ulcers,{close_quotes} it suggests that a different diagnosis is more appropriate. In our experience collecting data on >950 individuals in >60 CMT1, CMT2, CMTX and CMT4 families, we have not seen foot ulcers, osteomyelitis, or amputations. Ulcerations leading to osteomyelitis and amputations are usually associated with severe sensory neuropathies. 16 refs., 1 tab.

  6. ORAL MANIFESTATIONS AND PROSTHETIC REHABILITATION IN HEREDITARY SENSORY AND AUTONOMIC NEUROPATHY (HSANTYPE IV:A CASE REPORT*

    Directory of Open Access Journals (Sweden)

    Duygu OFLUOĞLU

    2016-04-01

    Full Text Available Hereditary sensory and autonomic neuropathies (HSAN are rare genetic syndromes of unknown etiology. They are seen in early childhood and are categorized into six different types by their symptoms. HSAN type 4 demonstrates autosomal recessive transmission pattern, with such major characteristics as loss of sense of pain, self-mutilation, anhydrosis and mental retardation. Sympathetic innervations are deficient despite the existence of sweat glands. Sufferers are hypotonic without any tendon reflexes, and neuro-motor development is retarded. In some cases tactile sensation and vibration may be intact. Biting injuries due to lack of pain sensation cause laceration, ulceration and scarring of the tongue, lips and other parts of oral mucosa. Tooth luxation and severe dental attrition have been observed. This case report presents oral and dental findings, surgical treatments and prosthetic rehabilitation of an 11- year-old boy with HSAN type 4.

  7. Hereditary motor and sensory neuropathy, caused by mutations in the NEFL gene in a family from Karachaevo-Cherkessia

    Directory of Open Access Journals (Sweden)

    E. L. Dadali

    2016-01-01

    Full Text Available The clinical and genetic features of hereditary motor and sensory neuropathy (HMSN; Charcot–Marie–Tooth disease, CMT caused by newly identified missense mutation s.65G>T (p.Pro22His in NEFL gene located on the chromosome 8р21.2 are described. The disease was diagnosed in a large family from Ust-Dzhegutinsky district of the Karachay-Cherkess Republic with the segregation of the disease in four generations. The prevalence of the HMSN in that district was found to be 1:4340 persons, including 1:3376 among Karachays. The clinical picture of the disease was characterized by onset at the age of 11–14 years, weakness in foot muscles and steppage gait. The specific features in the majority of patients were the absence of major sensory disturbances, as well as long-term preserved distal arm muscles. Nerve conduction velocity in the median nerve varied from 30 to 42 m/s, which corresponds to values in patients with CMT2E, previously described.

  8. Hereditary motor and sensory neuropathies: Understanding molecular pathogenesis could lead to future treatment strategies.

    Science.gov (United States)

    Jerath, Nivedita U; Shy, Michael E

    2015-04-01

    Inherited peripheral neuropathies, like many other degenerative disorders, have been challenging to treat. At this point, there is little specific therapy for the inherited neuropathies other than genetic counseling as well as symptomatic treatment and rehabilitation. In the past, ascorbic acid, progesterone antagonists, and subcutaneous neurotrophin-3 (NT3) injections have demonstrated improvement in animal models of CMT 1A, the most common inherited neuropathy, but have failed to translate any effect in humans. Given the difficulty in treatment, it is important to understand the molecular pathogenesis of hereditary neuropathies in order to strategize potential future therapies. The hereditary neuropathies are in an era of molecular insight and over the past 20 years, more than 78 subtypes of Charcot Marie Tooth disease (CMT) have been identified and extensively studied to understand the biological pathways in greater detail. Next generation molecular sequencing has also improved the diagnosis as well as the understanding of CMT. A greater understanding of the molecular pathways will help pave the way to future therapeutics of CMT. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.

  9. Complexity of the Hereditary Motor and Sensory Neuropathies: Clinical and Cellular Characterization of the MPZ p.D90E Mutation.

    Science.gov (United States)

    Lupo, Vincenzo; Pascual-Pascual, Samuel I; Sancho, Paula; Calpena, Eduardo; Gutiérrez-Molina, Manuel; Mateo-Martínez, Gonzalo; Espinós, Carmen; Arriola-Pereda, Gema

    2015-10-01

    Early-onset hereditary motor and sensory neuropathies are rare diseases representing a broad clinical and genetic spectrum. Without a notable familial history, the clinical diagnosis is complicated because acquired causes of peripheral neuropathy, such as inflammatory neuropathies, neuropathies with toxic causes, and nutritional deficiencies, must be considered. We examined the clinical, electrophysiological, and pathologic manifestations of a boy with an initial diagnosis of chronic inflammatory demyelinating polyneuropathy. The progression of the disease despite treatment led to a suspicion of hereditary motor and sensory neuropathy. Genetic testing revealed the presence of the MPZ p.D90E mutation in heterozygosis. To clarify the pathogenicity of this mutation and achieve a conclusive diagnosis, we investigated the MPZ p.D90E mutation through in silico and cellular approaches. This study broadens the clinical phenotype of hereditary motor and sensory neuropathy due to MPZ mutation and emphasises the difficulty of achieving an accurate genetic diagnosis in a sporadic patient to provide an appropriate pharmacologic treatment.

  10. [A review of the oro-dento-facial characteristics of hereditary sensory and autonomic neuropathy type III (familial dysautonomia)].

    Science.gov (United States)

    Mass, E

    2013-01-01

    The oro-dento-facial features and dysfunction of children with hereditary sensory and autonomic neuropathy type Ill, known as familial dysautonomia or Riley-Day syndrome, was first described in the scientific literature in 1949. They include dental trauma; dental and soft tissue self-mutilation; normal dental age; normal sequence and timing of eruption and exfoliation of teeth; smaller tooth size; different and disproportional tooth components; normal alveolar bone height; small jaws, mild crowding, and malocclusions. These persons have craniofacial morphology that is different from accepted norms but they resemble norms of their ethnic origin. The subjects can have gray, pale, shiny faces with an asymmetric suffering expression; frontal bossing, with eventual hypertelorism and narrow lips; a low caries rate; drooling, and hypersalivation. They can have changes in salivary composition and content, which influences plaque and calculus and increases the risk of gingival and periodontal diseases. They also have difficulty in controlling oral muscles; a progressive decrease in number of tongue fungiform papillae, accompanied by lack of taste buds; and specific dysgeusia, but a normal sense of smell.

  11. A review of the oro-dento-facial characteristics of hereditary sensory and autonomic neuropathy type III (familial dysautonomia).

    Science.gov (United States)

    Mass, Eliyahu

    2012-01-01

    The oro-dento-facial features and dysfunction of children with hereditary sensory and autonomic neuropathy type III, known as familial dysautonomia or Riley-Day syndrome, was first described in the scientific literature in 1949. They include dental trauma; dental and soft tissue self-mutilation; normal dental age; normal sequence and timing of eruption and exfoliation of teeth; smaller tooth size; different and disproportional tooth components; normal alveolar bone height; small jaws, mild crowding, and malocclusions. These persons have craniofacial morphology that is different from accepted norms but they resemble norms of their ethnic origin. The subjects can have gray, pale, shiny faces with an asymmetric suffering expression; frontal bossing, with eventual hypertelorism and narrow lips; a low-caries rate; drooling, and hypersalivation. They can have changes in salivary composition and content, which influences plaque and calculus and increases the risk of gingival and periodontal diseases. They also have difficulty in controlling oral muscles; a progressive decrease in number of tongue fungiform papillae, accompanied by lack of taste buds; and specific dysgeusia, but a normal sense of smell.

  12. Pathogenic mutations and sequence variants within mitofusin 2 gene in Polish patients with different hereditary motor-sensory neuropathies.

    Science.gov (United States)

    Kotruchow, Katarzyna; Kabzińska, Dagmara; Kochański, Andrzej

    2015-01-01

    At the time of its first description in 2004, MFN2 was considered the most frequently mutated gene in hereditary motor and sensory neuropathy type 2 (HMSN 2). However recent studies have shown that the frequency of MFN2 gene mutations in HMSN II patients is surprisingly low. To date, no systematic studies devoted to HMSN IIa in Poland have been carried out. In this study, we searched for MFN2 gene mutations in Polish patients representing the population of nearly 40 million. We decided to include a wide spectrum of clinical phenotypes in the study, proving able to detect, in a group of 67 affected patients: 1) 3 pathogenic mutations; 2) 3 sequence variants of unknown pathogenic status; 3) 9 rare MFN2 gene sequence variants; 4) 6 common polymorphisms. The frequency of MFN2 gene mutations in the whole group of patients is 4.5%. Due to the high frequency of MFN2 gene sequence variants within single patients we could not definitely exclude the cumulative effect of these contributing to the HMSN II phenotype. The MFN2 gene should therefore be considered in Polish HMSN II patients, though it is still not possible to determine its position in HMSN II molecular diagnostics.

  13. [Developments in hereditary neuropathies].

    Science.gov (United States)

    Dubourg, O

    2012-12-01

    Hereditary sensorimotor neuropathies, or Charcot-Marie-Tooth disease (CMT) comprise a group of diseases with heterogeneous clinical, electrophysiological and genetic expression. They are classified by the mode of inheritance (autosomal dominant, X-linked dominant, autosomal recessive) and their electrophysiological characteristics taking into account the speed of motor conduction of the median nerve (demyelinating, intermediary and axonal forms). Certain purely motor forms are called spinal CMT or hereditary distal motor neuropathy, or distal spinal amyotrophy. CMT involving an important sensorial component, trophic disorders, or signs of dysautonomia are included in the classification of hereditary sensory and autonomic neuropathies.

  14. Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the Study of Canadian Genetic Isolates.

    Science.gov (United States)

    Lafreniere, Ronald G; MacDonald, Marcia L E; Dube, Marie-Pierre; MacFarlane, Julie; O'Driscoll, Mary; Brais, Bernard; Meilleur, Sebastien; Brinkman, Ryan R; Dadivas, Owen; Pape, Terry; Platon, Christele; Radomski, Chris; Risler, Jenni; Thompson, Jay; Guerra-Escobio, Ana-Maria; Davar, Gudarz; Breakefield, Xandra O; Pimstone, Simon N; Green, Roger; Pryse-Phillips, William; Goldberg, Y Paul; Younghusband, H Banfield; Hayden, Michael R; Sherrington, Robin; Rouleau, Guy A; Samuels, Mark E

    2004-05-01

    Hereditary sensory and autonomic neuropathy (HSAN) type II is an autosomal recessive disorder characterized by impairment of pain, temperature, and touch sensation owing to reduction or absence of peripheral sensory neurons. We identified two large pedigrees segregating the disorder in an isolated population living in Newfoundland and performed a 5-cM genome scan. Linkage analysis identified a locus mapping to 12p13.33 with a maximum LOD score of 8.4. Haplotype sharing defined a candidate interval of 1.06 Mb containing all or part of seven annotated genes, sequencing of which failed to detect causative mutations. Comparative genomics revealed a conserved ORF corresponding to a novel gene in which we found three different truncating mutations among five families including patients from rural Quebec and Nova Scotia. This gene, termed "HSN2," consists of a single exon located within intron 8 of the PRKWNK1 gene and is transcribed from the same strand. The HSN2 protein may play a role in the development and/or maintenance of peripheral sensory neurons or their supporting Schwann cells.

  15. Isolated thalamic tuberculoma presenting as ataxic hemiparesis

    Science.gov (United States)

    Sahu, Ritesh; Patil, Tushar B; Kori, Prakash; Shukla, Rakesh

    2013-01-01

    Lacunar syndrome is a neurodeficit secondary to a deep cerebral lesion, usually because of microatheroma of small arteries. Ataxic hemiparesis (AH) is a lacunar syndrome with unilateral pyramidal weakness and ipsilateral ataxia. Thalamic tuberculoma, as a cause of AH, has not been previously described in the literature. We describe an elderly man who presented with left hemiparesis and ipsilateral ataxia. Clinical examination revealed upper motor neuron left facial paresis and left-sided hemiparesis. The patient had incoordination in left upper and lower limbs. Mantoux test was positive and erythrocyte sedimentation rate was elevated. MRI of brain showed a conglomerated hypointense lesion in the right thalamus with a peripheral hyperintensity on T1-weighted imaging and a hyperintense lesion in T2-weighted imaging with significant perilesional oedema, suggesting a tuberculoma. The patient was treated with antitubercular therapy and was symptomatically better at the 9 months follow-up. PMID:23580686

  16. Vitamin B nutrition in the Nigerian tropical ataxic neuropathy.

    OpenAIRE

    1985-01-01

    Assessment of nutritional status of vitamin B components by plasma or blood levels indicated riboflavin deficiency and possibly thiamine deficiency in Nigerian patients who suffered from tropical ataxic neuropathy and neurologically normal Nigerians who subsisted on predominant cassava diet. Serum levels of folate, niacin, pyridoxine and panthothenic acid were normal. Vitamin deficiencies probably are minor factors, if any, in the pathogenesis of tropical ataxic neuropathy in Nigerians.

  17. Taking pain out of NGF: a "painless" NGF mutant, linked to hereditary sensory autonomic neuropathy type V, with full neurotrophic activity.

    Directory of Open Access Journals (Sweden)

    Simona Capsoni

    Full Text Available During adulthood, the neurotrophin Nerve Growth Factor (NGF sensitizes nociceptors, thereby increasing the response to noxious stimuli. The relationship between NGF and pain is supported by genetic evidence: mutations in the NGF TrkA receptor in patients affected by an hereditary rare disease (Hereditary Sensory and Autonomic Neuropathy type IV, HSAN IV determine a congenital form of severe pain insensitivity, with mental retardation, while a mutation in NGFB gene, leading to the aminoacid substitution R100W in mature NGF, determines a similar loss of pain perception, without overt cognitive neurological defects (HSAN V. The R100W mutation provokes a reduced processing of proNGF to mature NGF in cultured cells and a higher percentage of neurotrophin secreted is in the proNGF form. Moreover, using Surface Plasmon Resonance we showed that the R100W mutation does not affect NGF binding to TrkA, while it abolishes NGF binding to p75NTR receptors. However, it remains to be clarified whether the major impact of the mutation is on the biological function of proNGF or of mature NGF and to what extent the effects of the R100W mutation on the HSAN V clinical phenotype are developmental, or whether they reflect an impaired effectiveness of NGF to regulate and mediate nociceptive transmission in adult sensory neurons. Here we show that the R100 mutation selectively alters some of the signaling pathways activated downstream of TrkA NGF receptors. NGFR100 mutants maintain identical neurotrophic and neuroprotective properties in a variety of cell assays, while displaying a significantly reduced pain-inducing activity in vivo (n = 8-10 mice/group. We also show that proNGF has a significantly reduced nociceptive activity, with respect to NGF. Both sets of results jointly contribute to elucidating the mechanisms underlying the clinical HSAN V manifestations, and to clarifying which receptors and intracellular signaling cascades participate in the pain

  18. Hereditary motor and sensory neuropathy with congenital glaucoma: report on a family Neuropatia hereditária sensitivo-motora com glaucoma congênito: descrição de uma família

    OpenAIRE

    Arruda,Walter O.; COMERLATO,ENIO A.; Scola,Rosana H.; Silvado,Carlos E.S.; Lineu C. Werneck

    1999-01-01

    We report three siblings of a family with hereditary motor and sensory polyneuropathy (HMSN) and buphthalmos. Electrophysiological studies showed a demyelinating neuropathy and pathological findings showed severe loss of myelinated fibers (MF), thin myelin sheaths and myelin infoldings in a few remaining MF. The presumed mode of inheritance is autosomal recessive. This family probably represents an unique form of CMT4 that may be related to one of the congenital glaucoma genic locus, particul...

  19. Report of Two Siblings with Hereditary Sensory Neuropathy%姐弟2人同患遗传性感觉神经根神经病报告

    Institute of Scientific and Technical Information of China (English)

    严亮; 熊龙; 汤晓正

    2012-01-01

      目的探讨遗传性感觉神经根神经病(hereditary radicular sensory neuropathy ,HSN)的诊断和治疗。方法对同患HSN的姐弟2人的临床资料进行分析。结果患者父母为近亲结婚,青春期后隐匿起病,以足部无痛性毁损性溃疡为主,病程长,进展缓慢,虽不会影响寿命,但会遗留残疾,肢端浅感觉减退呈“手套”和“袜套”型,后期渐累及手部。治疗主要是避免感染及损伤,加强护理,对症处理,严重者可截肢。结论HSN是一种极为罕见的遗传性周围神经系统疾病,目前尚无有效治疗方法,婚前的遗传咨询可预防此病的发生。

  20. Hereditary spherocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Weed, R.I.

    1975-10-01

    Studies of the clinical features of hereditary spherocytosis since 1871 and laboratory investigation of the cellular abnormalities since 1940 have led to the characterization of hereditary spherocytosis as a prime example of a Mendelian dominant, genetically determined disorder of the erythrocyte membrane. This review of hereditary spherocytosis emphasizes the contributions of Dr. Lawrence Young and many others to our present understanding of the disease and discusses current studies of the protein abnormality in the membrane of hereditary spherocytes.

  1. Salvage procedures in lower-extremity trauma in a child with hereditary motor and sensory neuropathy type I: a case report

    Directory of Open Access Journals (Sweden)

    Gothner Martin

    2012-09-01

    Full Text Available Abstract Introduction Fractures of the lower extremity are a common type of childhood injury and many can be treated without surgery. Dislocated and open fractures are an indication for fracture stabilization via either intramedullary nailing or, in the case of complicated fractures, external fixation. But if complications are likely because of diseases and disabilities (for example, a neuropathy that can complicate the post-operative procedure and rehabilitation, what options does one have? Case presentation We report a nine-year-old Caucasian girl who had hereditary motor and sensory neuropathy type I and who was admitted with a grade I open tibia fracture after a fall from a small height. Plain radiographs showed a dislocated tibia and fibula fracture. An open reduction with internal fixation with a compression plate osteosynthesis was performed, and soft tissue debridement combined with an external fixateur was undertaken. Three months later, she was re-admitted with localized swelling and signs of a local soft tissue infection in the middle of her tibia. Plain radiographs showed a non-union of the tibia fracture, and microbiological analysis confirmed a wound infection with cefuroxime-sensitive Staphylococcus aureus. Because of the non-union, the osteosynthesis was replaced with an Ilizarov external fixateur, and appropriate antibiotic therapy was initiated. Four months after the initial accident, the fracture was consolidated and we removed the external fixateur. Conclusions If there is a pre-existing neuropathy and if disease makes it difficult for a child to follow all post-operative instructions, salvage procedures should be kept in mind in case of complications. There are multiple therapeutic options, including osteosynthesis, intramedullary nailing systems, cast therapy, or an external fixateur like the Ilizarov or Taylor spatial frame system. The initial use of an external fixateur such as an Ilizarov or Taylor spatial frame in

  2. Ataxic dysarthria: treatment sequences based on intelligibility and prosodic considerations.

    Science.gov (United States)

    Yorkston, K M; Beukelman, D R

    1981-11-01

    Treatment programs of four improving ataxic dysarthric speakers are reviewed. Treatment sequences were based on two overall measures of speech performance-intelligibility and prosody. Increases in intelligibility were initially achieved by control of speaking rate. A hierarchy of rate control strategies, ranging from a rigid imposition of rate through thythmic cueing to self-monitored rate control is discussed. As speakers improved their monitoring skills, a compromise was made between intelligibility and rate. Normal prosodic patterns were not achieved by the ataxic speakers due to difficulty in precisely coordinating the subtle fundamental frequency, loudness and timing adjustments needed to signal stress. Three of the four subjects were taught to use only durational adjustments to signal stress. In this way, they were able to achieve stress on targeted words consistently and minimize bizarreness which resulted from sweeping changes in fundamental frequency and bursts of loudness. The need for further clinically oriented research is discussed.

  3. Neuropatia sensitiva e autonômica herditátia tipo II: a propósito de dois casos Hereditary sensory and autonomic neuropathy type 2: two cases report

    Directory of Open Access Journals (Sweden)

    Wilson Luiz Sanvito

    2003-09-01

    Full Text Available Dois casos de neuropatia sensitiva e autonômica hereditária do tipo 2 são descritos. Este tipo de neuropatia faz parte de um grupo constituído por cinco entidades diferentes. A sistematização destas neuropatias depende de múltiplos critérios como idade de início, aspectos genéticos, manifestações clínicas, aspectos eletroneuromiográficos e patológicos. Neste relato descrevemos dois irmãos com 27 e 35 anos de idade que foram acompanhados em nosso Serviço, com quadro de insensibilidade à dor e conseqüentes deformidades de membros e distúrbios sensitivo-tróficos. Para estes pacientes foi definido o diagnóstico de neuropatia sensitiva e autonômica hereditária do tipo 2, com modalidade de transmissão hereditária autossômica recessiva. A idade de início do quadro, os aspectos hereditários, as manifestações clínicas e os aspectos eletroneuromiográficos são analisados. O diagnóstico diferencial com outras neuropatias sensitivas hereditárias e adquiridas é considerado.Two cases of hereditary sensory and autonomic neuropathy type 2 are reported. This type of neuropathy is included in a group that consists of five different entities. The systematization of that neuropathies depends on multiple criteria such as age of beginning, genetic aspects, clinical manifestations, eletroneuromyographic and pathologic features. In this report we describe the cases in a family, two brothers, 27 and 35 years old that were observed in our department with pain insensibility and consequent sensitive-trophic disturbs and deformity of members. The diagnoses was defined as hereditary sensory and autonomic neuropathy type 2 and an inherited pattern recessive autossomic transmission was considered. The age of beginning, the hereditary aspects, the clinical manifestations and the eletroneuromyographic features are analysed. The differential diagnoses with other sensory hereditary and acquired neuropathies is emphasized.

  4. Temporal disruption of upper-limb anticipatory postural adjustments in cerebellar ataxic patients.

    Science.gov (United States)

    Bruttini, Carlo; Esposti, Roberto; Bolzoni, Francesco; Vanotti, Alessandra; Mariotti, Caterina; Cavallari, Paolo

    2015-01-01

    Voluntary movements induce postural perturbations, which are counteracted by anticipatory postural adjustments (APAs) that preserve body equilibrium. Little is known about the neural structures generating APAs, but several studies suggested a role of sensory-motor areas, basal ganglia, supplementary motor area and thalamus. However, the role of the cerebellum still remains an open question. The aim of this present paper is to shed further light on the role of cerebellum in APAs organization. Thus, APAs that stabilize the arm when the index finger is briskly flexed were recorded in 13 ataxic subjects (seven sporadic cases, four dominant ataxia type III and two autosomal recessive), presenting a slowly progressive cerebellar syndrome with four-limb dysmetria, and compared with those obtained in 13 healthy subjects. The pattern of postural activity was similar in the two groups [excitation in triceps and inhibition in biceps and anterior deltoid (AD)], but apparent modifications in timing were observed in all ataxic subjects in which, on average, triceps brachii excitation lagged the onset of the prime mover flexor digitorum superficialis by about 27 ms and biceps and AD inhibition were almost synchronous to it. Instead, in normal subjects, triceps onset was synchronous to the prime mover and biceps and AD anticipated it by about 40 ms. The observed disruption of the intra-limb APA organization confirms that the cerebellum is involved in APA control and, considering cerebellar subjects as a model of dysmetria, also supports the view that a proper APA chain may play a crucial role in refining movement metria.

  5. Sensory ataxia as a prominent clinical presentation in three families with mutations in CYP7B1.

    Science.gov (United States)

    Di Fabio, Roberto; Marcotulli, Christian; Tessa, Alessandra; Leonardi, Luca; Storti, Eugenia; Pierelli, Francesco; Santorelli, Filippo M; Casali, Carlo

    2014-04-01

    Pathogenic mutations in CYP7B1 account for SPG5, an autosomal recessive hereditary spastic paraplegia characterized by a complex phenotype including visual problems and cerebellar dysfunction. Sensory ataxia is not usually regarded as a typical clinical feature of SPG5. The purpose of this study was to describe six patients showing features of sensory ataxia as the prominent and/or initial symptoms of SPG5. Six patients from three distinct pedigrees (three women, three men; age 49.5 ± 18.2 years), all presenting gait unsteadiness and frequent falls since childhood, underwent clinical and molecular investigations. All showed marked sensory ataxic gait with positive Romberg's sign, as well as severely impaired position and vibration sense. Comparatively minor signs of pyramidal involvement were also detected. In four of the patients, brain MRI showed white matter hyperintensities on T2-weighted images. An already reported homozygous c.889A>G (p.T297A) mutation in SPG5/CYP7B1 was found in five patients from two families, whereas the remaining case harbored the novel c.250_251delC/p.L84Ffs*6 and c.266A>C/p.Y89S variants. Marked and enduring sensory ataxia can be a pivotal sign in SPG5, and expands the phenotypic spectrum associated with mutations in CYP7B1.

  6. [Hereditary peripheral neuropathies].

    Science.gov (United States)

    Vallat, Jean-Michel; Tazir, Mériem; Calvo, Judith; Funalot, Benoît

    2009-09-01

    Currently more than 30 genes are known to be responsible for genetically determined neuropathies. Charcot-Marie-Tooth (CMT) disease is the most frequent of these hereditary neuropathies, with a prevalence of 4.7 to 36 per 100 000. In its demyelinating forms (CMT1), approximately 70% of cases are associated with a duplication of the PMP22gene. In its axonal forms (CMT2), 10-20% of the cases may be associated with a mutation of the MFN2gene. For North African patients with recessive transmission, a mutation of the LMNA gene must be sought. It is essential to stress the great variability of the phenotype--clinical, electrophysiological, and histologic--between and within families. A detailed analysis of these criteria, together with consideration of ethnic origin, may guide the search for the causal mutation. Whether the case involves certainly hereditary transmission or a sporadic form, it is desirable to be able to examine the maximum number of the patient's kin, both clinically and electrophysiologically. The forms with recessive transmission usually have a very early onset and are more serious than the dominant forms. The early- and very early-onset forms of CMT are increasingly better distinguished: congenital hypomyelination neuropathy (mutations of PMP22, MPZ or EGR2), or more axonal forms, including SMARD1 (Spinal muscle atrophy with respiratory distress; mutations of IGHMBP2) and EOHMSN (Early-onset hereditary motor and sensory neuropathy; mutations of MFN2). The prevention of cutaneous (ulcerations), bone, and amputation complications is very important in patients with hereditary sensory and autonomic neuropathies, because of the severity of the sensory disorders.

  7. Therapeutic Intervention in a Case of Ataxic Dysarthria Associated with a History of Amateur Boxing

    Science.gov (United States)

    McMicken, Betty L.; Ostergren, Jennifer A.; Vento-Wilson, Margaret

    2011-01-01

    The goals of this study were to (a) describe the presenting features of ataxic dysarthria present in a participant with a long history of amateur boxing, (b) describe a novel application of behavioral principles in the treatment of this participant, and (c) discuss implications in the treatment of ataxic dysarthria secondary to boxing. The…

  8. Therapeutic Intervention in a Case of Ataxic Dysarthria Associated with a History of Amateur Boxing

    Science.gov (United States)

    McMicken, Betty L.; Ostergren, Jennifer A.; Vento-Wilson, Margaret

    2011-01-01

    The goals of this study were to (a) describe the presenting features of ataxic dysarthria present in a participant with a long history of amateur boxing, (b) describe a novel application of behavioral principles in the treatment of this participant, and (c) discuss implications in the treatment of ataxic dysarthria secondary to boxing. The…

  9. Hereditary neuropathies: An update.

    Science.gov (United States)

    Stojkovic, T

    2016-12-01

    Hereditary neuropathies are the most common inherited neuromuscular diseases. Charcot-Marie-Tooth (CMT) disease represents the most common form with an average prevalence ranging from 1/2500 to 1/1200, depending on the studies. To date and with the advances of the latest generation sequencing, more than 80 genes have been identified. Although the common clinical phenotype comprises a progressive distal muscle weakness and sensory loss, foot deformities and decreased or absent tendon reflexes, clinical and electrophysiological phenotypes exhibit great variability. Moreover, atypical phenotypes are arising, overlapping with spastic paraplegia, hereditary sensory neuropathies or amyotrophic lateral sclerosis. The causative genes are involved in various biological processes such as myelin development and maintenance, biosynthesis and degradation of proteins, neuronal structural maintenance, axonal transport, endocytosis, membrane dynamics, ion-channel function and the mitochondrial network. An accurate genetic diagnosis is important for appropriate genetic counselling and treatment options. Therapeutic advances, particularly small interfering RNA therapy, are encouraging in hereditary transthyretin amyloid neuropathy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. [Hereditary hemocromatosis].

    Science.gov (United States)

    Franchini, Massimo; Veneri, Dino

    2004-10-01

    Hereditary hemochromatosis is a disorder of iron metabolism characterized by a progressive tissue iron overload which leads to an irreversible organ damage if it is not treated timely. The recent developments in the field of molecular medicine have radically changed the physiopathology and the diagnosis of this disease. However, transferrin saturation and serum ferritin are still the most reliable tests for the detection of subjects with hereditary hemochromatosis. Therapeutic phlebotomy is the mainstay of the treatment of hereditary hemochromatosis. If phlebotomy is started before the onset of irreversible organ damages, the life expectancy of these patients is similar to that of normal population.

  11. Histology of hereditary neuralgic amyotrophy.

    NARCIS (Netherlands)

    Alfen, N. van; Gabreëls-Festen, A.A.W.M.; Laak, H.J. ter; Arts, W.F.M.; Gabreëls, F.J.M.; Engelen, B.G.M. van

    2005-01-01

    We report the findings in five muscle and three sural nerve biopsies, and in one postmortem plexus specimen, from six patients with hereditary neuralgic amyotrophy (HNA). We found that the sensory nerves are definitely involved in HNA despite the mainly motor symptoms, and that lesions in nerves and

  12. Hereditary pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Richard M Charnley

    2003-01-01

    Hereditary pancreatitis is an autosomal dominant condition,which results in recurrent attacks of acute pancreatitis,progressing to chronic pancreatitis often at a young age.The majority of patients with hereditary pancreatitis expressone of two mutations (R122H or N29I) in the cationictrypsinogen gene (PRSS1 gene). It has been hypothesisedthat one of these mutations, the R122H mutation causespancreatitis by altering a trypsin recognition site sopreventing deactivation of trypsin within the pancreas andprolonging its action, resulting in autodigestion. Families withthese two mutations have been identified in many countriesand there are also other rarer mutations, which have alsobeen linked to hereditary pancreatitis.Patients with hereditary pancreatitis present in the sameway as those with sporadic pancreatitis but at an earlierage. It is common for patients to remain undiagnosed formany years, particularly ifthey present with non-specificsymptoms. Hereditary pancreatitis should always beconsidered in patients who present with recurrent pancreatitiswith a family history of pancreatic disease. If patients withthe 2 common mutations are compared, those with theR122H mutation are more likely to present at a younger ageand are more likely to require surgical intervention than thosewith N29I. Hereditary pancreatitis carries a 40 % lifetimerisk of pancreatic cancer with those patients aged between50 to 70 being most at risk in whom screening tests maybecome important.

  13. Successful outcome in a twin pregnancy with hereditary motor and sensory neuropathy type –II complicated with heart disease and preclampsia superimposed on chronic hypertension

    Directory of Open Access Journals (Sweden)

    Debasmita Mondal

    2008-06-01

    Full Text Available Heridetary motor and sensory neuropathy (HMSN TYPE-2 reflects reduction in the number of primary motor and sensory neurons. The occurrence of this disease is rare in pregnancy but may be exaggerated in pregnancy leading to preeclampsia / eclampsia. Here is a 28 years old 2nd gravidae with twin pregnancy at 31 weeks hospitalized with HMSN TYPE-2 disease and was managed successfully with good feto maternal outcome

  14. A new unifying hypothesis for lathyrism, konzo and tropical ataxic neuropathy: nitriles are the causative agents.

    Science.gov (United States)

    Llorens, Jordi; Soler-Martín, Carla; Saldaña-Ruíz, Sandra; Cutillas, Blanca; Ambrosio, Santiago; Boadas-Vaello, Pere

    2011-03-01

    Konzo and lathyrism are associated with consumption of cassava and grass pea, respectively. Cassava consumption has also been associated with a third disease, tropical ataxic neuropathy (TAN). This review presents a new unifying hypothesis on the causative agents for these diseases: namely, that they are nitriles, compounds containing cyano groups. The diseases may be caused by different but similar nitriles through direct neurotoxic actions not mediated by systemic cyanide release. Both cassava and Lathyrus contain nitriles, and other unidentified nitriles can be generated during food processing or in the human body. Available data indicate that several small nitriles cause a variety of neurotoxic effects. In experimental animals, 3,3'-iminodipropionitrile (IDPN), allylnitrile and cis-crotononitrile cause sensory toxicity, whereas hexadienenitrile and trans-crotononitrile induce selective neuronal degeneration in discrete brain regions. IDPN also induces a neurofilamentous axonopathy, and dimethylaminopropionitrile is known to cause autonomic (genito-urinary) neurotoxicity in both humans and rodents. Some of these actions depend on metabolic bioactivation of the parental nitriles, and sex- and species-dependent differences in susceptibility have been recorded. Recently, neuronal degeneration has been found in rats exposed to acetone cyanohydrin. Taken together, the neurotoxic properties of nitriles make them excellent candidates as causative agents for konzo, lathyrism and TAN. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Hereditary Diffuse Gastric Cancer

    Science.gov (United States)

    ... Hereditary Diffuse Gastric Cancer Request Permissions Hereditary Diffuse Gastric Cancer Approved by the Cancer.Net Editorial Board , 11/2015 What is hereditary diffuse gastric cancer? Hereditary diffuse gastric cancer (HDGC) is an inherited ...

  16. Ataxic gait following total gastrectomy for gastric cancer

    Science.gov (United States)

    Hwang, Chang Ho; Park, Dong Jin; Kim, Gyu Yeol

    2016-01-01

    A 58-year-old woman, who had undergone total gastrectomy for early gastric cancer 9 years previously, visited the outpatient clinic complaining of progressive difficulty in walking for 15 d. Laboratory examinations showed macrocytic anemia and a decreased serum vitamin B12 concentration and increased serum concentrations of folate, vitamin E and copper. Magnetic resonance imaging showed multifocal high signal intensities along the posterior column of the cervical and thoracic spinal cord. Treatment consisted of intramuscular injections of vitamin B12 for 7 d, which increased her serum level of vitamin B12 to normal. This was followed by weekly intramuscular injections of vitamin B12 for another 2 wk and oral administration of vitamin B12 three times per day. After comprehensive rehabilitation for 4 wk, she showed sufficient improvements in strength and ataxic gait, enabling her to return to her normal daily activities. PMID:27729749

  17. Hereditary spherocytosis.

    Science.gov (United States)

    Iolascon, A; Avvisati, R A; Piscopo, C

    2010-09-01

    Hereditary spherocytosis is a common hemolytic disorder characterized by a defect or deficiency in one or more of the proteins composing red blood cell membrane. As a result, red blood cells have an abnormal shape, higher metabolic requirements, and are prematurely trapped and destroyed in the spleen. Hereditary spherocytosis, including the very mild or subclinical forms, is the most common cause of non-immune hemolytic anemia among people of Northern European ancestry, with a prevalence of approximately 1 in 2000. However very mild forms of the disease may be much more common. Hereditary spherocytosis is inherited in a dominant fashion in 75% of cases, whereas the remaining are truly recessive cases and de novo mutations. This review reports current concepts on red cell membrane structure and it will attempt to clarify molecular defects leading to spherocyte and their consequences.

  18. [Hereditary neuropathies].

    Science.gov (United States)

    Vallat, Jean-Michel; Calvo, Judith; Ghorab, Karima; Tazir, Meriem

    2008-11-15

    Although there are many human hereditary neuropathies, most of them with the exception of Charcot-Marie-Tooth disease or hereditary sensorimotor neuropathy, are rare. Irrespective of their type, the mode of transmission may be autosomal dominant or recessive, or X-linked. The most difficult to diagnose, however, are the sporadic forms. It is customary to distinguish the cases in which the neuropathy is the sole clinical expression from multisystemic diseases where neuropathy is one component of multi-organ involvement. The complexity and the multiplicity of genes involved and the lack of understanding of their exact functions hinder logical presentation of these hereditary neuropathies. For understandable technical reasons, the stage of specific treatment, namely the repair of the mutated gene, has yet to be attained.

  19. Hereditary angioedema

    DEFF Research Database (Denmark)

    Peterson, M P; Bygum, A

    2016-01-01

    We report a 64-year-old man who suffered from recurrent visible swelling attacks since the age of 20 as well as episodes with severe upper airway edema, resulting in 4 emergency tracheotomies. Eventually after 44 years he was diagnosed with hereditary angioedema (HAE) type II. The aims...

  20. Hereditary Angioedema

    DEFF Research Database (Denmark)

    Abdel-Karim, Omar; Dizdarevic, Adis; Bygum, Anette

    2014-01-01

    Hereditary angioedema is an inherited disease that causes periodic swelling attacks, which can be life threatening and have a major effect on a patient's life. Studies have shown that home therapy for angioedema reduces disease severity, leads to faster relief of symptoms, and improves quality...

  1. Function disability evaluation in hereditary motor and sensory neuropathy pediatric patients%遗传性运动感觉性神经病儿童功能障碍评估

    Institute of Scientific and Technical Information of China (English)

    侯池; 吕俊兰

    2014-01-01

    遗传性运动感觉性神经病是最常见的遗传性周围神经病,该病的特点为缓慢进展,肌无力及肌萎缩累及肢体近端及严重的足畸形可造成患者功能障碍.因为大多数患者在儿童期起病,所以,功能障碍的动态评估及规范化的治疗对改善患儿预后具有重要意义.%Hereditary motor and sensory neuropathy is the most common peripheral neuropathy.It is slowly progressive,proximal limb weakness and muscular dystrophy and severe foot deformity can cause function disability.For most patients were diagnosed in early children,so function disability evaluation and effective treatment from children is significant to their prognosis.

  2. Hereditary hyperbilirubinemias

    Directory of Open Access Journals (Sweden)

    Radlović Nedeljko

    2014-01-01

    Full Text Available Inherited disorders of bilirubin metabolism involve four autosomal recessive syndromes: Gilbert, Crigler- Najjar, Dubin-Johnson and Rotor, among which the first two are characterized by unconjugated and the second two by conjugated hyperbilirubinemia. Gilbert syndrome occurs in 2%-10% of general population, while others are rare. Except for Crigler-Najjar syndrome, hereditary hyperbilirubinemias belong to benign disorders and thus no treatment is required.

  3. Increasing cutaneous afferent feedback improves proprioceptive accuracy at the knee in patients with sensory ataxia.

    Science.gov (United States)

    Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Goulding, Niamh; Palma, Jose-Alberto; Fuente Mora, Cristina; Kaufmann, Horacio

    2016-02-01

    Hereditary sensory and autonomic neuropathy type III (HSAN III) features disturbed proprioception and a marked ataxic gait. We recently showed that joint angle matching error at the knee is positively correlated with the degree of ataxia. Using intraneural microelectrodes, we also documented that these patients lack functional muscle spindle afferents but have preserved large-diameter cutaneous afferents, suggesting that patients with better proprioception may be relying more on proprioceptive cues provided by tactile afferents. We tested the hypothesis that enhancing cutaneous sensory feedback by stretching the skin at the knee joint using unidirectional elasticity tape could improve proprioceptive accuracy in patients with a congenital absence of functional muscle spindles. Passive joint angle matching at the knee was used to assess proprioceptive accuracy in 25 patients with HSAN III and 9 age-matched control subjects, with and without taping. Angles of the reference and indicator knees were recorded with digital inclinometers and the absolute error, gradient, and correlation coefficient between the two sides calculated. Patients with HSAN III performed poorly on the joint angle matching test [mean matching error 8.0 ± 0.8° (±SE); controls 3.0 ± 0.3°]. Following application of tape bilaterally to the knee in an X-shaped pattern, proprioceptive performance improved significantly in the patients (mean error 5.4 ± 0.7°) but not in the controls (3.0 ± 0.2°). Across patients, but not controls, significant increases in gradient and correlation coefficient were also apparent following taping. We conclude that taping improves proprioception at the knee in HSAN III, presumably via enhanced sensory feedback from the skin.

  4. Hereditary motor and sensory neuropathy with congenital glaucoma: report on a family Neuropatia hereditária sensitivo-motora com glaucoma congênito: descrição de uma família

    Directory of Open Access Journals (Sweden)

    WALTER O. ARRUDA

    1999-06-01

    Full Text Available We report three siblings of a family with hereditary motor and sensory polyneuropathy (HMSN and buphthalmos. Electrophysiological studies showed a demyelinating neuropathy and pathological findings showed severe loss of myelinated fibers (MF, thin myelin sheaths and myelin infoldings in a few remaining MF. The presumed mode of inheritance is autosomal recessive. This family probably represents an unique form of CMT4 that may be related to one of the congenital glaucoma genic locus, particularly GLC3A and GLC3B, described in Turkish families.Descrevemos três membros afetados de uma família com neuropatia hereditária sensitivo-motora tipo I (desmielinizante e glaucoma congênito (buftalmia. O estudo eletrofisiológico dos membros afetados demonstrou polineuropatia sensitivo-motora desmielinizante, com ausência ou redução acentuada das velocidades de neurocondução sensitiva e motora. A biópsia do nervo sural revelou redução moderada a grave das fibras mielinizadas, bainhas de mielina de espessura diminuída (remielinização com dobramentos delas nas poucas fibras mielinizadas remanescentes. Não foram observadas formações em casca de cebola, nem tampouco alterações hipertróficas. O padrão de herança desta família parece ser autossômico recessivo. Sugerimos tratar-se de uma forma singular de doença de Charcot-Marie-Tooth autossômica recessiva (CMT4, que eventualmente pode possuir locus gênico próximo a um dos locus do glaucoma congênito (GLC3A e GLC3B, localizados nos cromossomos 2p21 e 1p36.

  5. Hereditary spherocytosis

    Directory of Open Access Journals (Sweden)

    Meenakshi Kalyan

    2014-01-01

    Full Text Available Hereditary spherocytosis (HS is a familial hemolytic disorder with marked heterogeneity of clinical features, ranging from an asymptomatic condition to a fulminant hemolytic anemia. In severe cases, the disorder may present in early childhood, but in some cases it may go unnoticed until later in adult life. We present a 32-year-old male who presented with anemia, jaundice, splenomegaly, and gallstones. Seven of his family members had similar illness in the past. The Mother died of similar illness at the age of 40. The Blood film showed spherocytosis and reticulocytosis. There was increased osmotic fragility and a negative direct coomb′s test. He was given folic acid supplements and was advised for splenectomy and cholecystectomy. This case is reported due to its rarity in Indian population.

  6. [The role of the immune system in hereditary demyelinating neuropathies].

    Science.gov (United States)

    Mäurer, M; Toyka, K V; Martini, R

    2005-06-01

    Hereditary neuropathies, e.g., Charcot-Marie-Tooth (CMT) disease, are inherited diseases of the peripheral nervous system causing chronic progressive motor and sensory dysfunction. Most neuropathies are due to mutations in myelin genes such as PMP22, P0, and the gap junction protein Cx32. Myelin mutant mice are regarded as suitable animal models for several forms of hereditary neuropathies and are important neurobiological tools for the evaluation of pathogenetic and therapeutic concepts in hereditary neuropathies. Using these animal models we could recently show that the immune system is involved in the pathogenesis of hereditary neuropathies. Due to the phenotypic similarities we also consider the immune system important for human inherited neuropathies, in particular since several case reports demonstrate a beneficial effect of immune therapies in patients with hereditary neuropathies. In this review we compare findings from animal models and human disease to elucidate the role of the immune system in hereditary neuropathies.

  7. Hereditary neuropathies: systematization and diagnostics (clinical case of hereditary motor and sensor neuropathy of the IA type

    Directory of Open Access Journals (Sweden)

    Kolokolova A.M.

    2016-09-01

    Full Text Available Aim: to study the value of routine methods (clinical symptoms, electrophysiological findings and results of DNA analysis in diagnostics of hereditary motor sensory neuropathy type IA in outpatient clinics. Material and Methods. The review of foreign literature is represented. The phenotypic polymorphism, genetic heterogeneity and the difficulties of diagnostics are identified. A family with hereditary motor sensory neuropathy of lAtype is presented, which was diagnosed on the base of available methods in outpatient practice (clinical symptoms, genealogical method, electro-physiological findings and DNA analysis results. Results. Routine algorithm (consistent valuation of clinical symptoms, neurophysiologic findings and the results of DNA analysis helped to verify the diagnosis of hereditary motor sensory neuropathy of lAtype in outpatient practice after more than 20 years of the onset of the disease. Conclusion. The neurologists of outpatient clinics and other specialists must be informed about the availability of diagnostics of hereditary diseases of nervous system.

  8. [Diagnosis of hereditary angioedema].

    Science.gov (United States)

    Bouillet, Laurence

    2015-01-01

    Hereditary angioedema is a rare disease, potentially life-threatening. It requires a specific treatment. Angioedema without wheals associated with abdominal attacks are very specific of this disease. Antigenemy and functional C1Inhibitor assays are necessary for the diagnosis. The hereditary angioedema with normal C1Inh (type III) is a diagnostic challenge. Bradykinin, secondary to kallikrein-kinin system activation is the key mediator of hereditary angioedema. Female are more symptomatic. Attacks can be induced by menstruations, pregnancies or contraceptive pills.

  9. Genetics Home Reference: hereditary spherocytosis

    Science.gov (United States)

    ... Understand Genetics Home Health Conditions hereditary spherocytosis hereditary spherocytosis Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Hereditary spherocytosis is a condition that affects red blood cells. ...

  10. Hereditary urea cycle abnormality

    Science.gov (United States)

    ... vitro so the specific genetic cause is known. Teamwork between parents, the affected child, and doctors can help prevent severe illness. Alternative Names Abnormality of the urea cycle - hereditary; Urea cycle - hereditary abnormality Images Male urinary system Urea cycle References Lichter-Konecki ...

  11. Korean Version of the Scale for the Assessment and Rating of Ataxia in Ataxic Stroke Patients

    OpenAIRE

    Kim, Bo-Ram; Lee, Jin-Youn; Kim, Min Jeong; Jung, Heeyoune; Lee, Jongmin

    2014-01-01

    Objective To investigate the intra-rater and inter-rater reliability and usefulness of the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) in ataxic stroke patients. Methods The original SARA was translated into Korean, back translated to English, and compared to the original version. Stroke patients (n=60) with ataxia were evaluated using the K-SARA by one physiatrist and one occupational therapist. All subjects were rated twice. We divided the subjects into 5 gr...

  12. The Effects of Topic Knowledge on Intelligibility and Lexical Segmentation in Hypokinetic and Ataxic Dysarthria.

    Science.gov (United States)

    Utianski, Rene L; Lansford, Kaitlin L; Liss, Julie M; Azuma, Tamiko

    2011-12-01

    Benefits to speech intelligibility can be achieved by enhancing a listener's ability to decipher it. However, much remains to be learned about the variables that influence the effectiveness of various listener-based manipulations. This study examined the benefit of providing listeners with the topic of some phases produced by speakers with either hypokinetic or ataxic dysarthria. Total and topic word accuracy, topic-related substitutions, and lexical boundary errors were calculated from the listener transcripts. Data were compared with those who underwent a familiarization process (reported by Liss, Spitzer, Caviness, & Adler, 2002) and with those inexperienced with disordered speech (reported by Liss Spitzer, Caviness, & Adler, 2000). Results revealed that listeners of ataxic speech provided with topic knowledge obtained higher intelligibility scores than naïve listeners. The magnitude of benefit was similar to the familiarization condition. However, topic word and word substitution analyses revealed different underlying perceptual mechanisms responsible for the observed benefit. No differences attributable to listening condition were discovered in lexical segmentation patterns. Overall, the results support the need for further study of listener-based manipulations to elucidate the mechanisms responsible for the observed perceptual benefits for each dysarthria type.

  13. De novo point mutations in patients diagnosed with ataxic cerebral palsy.

    Science.gov (United States)

    Parolin Schnekenberg, Ricardo; Perkins, Emma M; Miller, Jack W; Davies, Wayne I L; D'Adamo, Maria Cristina; Pessia, Mauro; Fawcett, Katherine A; Sims, David; Gillard, Elodie; Hudspith, Karl; Skehel, Paul; Williams, Jonathan; O'Regan, Mary; Jayawant, Sandeep; Jefferson, Rosalind; Hughes, Sarah; Lustenberger, Andrea; Ragoussis, Jiannis; Jackson, Mandy; Tucker, Stephen J; Németh, Andrea H

    2015-07-01

    Cerebral palsy is a sporadic disorder with multiple likely aetiologies, but frequently considered to be caused by birth asphyxia. Genetic investigations are rarely performed in patients with cerebral palsy and there is little proven evidence of genetic causes. As part of a large project investigating children with ataxia, we identified four patients in our cohort with a diagnosis of ataxic cerebral palsy. They were investigated using either targeted next generation sequencing or trio-based exome sequencing and were found to have mutations in three different genes, KCNC3, ITPR1 and SPTBN2. All the mutations were de novo and associated with increased paternal age. The mutations were shown to be pathogenic using a combination of bioinformatics analysis and in vitro model systems. This work is the first to report that the ataxic subtype of cerebral palsy can be caused by de novo dominant point mutations, which explains the sporadic nature of these cases. We conclude that at least some subtypes of cerebral palsy may be caused by de novo genetic mutations and patients with a clinical diagnosis of cerebral palsy should be genetically investigated before causation is ascribed to perinatal asphyxia or other aetiologies. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

  14. The effects of familiarization on intelligibility and lexical segmentation in hypokinetic and ataxic dysarthria

    Science.gov (United States)

    Liss, Julie M.; Spitzer, Stephanie M.; Caviness, John N.; Adler, Charles

    2002-12-01

    This study is the third in a series that has explored the source of intelligibility decrement in dysarthria by jointly considering signal characteristics and the cognitive-perceptual processes employed by listeners. A paradigm of lexical boundary error analysis was used to examine this interface by manipulating listener constraints with a brief familiarization procedure. If familiarization allows listeners to extract relevant segmental and suprasegmental information from dysarthric speech, they should obtain higher intelligibility scores than nonfamiliarized listeners, and their lexical boundary error patterns should approximate those obtained in misperceptions of normal speech. Listeners transcribed phrases produced by speakers with either hypokinetic or ataxic dysarthria after being familiarized with other phrases produced by these speakers. Data were compared to those of nonfamiliarized listeners [Liss et al., J. Acoust. Soc. Am. 107, 3415-3424 (2000)]. The familiarized groups obtained higher intelligibility scores than nonfamiliarized groups, and the effects were greater when the dysarthria type of the familiarization procedure matched the dysarthria type of the transcription task. Remarkably, no differences in lexical boundary error patterns were discovered between the familiarized and nonfamiliarized groups. Transcribers of the ataxic speech appeared to have difficulty distinguishing strong and weak syllables in spite of the familiarization. Results suggest that intelligibility decrements arise from the perceptual challenges posed by the degraded segmental and suprasegmental aspects of the signal, but that this type of familiarization process may differentially facilitate mapping segmental information onto existing phonological categories.

  15. [Hereditary optic neuropathies].

    Science.gov (United States)

    Milea, D; Verny, C

    2012-10-01

    Hereditary optic neuropathies are a group of heterogeneous conditions affecting both optic nerves, with an autosomal dominant, autosomal recessive, X-related or mitochondrial transmission. The two most common non-syndromic hereditary optic neuropathies (Leber's hereditary optic neuropathy and autosomal dominant optic atrophy) are very different in their clinical presentation and their genetic transmission, leading however to a common, non-specific optic nerve atrophy. Beyond the optic atrophy-related visual loss, which is the clinical hallmark of this group of diseases, other associated neurological signs are increasingly recognized.

  16. Is Pancreatic Cancer Hereditary?

    Science.gov (United States)

    ... gene testing for hereditary pancreatitis is now available. Ataxia telangiectasia The team at Johns Hopkins discovered that inherited ... are known to cause the clinical syndrome of "ataxia telangiectasia," and 2-3% of people with familial pancreatic ...

  17. Hereditary Gingival Fibromatosis

    Science.gov (United States)

    Nevin, N. C.

    1971-01-01

    Case studies of two siblings suffering from a gum disorder in which enlargement of the gingival mucosa is caused by a fibrosis. The disorder in the two children was felt to be an hereditary recessive trait. (CD)

  18. Learning about Hereditary Hemochromatosis

    Science.gov (United States)

    ... and Its Implications Meeting A 1997 ELSI Report Learning About Hereditary Hemochromatosis What do we know about ... and treatment information. Hosted by the Dolan DNA Learning Center at Cold Spring Harbor Laboratory. Iron Overload ...

  19. Combination Treatment of Low-Frequency Repetitive Transcranial Magnetic Stimulation and Intensive Occupational Therapy for Ataxic Hemiparesis due to Thalamic Hemorrhage

    Directory of Open Access Journals (Sweden)

    Naoki Urushidani

    2017-07-01

    Full Text Available Background: Both low-frequency repetitive transcranial magnetic stimulation (LF-rTMS and intensive occupational therapy (OT are clinically beneficial for post-stroke patients with upper-limb hemiparesis. However, the usefulness of LF-rTMS and intensive OT for ataxic hemiparesis (AH is unknown. Methods: The study subjects included 7 patients with AH. All patients had ataxia and mild hemiparesis without a sensory disturbance that was due to thalamic hemorrhage. Each patient was scheduled to receive 20-min rTMS at 1 Hz at the contralesional cerebral hemisphere followed by 120-min intensive OT, daily for 21 sessions. The primary outcome was the motor function of the affected upper limb that was evaluated by using the Fugl-Meyer Assessment (FMA. In addition, the International Cooperative Ataxia Rating Scale (ICARS score was determined to assess the severity of ataxia. Results: All patients completed the protocol without any adverse effects. The FMA score significantly increased after treatment. Notably, the ICARS score also significantly decreased. Conclusions: Our proposed combination treatment is a safe and feasible neurorehabilitative intervention for patients with AH due to thalamic hemorrhage. Our results demonstrate the possibility that rTMS in combination with intensive OT could improve motor function and alleviated ataxia in patients with AH.

  20. Speech serial control in healthy speakers and speakers with hypokinetic or ataxic dysarthria: effects of sequence length and practice.

    Science.gov (United States)

    Reilly, Kevin J; Spencer, Kristie A

    2013-01-01

    The current study investigated the processes responsible for selection of sounds and syllables during production of speech sequences in 10 adults with hypokinetic dysarthria from Parkinson's disease, five adults with ataxic dysarthria, and 14 healthy control speakers. Speech production data from a choice reaction time task were analyzed to evaluate the effects of sequence length and practice on speech sound sequencing. Speakers produced sequences that were between one and five syllables in length over five experimental runs of 60 trials each. In contrast to the healthy speakers, speakers with hypokinetic dysarthria demonstrated exaggerated sequence length effects for both inter-syllable intervals (ISIs) and speech error rates. Conversely, speakers with ataxic dysarthria failed to demonstrate a sequence length effect on ISIs and were also the only group that did not exhibit practice-related changes in ISIs and speech error rates over the five experimental runs. The exaggerated sequence length effects in the hypokinetic speakers with Parkinson's disease are consistent with an impairment of action selection during speech sequence production. The absent length effects observed in the speakers with ataxic dysarthria is consistent with previous findings that indicate a limited capacity to buffer speech sequences in advance of their execution. In addition, the lack of practice effects in these speakers suggests that learning-related improvements in the production rate and accuracy of speech sequences involves processing by structures of the cerebellum. Together, the current findings inform models of serial control for speech in healthy speakers and support the notion that sequencing deficits contribute to speech symptoms in speakers with hypokinetic or ataxic dysarthria. In addition, these findings indicate that speech sequencing is differentially impaired in hypokinetic and ataxic dysarthria.

  1. Speech serial control in healthy speakers and speakers with hypokinetic or ataxic dysarthria: Effects of sequence length and practice

    Directory of Open Access Journals (Sweden)

    Kevin J Reilly

    2013-10-01

    Full Text Available The current study investigated the processes responsible for selection of sounds and syllables during production of speech sequences in 10 adults with hypokinetic dysarthria from Parkinson’s disease, 5 adults with ataxic dysarthria, and 14 healthy control speakers. Speech production data from a choice reaction time task were analyzed to evaluate the effects of sequence length and practice on speech sound sequencing. Speakers produced sequences that were between one and five syllables in length over five experimental runs of 60 trials each. In contrast to the healthy speakers, speakers with hypokinetic dysarthria demonstrated exaggerated sequence length effects for both inter-syllable intervals (ISIs and speech error rates. Conversely, speakers with ataxic dysarthria failed to demonstrate a sequence length effect on ISIs and were also the only group that did not exhibit practice-related changes in ISIs and speech error rates over the five experimental runs. The exaggerated sequence length effects in the hypokinetic speakers with Parkinson’s disease are consistent with an impairment of action selection during speech sequence production. The absent length effects observed in the speakers with ataxic dysarthria is consistent with previous findings that indicate a limited capacity to buffer speech sequences in advance of their execution. In addition, the lack of practice effects in these speakers suggests that learning-related improvements in the production rate and accuracy of speech sequences involves processing by structures of the cerebellum. Together, the current findings inform models of serial control for speech in healthy speakers and support the notion that sequencing deficits contribute to speech symptoms in speakers with hypokinetic or ataxic dysarthria. In addition, these findings indicate that speech sequencing is differentially impaired in hypokinetic and ataxic dysarthria.

  2. The distal hereditary motor neuropathies.

    Science.gov (United States)

    Rossor, Alexander M; Kalmar, Bernadett; Greensmith, Linda; Reilly, Mary M

    2012-01-01

    The distal hereditary motor neuropathies (dHMN) comprise a heterogeneous group of diseases that share the common feature of a length-dependent predominantly motor neuropathy. Many forms of dHMN have minor sensory abnormalities and/or a significant upper-motor-neuron component, and there is often an overlap with the axonal forms of Charcot-Marie-Tooth disease (CMT2) and with juvenile forms of amyotrophic lateral sclerosis and hereditary spastic paraplegia. Eleven causative genes and four loci have been identified with autosomal dominant, recessive and X-linked patterns of inheritance. Despite advances in the identification of novel gene mutations, 80% of patients with dHMN have a mutation in an as-yet undiscovered gene. The causative genes have implicated proteins with diverse functions such as protein misfolding (HSPB1, HSPB8, BSCL2), RNA metabolism (IGHMBP2, SETX, GARS), axonal transport (HSPB1, DYNC1H1, DCTN1) and cation-channel dysfunction (ATP7A and TRPV4) in motor-nerve disease. This review will summarise the clinical features of the different subtypes of dHMN to help focus genetic testing for the practising clinician. It will also review the neuroscience that underpins our current understanding of how these mutations lead to a motor-specific neuropathy and highlight potential therapeutic strategies. An understanding of the functional consequences of gene mutations will become increasingly important with the advent of next-generation sequencing and the need to determine the pathogenicity of large amounts of individual genetic data.

  3. Sensory neuropathies, from symptoms to treatment.

    Science.gov (United States)

    Botez, Stephan A; Herrmann, David N

    2010-10-01

    The present review focuses on recent developments in diagnosis and treatment of sensory neuropathies. It does not seek to establish a comprehensive classification of sensory neuropathies, nor treatment guidelines per se. Diagnostic criteria and guidelines have been developed for distal symmetric polyneuropathies, small fiber sensory neuropathies and sensory neuronopathies. Novel diagnostic tools such as skin biopsies now allow diagnosis of small fiber sensory neuropathies. Genetic testing has defined new subtypes of mitochondrial neuropathies and inherited neuropathies with sensory involvement. Intravenous immunoglobulin and tumor necrosis factor-alpha inhibitors show promise for some dysimmune sensory neuropathies or neuronopathies. Additional options for management of neuropathic pain are emerging. Diagnostic methods for both acquired and hereditary sensory neuropathies have progressed in recent years, leading to earlier and more specific diagnoses and a better understanding of disease mechanisms. Much progress remains to be made regarding symptomatic and disease-modifying therapy for a range of sensory neuropathies, including those due to diabetes, HIV infection and from dysimmune or hereditary causes.

  4. Genetics Home Reference: hereditary angioedema

    Science.gov (United States)

    ... InfoSearch: Hereditary angioedema MalaCards: c1 inhibitor deficiency Merck Manual Professional Version Orphanet: Hereditary angioedema Patient Support and Advocacy Resources (2 links) International Patient Organization for C1 Inhibitor Deficiencies National Organization for Rare ...

  5. Hereditary periodic fever syndromes

    NARCIS (Netherlands)

    McDermott, MF; Frenkel, J

    Hereditary periodic fever syndromes are defined by recurrent attacks of generalised inflammation for which no infectious or auto-immune cause can be identified. For most of these disorders, the molecular basis has recently been elucidated. This has opened the prospect of novel therapeutic

  6. Managing hereditary ovarian cancer

    NARCIS (Netherlands)

    Mourits, M. J.; de Bock, G. H.

    2009-01-01

    In this review we present an overview of recent developments in the management of hereditary ovarian cancer. Until recently, intensive screening of the ovaries was recommended to mutation carriers and their first-degree female relatives. However, since screening is not effective in detecting early-s

  7. Understanding Hereditary Angioedema

    Science.gov (United States)

    ... INH) in their blood or this C1-INH protein does not function appropriately. These forms of hereditary angioedema are different ... In addition to a physical examination and medical history, HAE is diagnosed by measuring the level and function of C1-INH in the blood. Living with ...

  8. Hereditary Angioedema in Childhood

    DEFF Research Database (Denmark)

    Kjaer, Line; Bygum, Anette

    2012-01-01

    Hereditary angioedema (HAE) is a rare inherited disease that is often difficult to diagnose. We report a case of a 9-year-old boy with a spontaneous mutation causing HAE, diagnosed after a life-threatening episode of angioedema of the head and upper respiratory tract after a 5-year history...

  9. Hereditary Hearing Loss.

    Science.gov (United States)

    Tran, LenhAnh P.; Grundfast, Kenneth M.

    1997-01-01

    This article discusses inheritance patterns in hearing loss, epidemiology, clues to genetic causes, locating genes that cause hereditary disorders, genes related to hearing loss disorders in individuals with Usher syndrome, Waardenburg syndrome, Treacher-Collins syndrome, Branchio-oto-renal and Pendred syndromes, and the significance of finding…

  10. The effect of prior alcohol consumption on the ataxic response to alcohol in high-alcohol preferring mice.

    Science.gov (United States)

    Fritz, Brandon M; Boehm, Stephen L

    2014-12-01

    We have previously shown that ethanol-naïve high-alcohol preferring (HAP) mice, genetically predisposed to consume large quantities of alcohol, exhibited heightened sensitivity and more rapid acute functional tolerance (AFT) to alcohol-induced ataxia compared to low-alcohol preferring mice. The goal of the present study was to evaluate the effect of prior alcohol self-administration on these responses in HAP mice. Naïve male and female adult HAP mice from the second replicate of selection (HAP2) underwent 18 days of 24-h, 2-bottle choice drinking for 10% ethanol vs. water, or water only. After 18 days of fluid access, mice were tested for ataxic sensitivity and rapid AFT following a 1.75 g/kg injection of ethanol on a static dowel apparatus in Experiment 1. In Experiment 2, a separate group of mice was tested for more protracted AFT development using a dual-injection approach where a second, larger (2.0 g/kg) injection of ethanol was given following the initial recovery of performance on the task. HAP2 mice that had prior access to alcohol exhibited a blunted ataxic response to the acute alcohol challenge, but this pre-exposure did not alter rapid within-session AFT capacity in Experiment 1 or more protracted AFT capacity in Experiment 2. These findings suggest that the typically observed increase in alcohol consumption in these mice may be influenced by ataxic functional tolerance development, but is not mediated by a greater capacity for ethanol exposure to positively influence within-session ataxic tolerance.

  11. Sequence complexity effects on speech production in healthy speakers and speakers with hypokinetic or ataxic dysarthria.

    Science.gov (United States)

    Reilly, Kevin J; Spencer, Kristie A

    2013-01-01

    The present study investigated the effects of sequence complexity, defined in terms of phonemic similarity and phonotoactic probability, on the timing and accuracy of serial ordering for speech production in healthy speakers and speakers with either hypokinetic or ataxic dysarthria. Sequences were comprised of strings of consonant-vowel (CV) syllables with each syllable containing the same vowel, /a/, paired with a different consonant. High complexity sequences contained phonemically similar consonants, and sounds and syllables that had low phonotactic probabilities; low complexity sequences contained phonemically dissimilar consonants and high probability sounds and syllables. Sequence complexity effects were evaluated by analyzing speech error rates and within-syllable vowel and pause durations. This analysis revealed that speech error rates were significantly higher and speech duration measures were significantly longer during production of high complexity sequences than during production of low complexity sequences. Although speakers with dysarthria produced longer overall speech durations than healthy speakers, the effects of sequence complexity on error rates and speech durations were comparable across all groups. These findings indicate that the duration and accuracy of processes for selecting items in a speech sequence is influenced by their phonemic similarity and/or phonotactic probability. Moreover, this robust complexity effect is present even in speakers with damage to subcortical circuits involved in serial control for speech.

  12. Sequence complexity effects on speech production in healthy speakers and speakers with hypokinetic or ataxic dysarthria.

    Directory of Open Access Journals (Sweden)

    Kevin J Reilly

    Full Text Available The present study investigated the effects of sequence complexity, defined in terms of phonemic similarity and phonotoactic probability, on the timing and accuracy of serial ordering for speech production in healthy speakers and speakers with either hypokinetic or ataxic dysarthria. Sequences were comprised of strings of consonant-vowel (CV syllables with each syllable containing the same vowel, /a/, paired with a different consonant. High complexity sequences contained phonemically similar consonants, and sounds and syllables that had low phonotactic probabilities; low complexity sequences contained phonemically dissimilar consonants and high probability sounds and syllables. Sequence complexity effects were evaluated by analyzing speech error rates and within-syllable vowel and pause durations. This analysis revealed that speech error rates were significantly higher and speech duration measures were significantly longer during production of high complexity sequences than during production of low complexity sequences. Although speakers with dysarthria produced longer overall speech durations than healthy speakers, the effects of sequence complexity on error rates and speech durations were comparable across all groups. These findings indicate that the duration and accuracy of processes for selecting items in a speech sequence is influenced by their phonemic similarity and/or phonotactic probability. Moreover, this robust complexity effect is present even in speakers with damage to subcortical circuits involved in serial control for speech.

  13. New ataxic tottering-6j mouse allele containing a Cacna1a gene mutation.

    Directory of Open Access Journals (Sweden)

    Weidong Li

    Full Text Available Voltage-gated Ca(2+ (Ca(v channels control neuronal functions including neurotransmitter release and gene expression. The Cacna1a gene encodes the α1 subunit of the pore-forming Ca(v2.1 channel. Mice with mutations in this gene form useful tools for defining channel functions. The recessive ataxic tottering-6j strain that was generated in the Neuroscience Mutagenesis Facility at The Jackson Laboratory has a mutation in the Cacna1a gene. However, the effect of this mutation has not been investigated in detail. In this study, mutation analysis shows a base substitution (C-to-A in the consensus splice acceptor sequence linked to exon 5, which results in the skipping of exon 5 and the splicing of exon 4 directly to exon 6. The effect of this mutation is expected to be severe as the expressed α1 subunit protein lacks a significant part of the S4-S5 linker, S5, and part of S5-S6 linker in domain I. Tottering-6j mice display motor dysfunctions in the footprint, rotating rod, and hind-limb extension tests. Although cytoarchitecture of the mutant brains appears normal, tyrosine hydroxylase was persistently expressed in cerebellar Purkinje cells in the adult mutant mice. These results indicate that tottering-6j is a useful model for functional studies of the Ca(v2.1 channel.

  14. Human hereditary hepatic porphyrias.

    Science.gov (United States)

    Nordmann, Yves; Puy, Hervé

    2002-11-01

    The human hereditary hepatic porphyrias are diseases due to marked deficiencies of enzymes in the heme biosynthetic pathway. Porphyrias can be classified as either hepatic or erythroid, depending on the major production site of porphyrins or their precursors. The pathogenesis of inherited hepatic porphyrias has now been defined at the molecular level. Some gene carriers are vulnerable to a range of exogenous and endogenous factors, which may trigger neuropsychiatric and/or cutaneous symptoms. Early diagnosis is of prime importance since it makes way for counselling. In this article we present an overview of recent advances on hepatic porphyrias: 5-aminolevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria (AIP), porphyria cutanea tarda (PCT), hereditary coproporphyria (HC), and variegate porphyria (VP).

  15. Hereditary breast cancer

    DEFF Research Database (Denmark)

    Larsen, Martin J; Thomassen, Mads; Gerdes, Anne-Marie

    2014-01-01

    Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight into the t......Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight...... into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing...... on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well...

  16. Hereditary erythrocytosis, thrombocytosis and neutrophilia.

    Science.gov (United States)

    Hong, Wan-Jen; Gotlib, Jason

    2014-06-01

    Hereditary erythrocytosis, thrombocytosis, and neutrophilia are rare inherited syndromes which exhibit Mendelian inheritance. Some patients with primary hereditary erythrocytosis exhibit a mutation in the erythropoietin receptor (EPOR) which is associated with low serum erythropoietin (EPO) levels. Secondary congenital erythrocytosis may be characterized by normal or high serum EPO levels, and is related to high oxygen affinity haemoglobin variants, mutation of the enzyme biphosphoglycerate mutase (BPGM), or defects in components of the oxygen-sensing pathway. Hereditary thrombocytosis was first linked to mutations in genes encoding thrombopoietin (THPO) or the thrombopoietin receptor, MPL. More recently, germline mutations in JAK2, distinct from JAK2 V617F, and mutation of the gelsolin gene, were uncovered in several pedigrees of hereditary thrombocytosis. Hereditary neutrophilia has been described in one family with an activating germline mutation in CSF3R. The mutational basis for most hereditary myeloproliferative disorders has yet to be identified. Copyright © 2014. Published by Elsevier Ltd.

  17. Genetics Home Reference: hereditary diffuse gastric cancer

    Science.gov (United States)

    ... Health Conditions hereditary diffuse gastric cancer hereditary diffuse gastric cancer Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Hereditary diffuse gastric cancer (HDGC) is an inherited disorder that greatly increases ...

  18. 线粒体融合蛋白2基因新突变导致的遗传性运动感觉性神经病6型一家系%A new MFN2 gene mutation resulting in hereditary motor and sensory neuropathy type 6, a family report

    Institute of Scientific and Technical Information of China (English)

    吕鹤; 洪道俊; 李务荣; 王朝霞; 袁云

    2011-01-01

    目的 报道1个遗传性运动感觉性神经病6型家系的临床表现、病理改变以及基因突变特点。方法 先证者男性,15岁。患者5岁出现双下肢无力,症状进行性加重,伴随出现双足跟腱挛缩;11岁开始出现慢性进行性视力下降;12岁出现双手肌肉萎缩,无肢体麻木。周围神经传导速度检查显示诱发电位未能引出或波幅显著下降,感觉神经较运动神经改变更明显。视诱发电位提示双眼P100潜伏期均延长,波幅正常。眼底照相提示视神经萎缩,视网膜电图正常。患者母亲7岁时开始出现走路费力,10岁出现视力下降。对先证者进行腓肠神经活体组织检查。对先证者及其母亲进行线粒体融合蛋白2( MFN2)基因测序,100名健康人作为正常对照。结果 腓肠神经病理改变主要为有髓神经纤维显著减少,电镜检查发现个别有髓神经纤维出现洋葱球样结构和再生簇结构,个别神经纤维的轴索内可见线粒体聚集和空泡化。先证者和母亲的MFN2基因第19号外显子存在c.2218T>C杂合突变,导致MFN2第740位的色氨酸由精氨酸替代(W740R)。100名健康对照没有发现该突变。结论 MFN2基因c.2218T>C突变导致了遗传性运动感觉性神经病6型,其视力下降多出现在脊神经损害之后,周围神经可以存在髓鞘损害。%Objective To report clinical, pathological and molecular genetic features in a Chinese family with hereditary motor and sensory neuropathy type 6. Methods The index case is a 15 years old boy. He developed progressive distal limb weakness at the age of 5. The disease deteriorated slowly,accompanied with contracture of achilles' tendon. At the age of 11 years old he suffered from decrease of visual acuity. At the age of 12, he found the muscular atrophy of both hands without sensory disturbances.Visual evoked potential revealed prolonged latency of bilateral P100. Ophthalmological

  19. Hereditary angioedema in women

    Directory of Open Access Journals (Sweden)

    Bouillet Laurence

    2010-07-01

    Full Text Available Abstract Women with hereditary angioedema (HAE are more likely to be symptomatic that men. Hormonal factors (puberty, contraception, pregnancy,.... play a significant role in the precipitation or worsening of the condition in women. So, combined contraceptive pills are not indicated and progestogen pill must be preferred. During pregnancy, attack rate can increase (38-48% of women. C1Inhibitor concentrate and tranexamic acid can be used during pregnancy. Attenuated androgens for long term prophylaxis are effective but side effects appear more often in female patients. These side effects are dose dependant and can be attenuated by titrating the dose down the lowest effective level.

  20. HFE-associated hereditary hemochromatosis

    NARCIS (Netherlands)

    Eijkelkamp, EJ; Yapp, TR; Powell, LW

    2000-01-01

    Hereditary hemochromatosis is a common inherited disorder of the iron metabolism Screening studies indicate that it has a prevalence of one in 200 to 400, depending on the population studied, and a carrier rate of about one in seven to one in 10. Feder et al identified the hereditary hemochromatosis

  1. Molecular genetics of distal hereditary motor neuropathies.

    Science.gov (United States)

    Irobi, Joy; De Jonghe, Peter; Timmerman, Vincent

    2004-10-01

    Inherited peripheral neuropathies comprise a wide variety of diseases primarily affecting the peripheral nervous system. The best-known peripheral neuropathy is Charcot-Marie-Tooth disease (CMT) described in 1886 by J.-M. Charcot, P. Marie and H.H. Tooth. In 1980, A.E. Harding and P.K. Thomas showed that in a large group of individuals with CMT, several only had motor abnormalities on clinical and electrophysiological examination, whereas sensory abnormalities were absent. This exclusively motor variant of CMT was designated as spinal CMT or hereditary distal spinal muscular atrophy, and included in the distal hereditary motor neuropathies (distal HMN). The distal HMN are clinically and genetically heterogeneous and are subdivided according to the mode of inheritance, age at onset and clinical evolution. Since the introduction of positional cloning, 12 chromosomal loci and seven disease-causing genes have been identified for autosomal dominant and recessive distal HMN. Most of the genes involved have housekeeping functions, as in RNA processing, translation synthesis, glycosylation, stress response, apoptosis, but also axonal trafficking and editing. Functional characterization of the mutations will help to unravel the cellular processes that underlie the specificity of motor neuropathies leading to neurogenic muscular atrophy of distal limb muscles. Here we review the recent progress of the molecular genetics of distal HMN and discuss the genes implicated.

  2. CONGENITAL SENSORY NEUROPATHY (HSAN II

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    Venkata Chalam

    2015-08-01

    Full Text Available A 5 year old girl having hereditary sensory neuropathy, type II manifesting as congenital absence of pain sensation and trophic changes in the skin is reported. This child presented with presented with multiple ulcers over hands and feet since 2 years of age. The ulcers were non - healing type with serosanguineous discharge. There is abnormal gait and weakness in upper and lower limbs. On examination there are deep ulcers measuring 5x7x2cms over left feet. Fingers of both hands and feet were mutilated with loss of phalanges, sensations to fine touch, pain and temperature are decreased bilaterally below the mid arm and feet, vibration sensations were normal, proprioception could not be tested due to deformities. Sensory and motor nerve conduction studies showed evidence of sensorimotor axonal neuropathy.

  3. 儿童遗传性周围神经病%Hereditary Peripheral Neuropathy in Children

    Institute of Scientific and Technical Information of China (English)

    吕俊兰

    2006-01-01

    早在1886年Chareot、Marie和Tooth就报道了腓骨肌萎缩症(peroneal muscular atrophy),但直到1956年,由于神经电生理和腓肠神经活检的广泛开展和应用,才使周围神经病的分类成为可能。1984年Dyck将遗传性周围神经病分为遗传性运动神经病(hereditary motor neuropathy,HMN),遗传性感觉自主神经病(hereditary sensory and autonomic neuropathy,HSAN)以及遗传性运动和感觉神经病(hereditary motor and sensory neuropathy,HMSN)。

  4. Hereditary angioedema: Not an allergy

    Directory of Open Access Journals (Sweden)

    Sanjay Bhivgade

    2012-01-01

    Full Text Available Hereditary angioedema is a genetic disorder due to a deficiency or malfunction of C1 esterase inhibitor. We herein describe a case of 25-year-old male who presented with swelling over face since one day. There was history of similar episodes since two years with gradual subsidence of swelling without any treatment. Investigations revealed grossly reduced complement C4 and C1 esterase inhibitor level. Patient was diagnosed to have hereditary angioedema type 1 and started on stanozolol 2 mg three times a day with no recurrence in one year of follow-up. Hereditary angioedema resembles angioedema of an allergic reaction. However, the cause is different.

  5. A case report of congenital sensory neuropathy with anhidrosis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won Hyong; Chang, Hae Soon; Han, Man Chung; Lee, Suck Hyun; Lee, Duk Yong [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1974-10-15

    Congenital sensory neuropathy with anhidrosis is rare disease and may be confused with other cause of pain insensitivity or indifference. Other cause of pain insensitivity include congenital indifference to pain, congenital sensory neuropathy, hereditary sensory radicular neuropathy, nonprogressive sensory radicular neuropathy, syringomyelia, and hysterical analgesia. It is hereditary disease which is transmitted with autosomal recessive trait. The patient is 8 years old Korean male with complaint of swelling and local heat on right knee joint. Generalized analgesia is noted on physical examination. The skin is dry and coarse with no evidence of sweating. Delayed motor development was noted on early children. Mental development is retarded. On past history, patient showed unpredictable rises of temperature, though the general condition remained good. Multiple painless fracture on right humerus and right metatasal bone was occurred. Rt.knee radiograms show marked swelling of soft tissue and periosteal calcification on distal femru,which are resemble with neurotrophic joint.

  6. Hereditary colorectal cancer diagnostics

    DEFF Research Database (Denmark)

    Klarskov, Louise; Holck, Susanne; Bernstein, Inge

    2012-01-01

    BackgroundThe hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease......-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid...... in the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.Objective and methodsTo perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated with FCCTX...

  7. [Leber's hereditary optic neuropathy].

    Science.gov (United States)

    Leo-Kottler, B; Wissinger, B

    2011-12-01

    Leber's hereditary optic neuropathy (LHON) is a rare disease primarily affecting the retinal ganglion cells. In most cases patients with LHON develop permanent visual loss with a large central scotoma in the visual field of both eyes. The optic disc becomes partially or completely pale. At the onset of the disease many patients are considered to suffer from an optic neuritis and are treated under the diagnostic and therapeutic regimen of optic neuritis. LHON is mostly only considered when high dose cortisone therapy fails to be effective or the second eye is affected. Thereafter, molecular genetic analysis will prove LHON in these cases. Detailed anamnesis including pedigree analysis in combination with observance of the peripapillary microangiopathic alterations at the fundus will help to speed up the diagnosis of LHON, but even after exact clinical and molecular genetic diagnosis of LHON some aspects of the disease still remain a mystery today.

  8. Hereditary neuromuscular diseases

    Energy Technology Data Exchange (ETDEWEB)

    Oezsarlak, O. E-mail: ozkan.ozsarlak@uza.be; Schepens, E.; Parizel, P.M.; Goethem, J.W. van; Vanhoenacker, F.; Schepper, A.M. de; Martin, J.J

    2001-12-01

    This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible.

  9. Hereditary Elliptocytosis with Pyropoikilocytosis

    Directory of Open Access Journals (Sweden)

    Turan Bayhan

    2016-03-01

    Full Text Available A 17-day-old boy was admitted because of jaundice and anemia. He was born weighing 2900 g subsequent to a term gestation as the fourth child of first-degree cousin parents. The previous history revealed the administration of phototherapy for 4 days starting from the first day of life. Complete blood count revealed hemoglobin (Hb of 6.9 g/dL, hematocrit of 19.8%, mean corpuscular volume (MCV of 87.5 fL, red cell distribution width (RDW of 37%, white blood cell count of 11.4x109/L, and platelet count of 263x109/L. Corrected reticulocyte count was 5.3%. Peripheral blood smear revealed polychromasia and pyropoikilocytosis. Direct antibody test was negative. Erythrocyte glucose-6-phosphate dehydrogenase, pyruvate kinase, and pyrimidine 5’ nucleotidase levels were normal. An erythrocyte transfusion was administered with a diagnosis of non-immune hemolytic anemia and the patient was discharged at the 26th day of life with initiation of folic acid. During his outpatient followup, he required erythrocyte transfusions 2 more times and the last transfusion was performed when he was 3 months old. At a visit 3 months after the last transfusion, his blood count was as follows: Hb of 9.5 g/dL, hematocrit of 28.2%, MCV of 68.2 fL, and RDW of 30.5%. Erythrocyte osmotic fragility was found to be normal and Hb electrophoresis revealed Hb F of 6.6% and Hb A2 of 1.7%. Upon physical examination he had mild jaundice and no splenomegaly. The parents’ blood counts were within normal ranges. Peripheral blood smear revealed prominent elliptocytes and occasional microcytic and fragmented erythrocytes with poikilocytosis (Figure 1. The clinical findings and laboratory results were diagnostic for the hereditary pyropoikilocytosis (HPP type of hereditary elliptocytosis (HE, but in vitro fragmentation testing was not performed

  10. Hereditary peripheral neuropathies of childhood: an overview for clinicians.

    Science.gov (United States)

    Wilmshurst, Jo M; Ouvrier, Robert

    2011-11-01

    This review focuses on the "pure" hereditary peripheral neuropathies where peripheral nerve disease is the main manifestation and does not address neurodegenerative disorders associated with but not dominated by peripheral neuropathy. Aetiologies of childhood-onset peripheral neuropathies differ from those of adult-onset, with more inherited conditions, especially autosomal recessive. Charcot-Marie-Tooth disease is the commonest neuromuscular disorder. The genetic labels of CMT (Charcot-Marie-Tooth) disease types 1-4 are the preferred sub-type terms. Clinical presentations and molecular genetic heterogeneity of hereditary peripheral neuropathies are diverse. For most patients worldwide, diagnostic studies are limited to clinical assessment. Such markers which could be used to identify specific sub-types include presentation in early childhood, scoliosis, marked sensory involvement, respiratory compromise, upper limb involvement, visual or hearing impairment, pyramidal signs and mental retardation. These key markers may assist targeted genetic testing and aid in diagnosing children where DNA testing is not possible.

  11. Genetics Home Reference: hereditary sensory and autonomic neuropathy type II

    Science.gov (United States)

    ... unintentionally, typically by biting the tongue, lips, or fingers. These injuries may lead to loss of the affected areas, such as the tip of the tongue. Affected individuals often have injuries and fractures in their hands, feet, limbs, and joints that go untreated because ...

  12. [Hereditary phaeochromocytoma in twins].

    Science.gov (United States)

    Tóth, Géza; Patócs, Attila; Tóth, Miklós

    2016-08-01

    Phaeochromocytoma is a tumor of the catecholamine-producing cells of the adrenal gland. Extraadrenal phaeochromocytomas are frequently called paragangliomas. The majority of phaeochromocytomas are sporadic, however, about 25-30% are caused by genetic mutation. These tumor are frequently referred as hereditary phaeochromocytomas/paragangliomas. Their incidence increases continuously which can be attributed to availability of genetic examination and to the discovery of novel genes. The 47-year-old female patient underwent abdominal computed tomography which revealed bilateral adrenal gland enlargement. Abdominal magnetic resonance imaging, the 131-I- metaiodobenzylguanidine scintigraphy, urinary catecholamines and serum chomogranin A measurements confirmed the diagnosis of bilateral phaeochromocytomas. The genetically identical twin sister of the patient was also diagnosed with hormonally active bilateral phaechromocytoma, suggesting the genetic origin of phaeochromocytoma. Mutation screening confirmed a germline mutation of the transmembrane protein 127 tumorsupressor gene in both patients. Both patients underwent cortical-sparing adrenalectomy. The adrenal gland with the larger tumor was totally resected, while in the opposite side only the tumor was resected and a small part of the cortex was saved. After the operation urinary catecholamines and serum chromogranin A returned to normal in both patients. Adrenocortical deficiency was absent in the first patient, but her sister developed adrenal insufficiency requiring glucocorticoid replacement. To the best of the authors' knowledge phaeochromocytoma affecting twins has never been described earlier. Genetic examination performed in siblings confirmed the presence of the mutant gene through four generations. Orv. Hetil., 2016, 157(33), 1326-1330.

  13. [Advances in hereditary hemochromatosis].

    Science.gov (United States)

    Nardi, Graciela; Cadiz, Claudia; Lachman, J; Cornelio, Cecilia

    2003-01-01

    Hereditary hemocromatosis (HH) is a genetic disease with a recessive autosomic pattern, in which inadequate iron (Fe) absorption is made by the intestinal cell. As consequence of that process, takes place a progressive accumulation of metal in different organs, predominantly in the liver. This leads to an alteration of liver structure and function: cirrhosis and hepatocarcinoma (1). The gene implied in this pathology was identified (HFE) in 1996. This codes a similar molecule to the mayor histocompatibility complex type 1(MHC-T1 like) that can modulate the transport of PE binding the transferrin receptor. This progress allows a deep understanding of the molecular and cellular biology of the homeostasis of the Fe and its alterations in the NH. The diagnosis of disease by means of a genetic test let to carry out a familiar screening and to detect asymptomatic carriers. This makes possible to begin the appropriate treatment at early stages of the disease in order to avoid its consequences and offering a better quality of life to these patients.

  14. Adult hereditary fructose intolerance

    Institute of Scientific and Technical Information of China (English)

    Mohamed Ismail Yasawy; Ulrich Richard Folsch; Wolfgang Eckhard Schmidt; Michael Schwend

    2009-01-01

    Hereditary fructose intolerance (HFI) is an underrecognized,preventable life-threatening condition. It is an autosomal recessive disorder with subnormal activity of aldolase B in the liver, kidney and small bowel. Symptoms are present only after the ingestion of fructose, which leads to brisk hypoglycemia, and an individual with continued ingestion will exhibit vomiting,abdominal pain, failure to thrive, and renal and liver failure. A diagnosis of HFI was made in a 50-year-old woman on the basis of medical history, response to Ⅳ fructose intolerance test, demonstration of aldolase B activity reduction in duodenal biopsy, and molecular analysis of leukocyte DNA by PCR showed homozygosity for two doses of mutant gene. HFI may remain undiagnosed until adult life and may lead to disastrous complications following inadvertent fructose or sorbitol infusion. Several lethal episodes of HFI following sorbitol and fructose infusion have been reported. The diagnosis can only be suspected by taking a careful dietary history, and this can present serious complications.

  15. Adult hereditary fructose intolerance.

    Science.gov (United States)

    Yasawy, Mohamed Ismail; Folsch, Ulrich Richard; Schmidt, Wolfgang Eckhard; Schwend, Michael

    2009-05-21

    Hereditary fructose intolerance (HFI) is an under-recognized, preventable life-threatening condition. It is an autosomal recessive disorder with subnormal activity of aldolase B in the liver, kidney and small bowel. Symptoms are present only after the ingestion of fructose, which leads to brisk hypoglycemia, and an individual with continued ingestion will exhibit vomiting, abdominal pain, failure to thrive, and renal and liver failure. A diagnosis of HFI was made in a 50-year-old woman on the basis of medical history, response to IV fructose intolerance test, demonstration of aldolase B activity reduction in duodenal biopsy, and molecular analysis of leukocyte DNA by PCR showed homozygosity for two doses of mutant gene. HFI may remain undiagnosed until adult life and may lead to disastrous complications following inadvertent fructose or sorbitol infusion. Several lethal episodes of HFI following sorbitol and fructose infusion have been reported. The diagnosis can only be suspected by taking a careful dietary history, and this can present serious complications.

  16. Chaperonopathies: Spotlight on Hereditary Motor Neuropathies.

    Science.gov (United States)

    Lupo, Vincenzo; Aguado, Carmen; Knecht, Erwin; Espinós, Carmen

    2016-01-01

    Distal hereditary motor neuropathies (dHMN) are a group of rare hereditary neuromuscular disorders characterized by an atrophy that affects peroneal muscles in the absence of sensory symptoms. To date, 23 genes are thought to be responsible for dHMN, four of which encode chaperones: DNAJB2, which encodes a member of the HSP40/DNAJ co-chaperone family; and HSPB1, HSPB3, and HSPB8, encoding three members of the small heat shock protein family. While around 30 different mutations in HSPB1 have been identified, the remaining three genes are altered in many fewer cases. Indeed, a mutation of HSPB3 has only been described in one case, whereas a few cases have been reported carrying mutations in DNAJB2 and HSPB8, most of them caused by a founder c.352+1G>A mutation in DNAJB2 and by mutations affecting the K141 residue in the HSPB8 chaperone. Hence, their rare occurrence makes it difficult to understand the pathological mechanisms driven by such mutations in this neuropathy. Chaperones can assemble into multi-chaperone complexes that form an integrated chaperone network within the cell. Such complexes fulfill relevant roles in a variety of processes, such as the correct folding of newly synthesized proteins, in which chaperones escort them to precise cellular locations, and as a response to protein misfolding, which includes the degradation of proteins that fail to refold properly. Despite this range of functions, mutations in some of these chaperones lead to diseases with a similar clinical profile, suggesting common pathways. This review provides an overview of the genetics of those dHMNs that share a common disease mechanism and that are caused by mutations in four genes encoding chaperones: DNAJB2, HSPB1, HSPB3, and HSPB8.

  17. Chaperonopathies: spotlight on hereditary motor neuropathies

    Directory of Open Access Journals (Sweden)

    Vincenzo Lupo

    2016-12-01

    Full Text Available Distal hereditary motor neuropathies (dHMN comprise a group of rare hereditary neuromuscular disorders characterized by a peroneal muscular atrophy without sensory symptoms. To date twenty-three genes for dHMN have been reported and four of them encode for chaperones: DNAJB2, which encodes a member of the HSP40/DNAJ co-chaperone family, and HSPB1, HSPB3 and HSPB8, which encode three members of the family of small heat shock proteins. Except for HSPB1, with around thirty different mutations, the remaining three genes comprise a much low number of cases. Thus, only one case has been described caused by an HSPB3 mutation, whereas few DNAJB2 and HSPB8 cases are known, most of them caused by a founder c.352+1G>A mutation in DNAJB2 and by mutations affecting the hot spot K141 residue of the HSPB8 chaperone. This low number of cases makes it difficult to understand the pathomechanism underlying the neuropathy. Chaperones can assemble in multi-chaperone complexes forming an integrative chaperone network in the cell, which plays relevant cellular roles in a variety of processes such as the correct folding of newly synthesized proteins, their escort to their precise cellular locations to form functional proteins and complexes and the response to protein misfolding, including the degradation of proteins that fail to refold properly. Despite of this variety of functions, mutations in some of them lead to diseases with a similar clinical picture, suggesting common pathways. This review gives an overview of the genetics of dHMNs caused by mutations in four genes, DNAJB2, HSPB1, HSPB3 and HSPB8, which encode chaperones and show a common disease mechanism.

  18. Chaperonopathies: Spotlight on Hereditary Motor Neuropathies

    Science.gov (United States)

    Lupo, Vincenzo; Aguado, Carmen; Knecht, Erwin; Espinós, Carmen

    2016-01-01

    Distal hereditary motor neuropathies (dHMN) are a group of rare hereditary neuromuscular disorders characterized by an atrophy that affects peroneal muscles in the absence of sensory symptoms. To date, 23 genes are thought to be responsible for dHMN, four of which encode chaperones: DNAJB2, which encodes a member of the HSP40/DNAJ co-chaperone family; and HSPB1, HSPB3, and HSPB8, encoding three members of the small heat shock protein family. While around 30 different mutations in HSPB1 have been identified, the remaining three genes are altered in many fewer cases. Indeed, a mutation of HSPB3 has only been described in one case, whereas a few cases have been reported carrying mutations in DNAJB2 and HSPB8, most of them caused by a founder c.352+1G>A mutation in DNAJB2 and by mutations affecting the K141 residue in the HSPB8 chaperone. Hence, their rare occurrence makes it difficult to understand the pathological mechanisms driven by such mutations in this neuropathy. Chaperones can assemble into multi-chaperone complexes that form an integrated chaperone network within the cell. Such complexes fulfill relevant roles in a variety of processes, such as the correct folding of newly synthesized proteins, in which chaperones escort them to precise cellular locations, and as a response to protein misfolding, which includes the degradation of proteins that fail to refold properly. Despite this range of functions, mutations in some of these chaperones lead to diseases with a similar clinical profile, suggesting common pathways. This review provides an overview of the genetics of those dHMNs that share a common disease mechanism and that are caused by mutations in four genes encoding chaperones: DNAJB2, HSPB1, HSPB3, and HSPB8. PMID:28018906

  19. Treatment of hereditary optic neuropathies.

    Science.gov (United States)

    Newman, Nancy J

    2012-10-01

    The hereditary optic neuropathies are inherited disorders in which optic nerve dysfunction is a prominent feature in the phenotypic expression of disease. Optic neuropathy may be primarily an isolated finding, such as in Leber hereditary optic neuropathy and dominant optic atrophy, or part of a multisystem disorder. The pathophysiological mechanisms underlying the hereditary optic neuropathies involve mitochondrial dysfunction owing to mutations in mitochondrial or nuclear DNA that encodes proteins essential to mitochondrial function. Effective treatments are limited, and current management includes therapies directed at enhancing mitochondrial function and preventing oxidative damage, as well as genetic counselling, and supportive and symptomatic measures. New therapies, including gene therapy, are emerging via animal models and human clinical trials. Leber hereditary optic neuropathy, in particular, provides a unique model for testing promising treatments owing to its characteristic sequential bilateral involvement and the accessibility of target tissue within the eye. Lessons learned from treatment of the hereditary optic neuropathies may have therapeutic implications for other disorders of presumed mitochondrial dysfunction. In this Review, the natural history of the common inherited optic neuropathies, the presumed pathogenesis of several of these disorders, and the literature to date regarding potential therapies are summarized.

  20. Hereditary pancreatitis: current perspectives

    Directory of Open Access Journals (Sweden)

    Raphael KL

    2016-07-01

    Full Text Available Kara L Raphael, Field F Willingham Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA Abstract: Hereditary pancreatitis (HP is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy. Keywords: pancreatic cancer, chronic pancreatitis, idiopathic pancreatitis, pancreatitis, familial pancreatitis, genetic mutations

  1. An update on hereditary angioedema.

    Science.gov (United States)

    Verdi, Marylee; Shaker, Marcus

    2011-01-01

    Hereditary angioedema affects approximately 1 in 50,000 individuals without gender or ethnic preference. Hereditary angioedema is caused by a decreased level (type I) or function (type II) of C1 inhibitor. Patients experience repeated episodes of angioedema involving sites that include the face, extremities, gastrointestinal tract, and larynx. Treatment involves measures to increase functioning levels of active C1 inhibitor through stimulation of endogenous pathways or exogenous supplementation. Additional therapies targeted at inhibition of bradykinin can also be used to treat episodes of angioedema. Treatment may be indicated for both acute episodes of angioedema and prevention of future episodes.

  2. [Diagnosis of the peripheral hereditary neuropathies and its molecular genetics].

    Science.gov (United States)

    Hernández-Zamora, Edgar; Arenas-Sordo, María de la Luz

    2008-01-01

    Peripheral neuropathies include a wide range of pathological disorders characterized by damage of peripheral nerves. Among them, peripheral hereditary neuropathies are a group of frequent illnesses and early evolution. They have been named hereditary motor and sensory neuropathy (HMSN) or peripheral hereditary neuropathies type Charcot-Marie-Tooth (CMT). The most frequent types are CMT1, CMT2 and CMTX. Approximately 70% of the cases correspond to subtype CMT1A, associated with tandem duplication of a 1.5 Mb DNA fragment on chromosome 17p11.2-p12 that codifies the peripheral myelin protein PMP22. So far, there five different types of CMT (1,2,3,4,X) with approximately 32 subtypes, associated with more than 30 genes. Have been reported genetic heterogeneity and expression variability of the illness makes it necessary to carry on diagnostic strategies that integrate clinical study for determining genetic clinical history, family history, complete physical exploration, muscular strength, physical deformities, reflexes and sensitivity, and molecular studies allow detection of different types of mutations and help establish a correct diagnosis and an adequate genetic counseling.

  3. [Hereditary fructose intolerance (author's transl)].

    Science.gov (United States)

    Thanner, F

    1977-07-01

    Hereditary fructose intolerance (HFI) is the most important disturbance in human fructose metabolism. This paper deals with the present knowledge of biochemistry and pathophysiology of this inborn error of metabolism, which is often wrongly diagnosed and gives a detailed description of diagnostic and therapeutic procedures.

  4. Hereditary skin diseases of hemidesmosomes

    NARCIS (Netherlands)

    Jonkman, MF

    1999-01-01

    Studies of hereditary blistering skin diseases (epidermolysis bullosa) and targeted gene mutation experiments in knockout mice have greatly improved our understanding of hemidesmosomes and their associated structures in the cytoskeleton and basement membrane of the skin and mucous membranes. At leas

  5. Drug therapy for hereditary cancers

    Directory of Open Access Journals (Sweden)

    Imyanitov Evgeny N

    2011-08-01

    Full Text Available Abstract Tumors arising in patients with hereditary cancer syndromes may have distinct drug sensitivity as compared to their sporadic counterparts. Breast and ovarian neoplasms from BRCA1 or BRCA2 mutation carriers are characterized by deficient homologous recombination (HR of DNA, that makes them particularly sensitive to platinum compounds or inhibitors of poly (ADP-ribose polymerase (PARP. Outstandingly durable complete responses to high dose chemotherapy have been observed in several cases of BRCA-related metastatic breast cancer (BC. Multiple lines of evidence indicate that women with BRCA1-related BC may derive less benefit from taxane-based treatment than other categories of BC patients. There is virtually no reports directly assessing drug response in hereditary colorectal cancer (CRC patients; studies involving non-selected (i.e., both sporadic and hereditary CRC with high-level microsatellite instability (MSI-H suggest therapeutic advantage of irinotecan. Celecoxib has been approved for the treatment of familial adenomatous polyposis (FAP. Hereditary medullary thyroid cancers (MTC have been shown to be highly responsive to a multitargeted tyrosine kinase inhibitor vandetanib, which exerts specific activity towards mutated RET receptor. Given the rapidly improving accessibility of DNA analysis, it is foreseen that the potential predictive value of cancer-associated germ-line mutations will be increasingly considered in the future studies.

  6. Genetics of Hereditary Angioedema Revisited.

    Science.gov (United States)

    Germenis, Anastasios E; Speletas, Matthaios

    2016-10-01

    Contemporary genetic research has provided evidences that angioedema represents a diverse family of disorders related to kinin metabolism, with a much greater genetic complexity than was initially considered. Convincing data have also recently been published indicating that the clinical heterogeneity of hereditary angioedema due to C1 inhibitor deficiency (classified as C1-INH-HAE) could be attributed at least in part, either to the type of SERPING1 mutations or to mutations in genes encoding for enzymes involved in the metabolism and function of bradykinin. Alterations detected in at least one more gene (F12) are nowadays considered responsible for 25 % of cases of hereditary angioedema with normal C1-INH (type III hereditary angioedema (HAE), nlC1-INH-HAE). Interesting data derived from genetic approaches of non-hereditary angioedemas indicate that other immune pathways might be implicated in the pathogenesis of HAE. More than 125 years after the recognition of the hereditary nature of HAE by Osler, the heterogeneity of clinical expressions, the genetics of this disorder, and the genotype-phenotype relationships, still presents a challenge that will be discussed in this review. Large scale, in-depth genetic studies are expected not only to answer these emerging questions but also to further elucidate many of the unmet aspects of angioedema pathogenesis. Uncovering genetic biomarkers affecting the severity of the disease and/or the effectiveness of the various treatment modalities might lead to the prevention of attacks and the optimization of C1-INH-HAE management that is expected to provide a valuable benefit to the sufferers of angioedema.

  7. Hip dysplasia associated with a hereditary sensorimotor polyneuropathy mimics a myopathic process

    Directory of Open Access Journals (Sweden)

    Mohammad Javad Hadianfard

    2012-01-01

    Full Text Available Some orthopedic complications have been reported in the hereditary neuropathies. However, the association of the hip dysplasia with this category of neuropathy is rarely recognized. We present a 13-year-old boy with the progressive weakness of the lower extremities, difficulty in walking, climbing stairs, and rising from floor; a wide-based, hyper-extended and waddling gait similar to a myopathic process. Hip radiography showed dysplastic acetabulae with hip subluxation, broken Shenton′s lines, and valgus femoral necks. In electrodiagnosis, there was a significant neuropathic process (absent all evoked sensory potentials, abnormal evoked motor responses, and neurogenic electeromyography which eventually was found to be a hereditary mixed axonal and demyelinating sensorimotor polyneuropathy with concomitant hip dysplasia confirmed with thorough physical examination and the electrodiagnostic study. In patients with gait difficulties such as waddling gait mimicking a myopathic process, hereditary polyneuropathy complicated with hip dysplasia should be considered as well.

  8. Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by fatigue, ischemia and low temperature

    Science.gov (United States)

    Brunetti, Orazio; Imbrici, Paola; Botti, Fabio Massimo; Pettorossi, Vito Enrico; D'Adamo, Maria Cristina; Valentino, Mario; Zammit, Christian; Mora, Marina; Gibertini, Sara; Di Giovanni, Giuseppe; Muscat, Richard; Pessia, Mauro

    2012-01-01

    Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by myokymia and attacks of ataxic gait often precipitated by stress. Several genetic mutations have been identified in the Shaker-like K+ channel Kv1.1 (KCNA1) of EA1 individuals, including V408A, which result in remarkable channel dysfunction. By inserting the heterozygous V408A, mutation in one Kv1.1 allele, a mouse model of EA1 has been generated (Kv1.1V408A/+). Here, we investigated the neuromuscular transmission of Kv1.1V408A/+ ataxic mice and their susceptibility to physiologically relevant stressors. By using in vivo preparations of lateral gastrocnemius (LG) nerve–muscle from Kv1.1+/+ and Kv1.1V408A/+ mice, we show that the mutant animals exhibit spontaneous myokymic discharges consisting of repeated singlets, duplets or multiplets, despite motor nerve axotomy. Two-photon laser scanning microscopy from the motor nerve, ex vivo, revealed spontaneous Ca2 + signals that occurred abnormally only in preparations dissected from Kv1.1V408A/+ mice. Spontaneous bursting activity, as well as that evoked by sciatic nerve stimulation, was exacerbated by muscle fatigue, ischemia and low temperatures. These stressors also increased the amplitude of compound muscle action potential. Such abnormal neuromuscular transmission did not alter fiber type composition, neuromuscular junction and vascularization of LG muscle, analyzed by light and electron microscopy. Taken together these findings provide direct evidence that identifies the motor nerve as an important generator of myokymic activity, that dysfunction of Kv1.1 channels alters Ca2 + homeostasis in motor axons, and also strongly suggest that muscle fatigue contributes more than PNS fatigue to exacerbate the myokymia/neuromyotonia phenotype. More broadly, this study points out that juxtaparanodal K+ channels composed of Kv1.1 subunits exert an important role in dampening the excitability of motor nerve axons during fatigue or

  9. New treatments of hereditary blindness

    DEFF Research Database (Denmark)

    Bertelsen, Mette; Rosenberg, Thomas; Larsen, Michael

    2013-01-01

    Ongoing clinical trials are targeting several previously intractable hereditary causes of blindness of congenital, childhood or early adulthood onset, mainly in the optic nerve and retina. The intended stage of initiation of the new therapeutic approaches ranges from neonatal life and a structura......Ongoing clinical trials are targeting several previously intractable hereditary causes of blindness of congenital, childhood or early adulthood onset, mainly in the optic nerve and retina. The intended stage of initiation of the new therapeutic approaches ranges from neonatal life...... and a structurally intact retinal tissue to adult life with a complete loss of photoreceptors. It must be assumed that some of the trials will succeed in producing new therapies and action must be taken to refine and accelerate diagnostics and to preserve therapeutic potential in blind people....

  10. Bilateral dissociated vertical deviation in a case of congenital hereditary endothelial dystrophy

    Directory of Open Access Journals (Sweden)

    Bhola Rahul

    2006-01-01

    Full Text Available Dissociated vertical deviation (DVD is an intermittent anomaly of the non-fixing eye. Although association of DVD with sensory visual deprivation owing to congenital or acquired opacities of the ocular media has been reported, its association with congenital hereditary endothelial dystrophy (CHED has not been reported hitherto. We report a case having a bilateral asymmetric DVD, in a know case of bilateral CHED.

  11. Overlapping molecular pathological themes link Charcot-Marie-Tooth neuropathies and hereditary spastic paraplegias.

    Science.gov (United States)

    Timmerman, Vincent; Clowes, Virginia E; Reid, Evan

    2013-08-01

    In this review we focus on Charcot-Marie-Tooth (CMT) neuropathies and hereditary spastic paraplegias (HSPs). Although these diseases differ in whether they primarily affect the peripheral or central nervous system, both are genetically determined, progressive, long axonopathies that affect motor and sensory pathways. This commonality suggests that there might be similarities in the molecular pathology underlying these conditions, and here we compare the molecular genetics and cellular pathology of the two groups.

  12. An overview of hereditary pancreatitis.

    Science.gov (United States)

    Rebours, Vinciane; Lévy, Philippe; Ruszniewski, Philippe

    2012-01-01

    Hereditary pancreatitis is a rare cause of chronic pancreatitis. The prevalence was evaluated to 0.3/100000 in Western Countries. Genetic disorders are due to mutations of the PRSS1 gene on the long arm of the chromosome 7, encoding for the cationic trypsinogen. The inheritance pattern is autosomal dominant with an incomplete penetrance (80%). Since 1996, more than 30 mutations were found. The three more common mutations are R122H, N29I and A16V. First symptoms begin since childhood, mainly before 10 years old. Main symptoms are pancreatic pain and acute pancreatitis (>70%). CP morphological changes as pancreatic calcifications are diagnosed at a median age of 22-25 years. Exocrine and endocrine pancreatic insufficiency occurred in 34% and 26% at a median age of 29 and 38 years. No clinical differences exist according to the mutation type. No excess of mortality in hereditary pancreatitis population compared to general population was found, despite a real risk of cancer. The cumulative risks of pancreatic cancer at 50, 60 and, 75 years are 10%, 18.7% and, 53.5%, respectively. The relative risk of cancer increases in smokers and is evaluated to 8.55. Hereditary pancreatitis diagnosis permits to propose an adapted management in expert centres.

  13. Hereditary angioedema may not be the only cause of abdominal pain in patients with hereditary angioedema!

    OpenAIRE

    Ozgur Kartal; Sevket Arslan; Mustafa Gulec; Ahmet Zafer Caliskaner; Abdullah Baysan; Nail Ersoz; Ugur Musabak; Osman Sener

    2016-01-01

    Abdominal pain is one of the basic clinical presentations of the hereditary angioedema and danazol is a common medicine which has been used for long years in patients with hereditary angioedema. We present two hereditary angioedema patients with abdominal pain albeit under danazol treatment, whose final diagnoses was colon carcinoma. There are two consequences in this article which shall be insisted on: First; in patients with hereditary angioedema, the differential diagnosis of and ldquo;ab...

  14. Charcot-Marie-Tooth Disease and Related Hereditary Neuropathies: From Gene Function to Associated Phenotypes.

    Science.gov (United States)

    Pareyson, D; Saveri, P; Piscosquito, G

    2014-10-10

    Charcot-Marie-Tooth disease (CMT) and related neuropathies are a genetically highly heterogeneous group of neurodegenerative disorders. CMT affects both the sensory and motor nerves, distal Hereditary Motor Neuropathies (dHMN) are phenotypically similar disorders involving only motor nerves, while Hereditary Sensory and Autonomic Neuropathies (HSAN) are rare distinct disorders affecting sensory and sometimes autonomic nerves. Almost 70 genes have been identified as responsible for these disorders. It is astonishing to learn how diverse are the cellular sublocalisation and the functional roles of the encoded proteins of CMT-associated genes which all lead to similar disorders of the peripheral nervous system. Myelin formation and maintenance, mitochondrial dynamics, cytoskeleton organization, axonal transport, and vesicular trafficking are the most frequently involved pathways. However, dysfunction of several activities from the nucleus to the neuromuscular junction forms the basis for these hereditary neuropathies, making it challenging predicting the functions of newly identified mutated genes. In this review we will discuss the function and related phenotypes of all the genes thus far associated with CMT, dHMN, and HSAN.

  15. Inherited focal, episodic neuropathies: hereditary neuropathy with liability to pressure palsies and hereditary neuralgic amyotrophy.

    Science.gov (United States)

    Chance, Phillip F

    2006-01-01

    Hereditary neuropathy with liability to pressure palsies (HNPP; also called tomaculous neuropathy) is an autosomal-dominant disorder that produces a painless episodic, recurrent, focal demyelinating neuropathy. HNPP generally develops during adolescence, and may cause attacks of numbness, muscular weakness, and atrophy. Peroneal palsies, carpal tunnel syndrome, and other entrapment neuropathies may be frequent manifestations of HNPP. Motor and sensory nerve conduction velocities may be reduced in clinically affected patients, as well as in asymptomatic gene carriers. The histopathological changes observed in peripheral nerves of HNPP patients include segmental demyelination and tomaculous or "sausage-like" formations. Mild overlap of clinical features with Charcot-Marie-Tooth (CMT) disease type 1 (CMT1) may lead patients with HNPP to be misdiagnosed as having CMT1. HNPP and CMT1 are both demyelinating neuropathies, however, their clinical, pathological, and electrophysiological features are quite distinct. HNPP is most frequently associated with a 1.4-Mb pair deletion on chromosome 17p12. A duplication of the identical region leads to CMT1A. Both HNPP and CMT1A result from a dosage effect of the PMP22 gene, which is contained within the deleted/duplicated region. This is reflected in reduced mRNA and protein levels in sural nerve biopsy samples from HNPP patients. Treatment for HNPP consists of preventative and symptom-easing measures. Hereditary neuralgic amyotrophy (HNA; also called familial brachial plexus neuropathy) is an autosomal-dominant disorder causing episodes of paralysis and muscle weakness initiated by severe pain. Individuals with HNA may suffer repeated episodes of intense pain, paralysis, and sensory disturbances in an affected limb. The onset of HNA is at birth or later in childhood with prognosis for recovery usually favorable; however, persons with HNA may have permanent residual neurological dysfunction following attack(s). Episodes are often

  16. Genetics Home Reference: hereditary antithrombin deficiency

    Science.gov (United States)

    ... Merck Manual Home Edition for Patients and Caregivers: Thrombophilia National Blood Clot Alliance: Antithrombin Deficiency Orphanet: Hereditary thrombophilia due to congenital antithrombin deficiency Patient Support and ...

  17. Idiopathic Thrombocytopenic Purpura Misdiagnosed as Hereditary Angioedema

    DEFF Research Database (Denmark)

    Andersen, Michelle Fog; Bygum, Anette

    2015-01-01

    Hereditary angioedema is a rare, but potentially life-threatening genetic disorder that results from an autosomal dominant trait. It is characterized by acute, recurrent attacks of severe local edema, most commonly affecting the skin and mucosa. Swelling in hereditary angioedema patients does...... however not always have to be caused by angioedema but can relate to other concomitant disorders. In this report we are focusing on misdiagnosis in a patient with known hereditary angioedema, whose bleeding episode caused by idiopathic thrombocytopenic purpura was mistaken for an acute attack...... of hereditary angioedema. The case illustrates how clinicians can have difficulties in handling patients with rare diseases, especially in the emergency care setting....

  18. Genetics Home Reference: hereditary fructose intolerance

    Science.gov (United States)

    ... Additional Information & Resources MedlinePlus (2 links) Encyclopedia: Hereditary Fructose Intolerance Health Topic: Carbohydrate Metabolism Disorders Genetic and Rare Diseases Information Center (1 ...

  19. "Congenital Sensory Neuropathy as a Differential Diagnosis for Phagocytic Immunodeficiency "

    Directory of Open Access Journals (Sweden)

    Mohammad Gharagozlou

    2006-03-01

    Full Text Available There are few reports about congenital indifference to pain or Hereditary and Sensory Autonomic Neuropathy (HSAN. Several investigations for pathophysiology of this syndrome have been performed and different classifications about it. In this report we present a case of HSAN type II with general absence of pain and self amputations and leprosy–like damage of extremities which was suspected to be phagocytic immunodeficiency due to past history of repeated ulcer and abscess formation.

  20. A KCNJ10 mutation previously identified in the Russell group of terriers also occurs in Smooth-Haired Fox Terriers with hereditary ataxia and in related breeds.

    Science.gov (United States)

    Rohdin, Cecilia; Gilliam, Douglas; O'Leary, Caroline A; O'Brien, Dennis P; Coates, Joan R; Johnson, Gary S; Jäderlund, Karin Hultin

    2015-05-23

    Hereditary ataxias with similar phenotypes were reported in the Smooth-Haired Fox Terrier, the Jack Russell Terrier and the Parson Russell Terrier. However, segregation analyses showed differing inheritance modes in these breeds. Recently, molecular genetic studies on the Russell group of terriers found independent mutations in KCNJ10 and CAPN1, each associated with a specific clinical subtype of inherited ataxia. The aim of this study was to clarify whether or not Smooth-Haired Fox Terriers with hereditary ataxia and dogs of other related breeds harbor either of the same mutations. A sub goal was to update the results of KCNJ10 genotyping in Russell group terriers. Three Smooth-Haired Fox Terriers with hereditary ataxia and two Toy Fox Terriers with a similar phenotype were all homozygous for the KCNJ10 mutation. The same mutation was also found in a heterozygous state in clinically unaffected Tenterfield Terriers (n = 5) and, in agreement with previous studies, in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers. A KCNJ10 mutation, previously associated with an autosomal recessive spinocerebellar ataxia in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers segregates in at least three more breeds descended from British hunting terriers. Ataxic members of two of these breeds, the Smooth-Haired Fox Terrier and the Toy Fox Terrier, were homozygous for the mutation, strengthening the likelihood that this genetic defect is indeed the causative mutation for the disease known as "hereditary ataxia" in Fox Terriers and "spinocerebellar ataxia with myokymia, seizures or both" in the Russell group of terriers.

  1. Role of stretch therapy in comprehensive physical habilitation of patients with Charcot–Marie–Tooth hereditary neuropathy

    Directory of Open Access Journals (Sweden)

    N. A. Shnayder

    2015-01-01

    Full Text Available Charcot–Marie–Tooth hereditary neuropathy (Charcot–Marie–Tooth disease, CMT is the most common form of hereditary neuropathies, accompanied by sensory disorders, progressive muscle weakness with the formation of disabling contractures of the limbs. Currently, the main treatment program is effective CMT habilitation, which can prevent the development of limb deformities and thereby improve the life quality of the patient. Stretch therapy is one of the most effective methods of prevention and treatment of contractures in patients with CMT. This article provides a brief review of the literature regarding the use of stretching as physical therapy program of CMT habilitation.

  2. Hereditary breast and ovarian cancer

    DEFF Research Database (Denmark)

    Nielsen, Finn Cilius; Hansen, Thomas van Overeem; Sørensen, Claus Storgaard

    2016-01-01

    Genetic abnormalities in the DNA repair genes BRCA1 and BRCA2 predispose to hereditary breast and ovarian cancer (HBOC). However, only approximately 25% of cases of HBOC can be ascribed to BRCA1 and BRCA2 mutations. Recently, exome sequencing has uncovered substantial locus heterogeneity among...... affected families without BRCA1 or BRCA2 mutations. The new pathogenic variants are rare, posing challenges to estimation of risk attribution through patient cohorts. In this Review article, we examine HBOC genes, focusing on their role in genome maintenance, the possibilities for functional testing...... of putative causal variants and the clinical application of new HBOC genes in cancer risk management and treatment decision-making....

  3. Two cases of hereditary fructose intolerance.

    Science.gov (United States)

    Ananth, N; Praveenkumar, G S; Rao, K Aravind; Vasanthi; Kakkilaya, Srinivas

    2003-07-01

    Hereditary fructose intolerance is a rare cause of hepatic cirrhosis in the young. The disorder has a reported frequency of 1 in 20000 live births and no case has been reported from India so far. We report two cases of hereditary fructose intolerance, both with bilateral cataracts and one with cirrhosis of the liver.

  4. [Review of the recent literature on hereditary neuropathies].

    Science.gov (United States)

    Birouk, N

    2014-12-01

    The recent literature included interesting reports on the pathogenic mechanisms of hereditary neuropathies. The axonal traffic and its abnormalities in some forms of Charcot-Marie-Tooth (CMT) disease were particularly reviewed by Bucci et al. Many genes related to CMT disease code for proteins that are involved directly or not in intracellular traffic. KIF1B controls vesicle motility on microtubules. MTMR2, MTMR13 and FIG4 regulate the metabolism of phosphoinositide at the level of endosomes. The HSPs are involved in the proteasomal degradation. GDAP1 and MFN2 regulate the mitochondrial fission and fusion respectively and the mitochondial transport within the axon. Pareyson et al. reported a review on peripheral neuropathies in mitochondrial disorders. They used the term of "mitochondrial CMT" for the forms of CMT with abnormal mitochondrial dynamic or structure. Among the new entities, we can draw the attention to a proximal form of hereditary motor and sensory neuropathy with autosomal dominant inheritance, which is characterized by motor deficit with cramps and fasciculations predominating in proximal muscles. Distal sensory deficit can be present. The gene TFG on chromosome 3 has been recently identified to be responsible for this form. Another rare form of axonal autosomal recessive neuropathy due to HNT1 gene mutation is characterized by the presence of hands myotonia that appears later than neuropathy but constitute an interesting clinical hallmark to orientate the diagnosis of this form. In terms of differential diagnosis, CMT4J due to FIG4 mutation can present with a rapidly progressive and asymmetric weakness that resembles CIDP. Bouhy et al. made an interesting review on the therapeutic trials, animal models and the future therapeutic strategies to be developed in CMT disease.

  5. Experimental therapeutics in hereditary neuropathies: the past, the present, and the future.

    Science.gov (United States)

    Herrmann, David N

    2008-10-01

    Hereditary neuropathies represent approximately 40% of undiagnosed neuropathies in a tertiary clinic setting. The Charcot-Marie-Tooth neuropathies (CMT) are the most common. Mutations in more than 40 genes have been identified to date in CMT. Approximately 50% of CMT cases are accounted for by CMT type 1A, due to a duplication within the peripheral myelin protein 22 gene (PMP22). Mutations in the gap junction beta 1 gene (GJB1), the myelin protein zero gene (MPZ), and the mitofusin 2 gene (MFN2) account for a substantial proportion of other genetically definable CMT. Some 15% of demyelinating CMT and 70% of axonal CMT await genetic clarification. Other hereditary neuropathies include the hereditary sensory and autonomic neuropathies, the familial amyloid polyneuropathies, and multisystem disorders (e.g., lipid storage diseases and inherited ataxias) that have peripheral neuropathy as a major or minor component. This review surveys the challenges of developing effective therapies for hereditary neuropathies in terms of past, present, and future experimental therapeutics in CMT.

  6. Genetics 101 --The Hereditary Material of Life

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Genetics 101 Genetics 101 — The Hereditary Material of Life Past Issues / Summer 2013 Table of Contents Genetics is the study of heredity, the process in ...

  7. Hereditary angioedema: imaging manifestations and clinical management.

    Science.gov (United States)

    Gakhal, Mandip S; Marcotte, Gregory V

    2015-02-01

    Hereditary angioedema is a genetic disorder typically related to insufficient or dysfunctional C1-esterase inhibitor. Patients present with episodic swelling of various body parts, such as the face, neck, bowel, genitals, and extremities. Acute or severe symptoms can lead to patients presenting to the emergency room, particularly when the neck and abdominopelvic regions are affected, which is often accompanied by radiologic imaging evaluation. Patients with hereditary angioedema can pose a diagnostic challenge for emergency department physicians and radiologists at initial presentation, and the correct diagnosis may be missed or delayed, due to lack of clinical awareness of the disease or lack of its consideration in the radiologic differential diagnosis. Timely diagnosis of hereditary angioedema and rapid initiation of appropriate therapy can avoid potentially life-threatening complications. This article focuses on the spectrum of common and characteristic acute imaging manifestations of hereditary angioedema and provides an update on important recent developments in its clinical management and treatment.

  8. Idiopathic Thrombocytopenic Purpura Misdiagnosed as Hereditary Angioedema

    Directory of Open Access Journals (Sweden)

    Michelle Fog Andersen

    2015-01-01

    Full Text Available Hereditary angioedema is a rare, but potentially life-threatening genetic disorder that results from an autosomal dominant trait. It is characterized by acute, recurrent attacks of severe local edema, most commonly affecting the skin and mucosa. Swelling in hereditary angioedema patients does however not always have to be caused by angioedema but can relate to other concomitant disorders. In this report we are focusing on misdiagnosis in a patient with known hereditary angioedema, whose bleeding episode caused by idiopathic thrombocytopenic purpura was mistaken for an acute attack of hereditary angioedema. The case illustrates how clinicians can have difficulties in handling patients with rare diseases, especially in the emergency care setting.

  9. Hereditary History Preserving Bisimilarity Is Undecidable

    DEFF Research Database (Denmark)

    Jurdzinski, Marcin; Nielsen, Mogens

    2000-01-01

    History preserving bisimilarity (hp-bisimilarity) and hereditary history preserving bisimilarity (hhp-bisimilarity) are behavioural equivalences taking into account causal relationships between events of concurrent systems. Their prominent feature is being preserved under action refinement...

  10. Splenic Involvement in Hereditary Hemorrhagic Telangiectasia

    Directory of Open Access Journals (Sweden)

    Susumu Takamatsu

    2016-01-01

    Full Text Available A 33-year-old man who presented with prolonged epigastric pain was referred to our hospital. He had experienced recurrent epistaxis and had a family history of hereditary hemorrhagic telangiectasia. Computed tomography and magnetic resonance imaging revealed splenomegaly and a 9 cm hypervascular mass in his spleen. Computed tomography also showed a pulmonary arteriovenous malformation and heterogeneous enhancement of the liver parenchyma, suggesting the presence of arteriosystemic shunts and telangiectases. Based on these findings, the patient was definitely diagnosed with hereditary hemorrhagic telangiectasia according to Curaçao criteria. He underwent splenectomy, and his symptoms disappeared after surgery. Pathological examination of the resected specimen revealed that the hypervascular lesion of the spleen was not a tumor but was composed of abnormal vessels associated with hereditary hemorrhagic telangiectasia. Symptomatic splenic involvement may be a rare manifestation of hereditary hemorrhagic telangiectasia but can be revealed by imaging modalities.

  11. Genetics Home Reference: hereditary cerebral amyloid angiopathy

    Science.gov (United States)

    ... Neubert TA, Lu Y, Rebeck GW, Frangione B, Greenberg SM, Ghiso J. Iowa variant of familial Alzheimer's ... ML, van Duinen SG, Roos RA, Frosch MP, Greenberg SM. The cerebral beta-amyloid angiopathies: hereditary and ...

  12. Hereditary History Preserving Bisimilarity Is Undecidable

    DEFF Research Database (Denmark)

    Jurdzinski, Marcin; Nielsen, Mogens

    2000-01-01

    History preserving bisimilarity (hp-bisimilarity) and hereditary history preserving bisimilarity (hhp-bisimilarity) are behavioural equivalences taking into account causal relationships between events of concurrent systems. Their prominent feature is being preserved under action refinement...

  13. Eeyore: a novel mouse model of hereditary deafness.

    Directory of Open Access Journals (Sweden)

    Kerry A Miller

    Full Text Available Animal models that recapitulate human disease are proving to be an invaluable tool in the identification of novel disease-associated genes. These models can improve our understanding of the complex genetic mechanisms involved in disease and provide a basis to guide therapeutic strategies to combat these conditions. We have identified a novel mouse model of non-syndromic sensorineural hearing loss with linkage to a region on chromosome 18. Eeyore mutant mice have early onset progressive hearing impairment and show abnormal structure of the sensory epithelium from as early as 4 weeks of age. Ultrastructural and histological analyses show irregular hair cell structure and degeneration of the sensory hair bundles in the cochlea. The identification of new genes involved in hearing is central to understanding the complex genetic pathways involved in the hearing process and the loci at which these pathways are interrupted in people with a genetic hearing loss. We therefore discuss possible candidate genes within the linkage region identified in eeyore that may underlie the deafness phenotype in these mice. Eeyore provides a new model of hereditary sensorineural deafness and will be an important tool in the search for novel deafness genes.

  14. Induced pluripotent stem cells:Landscape for studying and treating hereditary hearing loss

    Institute of Scientific and Technical Information of China (English)

    Tao Peng; Yunpeng Dong; Ganghua Zhu; Dinghua Xie

    2014-01-01

    Hearing loss (HL) is one of the most widespread sensory disorders, affecting approximately 1 in 500 newborns. Heritable diseases of the inner ear are the leading causes of prelingual HL. Treating of hereditary HL and understanding its underlying mechanisms remain difficult challenges to otolaryngologists. As stem cells are capable of self-renewal and differentiation, they are ideally suited both for disease modeling and regenerative medicine. Recently, description of induced pluripotent stem cells (iPSCs) has allowed the field of disease modeling and personalized therapy to become far more accessible and physiologically relevant, as iPSCs can be generated from patients of any genetic background. This review briefly describes the advantages of iPSCs technology and discusses potential applications of this powerful biological tool in studying and treating hereditary HL.

  15. A Review of Hereditary Fructose Intolerance

    Directory of Open Access Journals (Sweden)

    Mogoş Tiberius

    2016-03-01

    Full Text Available Fructose intolerance is a metabolic disorder with hereditary determinism, clinically manifested on terms of fructose intake. Untreated, hereditary fructose intolerance may result in renal and hepatic failure. Unfortunately, there are no formal diagnostic and surveillance guidelines for this disease. If identified and treated before the occurrence of permanent organ damage, patients can improve their symptoms and self-rated health. Implementation and adherence to a strict fructose free diet is often difficult, but not impossible.

  16. Report sensory analyses veal

    NARCIS (Netherlands)

    Veldman, M.; Schelvis-Smit, A.A.M.

    2005-01-01

    On behalf of a client of Animal Sciences Group, different varieties of veal were analyzed by both instrumental and sensory analyses. The sensory evaluation was performed with a sensory analytical panel in the period of 13th of May and 31st of May, 2005. The three varieties of veal were: young bull,

  17. Hereditary And Acquired Chronic Demyelination Neuropathies : A Clinical, electrophysiological And Histopathological Study

    Directory of Open Access Journals (Sweden)

    Menon A

    1999-01-01

    Full Text Available Differentiating hereditary motor sensory neuropathy (HMSN from chronic inflammatory demyelinating polyneuropathy (CIDP is often difficult especially when the disease starts at an early age and has protracted course. This study compares the clinical, electro, physiological and histopathological features of hereditary and acquired chronic demyelinating neuropathies. Records of 26 patients of chronic demyelinating neuropathy who underwent sural nerve biopsy were reviewed; HMSN 9, CIDP 13, chronic relapsing demyelinating polyneuropathy (CRDP-4, Salient features of the HMSN group were: Consanguineous parentage-4, onset in first decade-9, skeletal markers-7, absence of positive sensory symptoms- 7 and clinically thickened nerves-6. None of the patients with acquired neuropathy had skeletal markers, 11 had positive sensory symptoms and only 4 had nerve thickening. Electrophysiological evaluation in 22 motor nerves in the HMSN group revealed: inexcitable nerves -13, prolonged distal latency - 6, slow conduction velocity-8 and prolonged f wave latency-3. The 44 motor nerves in patients with acquired neuropathy showed: inexcitable nerves- 7, prolonged distal latency-35, slow conduction velocity-34, f wave prolongation-30 and conduction block 9. Elevated CSF protein was noticed only in acquired group (77%. Pathologically in HMSN the fibre loss was always diffuse and onion bulb formation was frequent while endoneural edema and inflammatory infiltration were absent in this group. Selection of patients with chronic demyelinating neuropathies for therapeutic modulation needs comprehensive clinical and laboratory evaluation.

  18. Accessibility and sensory experiences

    DEFF Research Database (Denmark)

    Ryhl, Camilla

    2010-01-01

    This article introduces a new design concept; sensory accessibility. While acknowledging the importance of sensory experiences in architectural quality, as well as the importance of accommodating user needs the concept combines three equally important factors; architecture, the senses and accessi......This article introduces a new design concept; sensory accessibility. While acknowledging the importance of sensory experiences in architectural quality, as well as the importance of accommodating user needs the concept combines three equally important factors; architecture, the senses...... and accessibility. Sensory accessibility accommodates aspects of a sensory disability and describes architectural design requirements needed to ensure access to architectural experiences. In the context of architecture accessibility has become a design concept of its own. It is generally described as ensuring...... physical access to the built environment by accommodating physical disabilities. While the existing concept of accessibility ensures the physical access of everyone to a given space, sensory accessibility ensures the choice of everyone to stay and be able to participate and experience....

  19. Prevalence of autoantibodies in a group of hereditary angioedema patients.

    Science.gov (United States)

    Dortas Junior, Sergio Duarte; Valle, Solange Oliveira Rodrigues; Levy, Soloni Afra Pires; Tortora, Rosangela P; Abe, Augusto Tiaqui; Pires, Gisele Viana; Papi, José Angelo de Souza; França, Alfeu Tavares

    2012-01-01

    Hereditary Angioedema is a dominantly inherited disease. Routine screening of autoantibodies (AAB) is not recommended for individuals with Hereditary Angioedema; however, prevalence of these antibodies in Hereditary Angioedema patients is not well documented. We aim to determine the prevalence of AAB so that individuals at risk of developing autoimmune diseases can be identified. Fifteen patients with Hereditary Angioedema attended at Clementino Fraga Filho University Hospital accepted to participate in this study. Prevalence of AAB was 40%. Our data indicate high prevalence of AAB in patients with Hereditary Angioedema. Large-scale studies should be considered to determine the significance of these AAB in the follow-up care of patients with Hereditary Angioedema.

  20. Hereditary angioedema may not be the only cause of abdominal pain in patients with hereditary angioedema!

    Directory of Open Access Journals (Sweden)

    Ozgur Kartal

    2016-09-01

    Full Text Available Abdominal pain is one of the basic clinical presentations of the hereditary angioedema and danazol is a common medicine which has been used for long years in patients with hereditary angioedema. We present two hereditary angioedema patients with abdominal pain albeit under danazol treatment, whose final diagnoses was colon carcinoma. There are two consequences in this article which shall be insisted on: First; in patients with hereditary angioedema, the differential diagnosis of and ldquo;abdominal pain and rdquo; is always important even though hereditary angioedema diagnosis exists. And the second; It can be hardy speculated that long term danazol treatment may cause different malignancies. [Cukurova Med J 2016; 41(3.000: 567-569

  1. [Genetics of hereditary iron overload].

    Science.gov (United States)

    Le Gall, Jean-Yves; Jouanolle, Anne-Marie; Fergelot, Patricia; Mosser, Jean; David, Véronique

    2004-01-01

    The classification of hereditary abnormalities of iron metabolism was recently expanded and diversified. Genetic hemochromatosis now corresponds to six diseases, namely classical hemochromatosis HFE 1; juvenile hemochromatosis HFE 2 due to mutations in an unidentified gene on chromosome 1; hemochromatosis HFE 3 due to mutations in the transferrin receptor 2 (TfR2); hemochromatosis HFE 4 caused by a mutation in the H subunit of ferritin; and hemochromatosis HFE 6 whose gene is hepcidine (HAMP). Systemic iron overload is also associated with aceruloplasminemia, atransferrinemia and the "Gracile" syndrome caused by mutations in BCS1L. The genes responsible for neonatal and African forms of iron overload are unknown. Other genetic diseases are due to localized iron overload: Friedreich's ataxia results from the expansion of triple nucleotide repeats within the frataxin (FRDA) gene; two forms of X-linked sideroblastic anemia are due to mutations within the delta aminolevulinate synthetase (ALAS 2) or ABC-7 genes; Hallervorden-Spatz syndrome is caused by a pantothenate kinase 2 gene (PANK-2) defect; neuroferritinopathies; and hyperferritinemia--cataract syndrome due to a mutation within the L-ferritin gene. In addition to this wide range of genetic abnormalities, two other features characterize these iron disorders: 1) most are transmitted by an autosomal recessive mechanism, but some, including hemochromatosis type 4, have dominant transmission; and 2) most correspond to cytosolic iron accumulation while some, like Friedreich's ataxia, are disorders of mitochondrial metabolism.

  2. Endocrine dysfunction in hereditary hemochromatosis.

    Science.gov (United States)

    Pelusi, C; Gasparini, D I; Bianchi, N; Pasquali, R

    2016-08-01

    Hereditary hemochromatosis (HH) is a genetic disorder of iron overload and subsequent organ damage. Five types of HH are known, classified by age of onset, genetic cause, clinical manifestations and mode of inheritance. Except for the rare form of juvenile haemochromatosis, symptoms do not usually appear until after decades of progressive iron loading and may be triggered by environmental and lifestyle factors. Despite the last decades discovery of genetic and phenotype diversity of HH, early studies showed a frequent involvement of the endocrine glands where diabetes and hypogonadism are the most common encountered endocrinopathies. The pathogenesis of diabetes is still relatively unclear, but the main mechanisms include the loss of insulin secretory capacity and insulin resistance secondary to liver damage. The presence of obesity and/or genetic predisposition may represent addictive risk factor for the development of this metabolic disease. Although old cases of primary gonad involvement are described, hypogonadism is mainly secondary to selective deposition of iron on the gonadotropin-producing cells of the pituitary gland, leading to hormonal impaired secretion. Cases of hypopituitarism or selected tropin defects, and abnormalities of adrenal, thyroid and parathyroid glands, even if rare, are reported. The prevalence of individual gland dysfunction varies enormously within studies for several bias due to small numbers of and selected cases analyzed, mixed genotypes and missing data on medical history. Moreover, in the last few years early screening and awareness of the disease among physicians have allowed hemochromatosis to be diagnosed in most cases at early stages when patients have no symptoms. Therefore, the clinical presentation of this disease has changed significantly and the recognized common complications are encountered less frequently. This review summarizes the current knowledge on HH-associated endocrinopathies.

  3. Late onset hereditary episodic ataxia.

    Science.gov (United States)

    Damak, M; Riant, F; Boukobza, M; Tournier-Lasserve, E; Bousser, M-G; Vahedi, K

    2009-05-01

    Episodic ataxias (EA) are hereditary paroxysmal neurological diseases with considerable clinical and genetic heterogeneity. So far seven loci have been reported and four different genes have been identified. Analysis of additional sporadic or familial cases is needed to better delineate the clinical and genetic spectrum of EA. A two generation French family with late onset episodic ataxia was examined. All consenting family members had a brain MRI with volumetric analysis of the cerebellum. Haplotype analysis was performed for the EA2 locus (19p13), the EA5 locus (2q22), the EA6 locus (5p13) and the EA7 locus (19q13). Mutation screening was performed for all exons of CACNA1A (EA2), EAAT1 (EA6) and the coding sequence of KCNA1 (EA1). Four family members had episodic ataxia with onset between 48 and 56 years of age but with heterogeneity in the severity and duration of symptoms. The two most severely affected had daily attacks of EA with a slowly progressive and disabling permanent cerebellar ataxia and a poor response to acetazolamide. Brain MRI showed in three affected members a decrease in the ratio of cerebellar volume:total intracranial volume, indicating cerebellar atrophy. No deleterious mutation was found in CACNA1A, SCA6, EAAT1 or KCNA1. In addition, the EA5 locus was excluded. A new phenotype of episodic ataxia has been described, characterised clinically by a late onset and progressive permanent cerebellar signs, and genetically by exclusion of the genes so far identified in EA.

  4. [Peripheral sensory neuropathy produced by a megadose of vitamin B6].

    Science.gov (United States)

    Ohnishi, A; Ishibashi, H; Ohtani, K; Matsunaga, K; Yamamoto, T

    1985-06-01

    Clinical cases of sensory neuropathy produced by a megadose of vitamin B6 have been reported in English literatures. We investigated the ordinary daily dosage and maximal dose of vitamin B6 widely adopted in Japan, and the amount of vitamin B6 per unit (per tablet, capsule or ampule) available in our medical practice. We concluded that in Japan it is very rare to administer such a large dose of vitamin B6 that produced sensory neuropathy described in the literatures. In our experimental study, Sprague-Dawley rats were intraperitoneally given a total amount of 14,000 mg/kg of body weight of pyridoxine hydrochloride in ten separate doses. They developed an ataxic gait. The occurrence of the degeneration of nerve cell bodies and peripheral axons of lumbar primary sensory neurons were histologically demonstrated. Although in Japan no clinical cases of neuropathy produced by a megadose of vitamin B6 have been reported to our knowledge, it is necessary to be aware of the possible occurrence of such neuropathy among patients with polyneuropathy of unknown etiology or who have been receiving vitamin B6 for a long time.

  5. Genetic profiles distinguish different types of hereditary ovarian cancer

    DEFF Research Database (Denmark)

    Domanska, Katarina; Malander, Susanne; Staaf, Johan

    2010-01-01

    Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian canc...... that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer....

  6. Pancreatic cancer risk in hereditary pancreatitis

    Directory of Open Access Journals (Sweden)

    Frank Ulrich Weiss

    2014-02-01

    Full Text Available Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1 gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. Hereditary pancreatitis often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of hereditary pancreatitis patients to develop pancreatic cancer.

  7. Hereditary cerebral small vessel disease and stroke

    DEFF Research Database (Denmark)

    Søndergaard, Christian Baastrup; Nielsen, Jørgen Erik; Hansen, Christine Krarup

    2017-01-01

    of this systematic review is to provide a guide for determining when to consider molecular genetic testing in patients presenting with small vessel disease and stroke. CADASIL, CARASIL, collagen type IV mutations (including PADMAL), retinal vasculopathy with cerebral leukodystrophy, Fabry disease, hereditary...... cerebral hemorrhage with amyloidosis, and forkhead box C1 mutations are described in terms of genetics, pathology, clinical manifestation, imaging, and diagnosis. These monogenic disorders are often characterized by early-age stroke, but also by migraine, mood disturbances, vascular dementia and often gait......Cerebral small vessel disease is considered hereditary in about 5% of patients and is characterized by lacunar infarcts and white matter hyperintensities on MRI. Several monogenic hereditary diseases causing cerebral small vessel disease and stroke have been identified. The purpose...

  8. High liver glycogen in hereditary fructose intolerance.

    Science.gov (United States)

    Cain, A R; Ryman, B E

    1971-11-01

    A case of hereditary fructose intolerance is reported in a girl aged 2 years at the time of her death. She had apparently progressed normally until the age of 14 months. At 19 months she was admitted to hospital with failure to thrive, hepatomegaly, and superficial infections. Investigations revealed hypoglycaemia, persistent acidosis, aminoaciduria, and a high liver glycogen level which suggested that she had glycogen storage disease. There was also some evidence of malabsorption. At necropsy the liver enzyme estimations showed that fructose 1-phosphate aldolase activity was absent and that fructose 1,6-diphosphate aldolase activity was reduced. Hereditary fructose intolerance and glycogen storage disease have been confused in the past on clinical grounds, but a high liver glycogen level has not previously been reported in hereditary fructose intolerance.

  9. Hereditary Cerebellar Ataxias: A Korean Perspective

    Directory of Open Access Journals (Sweden)

    Ji Sun Kim

    2015-05-01

    Full Text Available Hereditary ataxia is a heterogeneous disorder characterized by progressive ataxia combined with/without peripheral neuropathy, extrapyramidal symptoms, pyramidal symptoms, seizure, and multiple systematic involvements. More than 35 autosomal dominant cerebellar ataxias have been designated as spinocerebellar ataxia, and there are 55 recessive ataxias that have not been named systematically. Conducting genetic sequencing to confirm a diagnosis is difficult due to the large amount of subtypes with phenotypic overlap. The prevalence of hereditary ataxia can vary among countries, and estimations of prevalence and subtype frequencies are necessary for planning a diagnostic strategy in a specific population. This review covers the various hereditary ataxias reported in the Korean population with a focus on the prevalence and subtype frequencies as the clinical characteristics of the various subtypes.

  10. [Hereditary optic neuropathies: clinical and molecular genetic characteristics].

    Science.gov (United States)

    Khanakova, N A; Sheremet, N L; Loginova, A N; Chukhrova, A L; Poliakov, A V

    2013-01-01

    The article presents a review of literature on hereditary optic neuropathies: Leber mitochondrial hereditary optic neuropathy, autosomal dominant and autosomal recessive optic neuropathies, X-linked optic atrophy. Clinical and molecular genetic characteristics are covered. Isolated optic neuropathies, as well as hereditary optic disorders, being a part of a complex syndromic disease are described.

  11. Extramedullary paraspinal hematopoiesis in hereditary spherocytosis

    Directory of Open Access Journals (Sweden)

    Gogia P

    2008-01-01

    Full Text Available Hereditary spherocytosis (HS is a common inherited hemolytic anemia due to red cell membrane defects. Extramedullary hematopoiesis is a compensatory response to insufficient bone marrow blood cell production. The preferred sites of extramedullary hematopoietic involvement are the spleen, liver and lymph nodes; but in HS, the posterior paravertebral mediastinum is also commonly involved. We report a case of a 50-year-old male who presented to us in respiratory distress and with bilateral paravertebral posterior mediastinal masses, which on trucut biopsy were found to be extra-hematopoietic masses; and the patient was found to have hereditary spherocytosis.

  12. Disease expression in women with hereditary angioedema

    DEFF Research Database (Denmark)

    Bouillet, Laurence; Longhurst, Hilary; Boccon-Gibod, Isabelle

    2008-01-01

    project launched by the European Union, data on 150 postpubertal women with hereditary angioedema were collected in 8 countries, using a patient-based questionnaire. RESULTS: Puberty worsened the disease for 62%. Combined oral contraceptives worsened the disease for 79%, whereas progestogen-only pills......OBJECTIVE: Fluctuations in sex hormones can trigger angioedema attacks in women with hereditary angioedema. Combined oral contraceptive therapies, as well as pregnancy, can induce severe attacks. The course of angioedema may be very variable in different women. STUDY DESIGN: Within the PREHAEAT...

  13. Hereditary angioedema with normal C1 inhibitor.

    Science.gov (United States)

    Bork, Konrad

    2013-11-01

    Until recently it was assumed that hereditary angioedema was a disease that results exclusively from a genetic deficiency of the C1 inhibitor. In 2000, families with hereditary angioedema, normal C1 inhibitor activity, and protein in plasma were described. Since then, numerous patients and families with that condition have been reported. Most of the patients were women. In many of the affected women, oral contraceptives, hormone replacement therapy containing estrogens, and pregnancies triggered the clinical symptoms. In some families mutations in the coagulation factor XII (Hageman factor) gene were detected.

  14. Diagnosis and management of hereditary hemochromatosis.

    Science.gov (United States)

    Salgia, Reena J; Brown, Kimberly

    2015-02-01

    Hereditary hemochromatosis is a rare genetic disorder that can have significant clinical consequences. Hemochromatosis is associated with iron overload, and can initially be recognized through laboratory testing for serum ferritin and transferrin saturation. Genetic testing for the HFE mutation can be performed in patients with elevated iron indices and a suspicion for hemochromatosis or liver disease. The main pathway resulting in iron overload is through altered hepcidin levels. Treatment of patients with the clinical phenotype of hereditary hemochromatosis is commonly through phlebotomy for removal of excess iron stores. This article highlights the current information and data regarding the diagnosis and management of hemochromatosis.

  15. Albright hereditary osteodystrophy: A rare case report

    Directory of Open Access Journals (Sweden)

    Goswami M

    2009-09-01

    Full Text Available Albright hereditary osteodystrophy (AHO is a rare hereditary metabolic disorder that may be associated with or without resistant to parathyroid hormone (pseudohypoparathyroidism. It is commonly characterized by a constellation of physical features of short stature, round face, short neck, and small metacarpals and metatarsals, mild mental retardation, osteoporosis, subcutaneous calcification, and sometimes olfactory and hearing functional defect. Hypocalcaemia and hyperphosphatemia are the most important manifestations of the case. We report a clinical case of siblings with AHO with reduced Gs-alpha activity and we discuss their clinical features with oral manifestations, radiographic findings, laboratory tests along with treatment.

  16. Mutation analysis of genes within the dynactin complex in a cohort of hereditary peripheral neuropathies.

    Science.gov (United States)

    Tey, S; Ahmad-Annuar, A; Drew, A P; Shahrizaila, N; Nicholson, G A; Kennerson, M L

    2016-08-01

    The cytoplasmic dynein-dynactin genes are attractive candidates for neurodegenerative disorders given their functional role in retrograde transport along neurons. The cytoplasmic dynein heavy chain (DYNC1H1) gene has been implicated in various neurodegenerative disorders, and dynactin 1 (DCTN1) genes have been implicated in a wide spectrum of disorders including motor neuron disease, Parkinson's disease, spinobulbar muscular atrophy and hereditary spastic paraplegia. However, the involvement of other dynactin genes with inherited peripheral neuropathies (IPN) namely, hereditary sensory neuropathy, hereditary motor neuropathy and Charcot-Marie-Tooth disease is under reported. We screened eight genes; DCTN1-6 and ACTR1A and ACTR1B in 136 IPN patients using whole-exome sequencing and high-resolution melt (HRM) analysis. Eight non-synonymous variants (including one novel variant) and three synonymous variants were identified. Four variants have been reported previously in other studies, however segregation analysis within family members excluded them from causing IPN in these families. No variants of disease significance were identified in this study suggesting the dynactin genes are unlikely to be a common cause of IPNs. However, with the ease of querying gene variants from exome data, these genes remain worthwhile candidates to assess unsolved IPN families for variants that may affect the function of the proteins.

  17. Autosomal recessive hereditary auditory neuropathy

    Institute of Scientific and Technical Information of China (English)

    王秋菊; 顾瑞; 曹菊阳

    2003-01-01

    evidence of peripheral neuropathy at the time of this writing. Conclusions: In this study, patients with feature of non- syndromic hereditary auditory neuropathy were identified in three Chinese families.Pedigree analysis indicates autosomal recessive inheritances in the pedigrees. The observed inheritance and clinical audiologic findings are different from those previously described for non-syndromic low-frequency sensorineural hearing loss. This information should facilitate future molecular candidate genes screening for understanding the mechanism of AN.

  18. HIV Associated Sensory Neuropathy

    OpenAIRE

    G, Amruth; S, Praveen-kumar; B, Nataraju; BS, Nagaraja

    2014-01-01

    Background: In the era of highly active antiretroviral therapy, sensory neuropathies have increased in prevalence. We have documented the frequency and profile of the two most common forms of sensory neuropathies associated with Human Immunodeficiency Virus (HIV) infection and looked into clinicoelectrophysiological correlates to differentiate the two entities.

  19. UNCOMMON SENSORY METHODOLOGIES

    Directory of Open Access Journals (Sweden)

    Vladimír Vietoris

    2015-02-01

    Full Text Available Sensory science is the young but the rapidly developing field of the food industry. Actually, the great emphasis is given to the production of rapid techniques of data collection, the difference between consumers and trained panel is obscured and the role of sensory methodologists is to prepare the ways for evaluation, by which a lay panel (consumers can achieve identical results as a trained panel. Currently, there are several conventional methods of sensory evaluation of food (ISO standards, but more sensory laboratories are developing methodologies that are not strict enough in the selection of evaluators, their mechanism is easily understandable and the results are easily interpretable. This paper deals with mapping of marginal methods used in sensory evaluation of food (new types of profiles, CATA, TDS, napping.

  20. Secondary chondrosarcoma: Malignant transformation of pre-existing hereditary and non-hereditary cartilaginous lesions

    Directory of Open Access Journals (Sweden)

    Susanna C.S. Vlok

    2014-12-01

    Full Text Available Secondary chondrosarcoma is a malignant hyaline cartilage tumour originating from a cartilaginous precursor, either osteochondroma or enchondroma. We contrast two different cases of biopsy-proven secondary chondrosarcomas resulting from benign, pre-existing cartilaginous lesions – our aim is to contrast and compare these two benign conditions consisting of multiple cartilaginous lesions – one hereditary and the other non-hereditary – and emphasise their potential for malignant transformation.

  1. Hereditary spherocytosis: Consequences of delayed diagnosis

    Directory of Open Access Journals (Sweden)

    Sarah C Steward

    2014-08-01

    Full Text Available Objective: To determine whether patients with undiagnosed hereditary spherocytosis hospitalized for transfusions might have avoided hospitalization via earlier diagnosis. Study design: Charts of all (N = 30 patients with hereditary spherocytosis seen in pediatric hematology at West Virginia University-Charleston were reviewed. Family and transfusion history and presence of neonatal jaundice were recorded. Complete blood count and reticulocyte values during infancy were available for 20 of 30 patients, while baseline steady-state values were available for all 30. Results: Transfusions were given to 22 patients; 12 of 14 with an aplastic crisis were undiagnosed. In 10 of 12, the severity of anemia led to hospitalization (3 to intensive care. All 10 had prior mean corpuscular hemoglobin concentration and/or red cell distribution width elevations and a history of neonatal jaundice; 7 of 10 had a positive family history. Conclusions: Undiagnosed hereditary spherocytosis may lead to inpatient transfusions for severe anemia. Earlier detection of hereditary spherocytosis is easily achievable and may reduce hospitalizations via closer monitoring.

  2. Gynecologic screening in hereditary nonpolyposis colorectal cancer

    NARCIS (Netherlands)

    Rijcken, FEM; Mourits, MJE; Kleibeuker, JH; Hollema, H; van der Zee, AGJ

    2003-01-01

    Objective. In hereditary nonpolyposis colorectal cancer (HNPCC), women with a mismatch repair (MMR) gene mutation have a cumulative lifetime risk of 25-50% for endometrial cancer and 8-12% for ovarian cancer. Therefore, female members of HNPCC families are offered an annual gynecologic and transvagi

  3. Hereditary periodic fever and reactive amyloidosis.

    NARCIS (Netherlands)

    Hilst, J.C.H. van der; Simon, A.; Drenth, J.P.H.

    2005-01-01

    Hereditary periodic fever syndromes (HPF) are a group of diseases characterised by recurrences of fever and inflammation separated by symptom-free intervals. Familial Mediterranean fever (FMF) is the most frequent entity within this group of disorders which further consists of

  4. Hereditary spherocytosis presenting as indolent leg ulcers

    Directory of Open Access Journals (Sweden)

    Muhammed K

    1997-01-01

    Full Text Available Indolent leg ulcertation, which is the rarest manifestation of hereditary spherocytosis, started at the age of 5 years affecting a 15-year-old boy and his mother is reported. Review of literature showed very few reports from India and abroad. The response to oral folic acid was excellent

  5. [Sudden blindness: consider Leber's hereditary optic neuropathy

    NARCIS (Netherlands)

    Schieving, J.H.; Vries, L.B.A. de; Hol, F.A.; Stroink, H.

    2008-01-01

    In 3 young male patients, aged 10, 19 and 21 years respectively, sequential, severe, painless bilateral visual loss occurred. Ophthalmological examination revealed no other abnormalities and this delayed the diagnosis Leber's hereditary optic neuropathy (LHON). LHON is a mitochondrial genetic diseas

  6. Demyelinating polyneuropathy in Leber hereditary optic neuropathy.

    NARCIS (Netherlands)

    Gilhuis, H.J.; Schelhaas, H.J.; Cruysberg, J.R.M.; Zwarts, M.J.

    2006-01-01

    We report a patient with Leber hereditary optic neuropathy (G11778A mtDNA) and a severe demyelinating neuropathy, for which no other cause except his mitochondrial disorder could be found. The involvement of the peripheral nervous system of patients with LHON, in particular with a 11778 mtDNA, is di

  7. Major and minor form of hereditary hyperekplexia

    NARCIS (Netherlands)

    Tijssen, MAJ; Vergouwe, MN; van Dijk, JG; Rees, M; Frants, RR; Brown, P

    2002-01-01

    Hyperekplexia is a hereditary neurological disorder characterized by excessive startle responses. Within the disorder two clinical forms can be distinguished. The major form is characterized by continuous generalized stiffness in the first year of life and an exaggerated startle reflex, accompanied

  8. Clinical management of hereditary colorectal cancer syndromes.

    Science.gov (United States)

    Vasen, Hans F A; Tomlinson, Ian; Castells, Antoni

    2015-02-01

    Hereditary factors are involved in the development of a substantial proportion of all cases of colorectal cancer. Inherited forms of colorectal cancer are usually subdivided into polyposis syndromes characterized by the development of multiple colorectal polyps and nonpolyposis syndromes characterized by the development of few or no polyps. Timely identification of hereditary colorectal cancer syndromes is vital because patient participation in early detection programmes prevents premature death due to cancer. Polyposis syndromes are fairly easy to recognize, but some patients might have characteristics that overlap with other clinically defined syndromes. Comprehensive analysis of the genes known to be associated with polyposis syndromes helps to establish the final diagnosis in these patients. Recognizing Lynch syndrome is more difficult than other polyposis syndromes owing to the absence of pathognomonic features. Most investigators therefore recommend performing systematic molecular analysis of all newly diagnosed colorectal cancer using immunohistochemical methods. The implementation in clinical practice of new high-throughput methods for molecular analysis might further increase the identification of individuals at risk of hereditary colorectal cancer. This Review describes the clinical management of the various hereditary colorectal cancer syndromes and demonstrates the advantage of using a classification based on the underlying gene defects.

  9. Epidemiology of Non-hereditary Angioedema

    DEFF Research Database (Denmark)

    Madsen, Flemming; Attermann, Jorn; Linneberg, Allan

    2012-01-01

    % in the abdominal area, 17% had diarrhoea, 11% had vomiting and 6% fainted during attacks. Non-hereditary angioedema has high lifetime prevalence and becomes chronic in approximately 50% of affected patients. Symptoms in the larynx and throat, as well as non-specific symptoms, such as dizziness and abdominal pain...

  10. Reprogramming development of experimental hereditary hypertension

    NARCIS (Netherlands)

    Koeners, M.P.M.

    2007-01-01

    The aim of the studies described in this thesis was to investigate the development of experimental hereditary hypertension and to persistently ameliorate the development of hypertension due brief interventions during early development (perinatal treatment). We used two different models of experiment

  11. Genetic spectrum of hereditary neuropathies with onset in the first year of life.

    Science.gov (United States)

    Baets, Jonathan; Deconinck, Tine; De Vriendt, Els; Zimoń, Magdalena; Yperzeele, Laetitia; Van Hoorenbeeck, Kim; Peeters, Kristien; Spiegel, Ronen; Parman, Yesim; Ceulemans, Berten; Van Bogaert, Patrick; Pou-Serradell, Adolf; Bernert, Günther; Dinopoulos, Argirios; Auer-Grumbach, Michaela; Sallinen, Satu-Leena; Fabrizi, Gian Maria; Pauly, Fernand; Van den Bergh, Peter; Bilir, Birdal; Battaloglu, Esra; Madrid, Ricardo E; Kabzińska, Dagmara; Kochanski, Andrzej; Topaloglu, Haluk; Miller, Geoffrey; Jordanova, Albena; Timmerman, Vincent; De Jonghe, Peter

    2011-09-01

    Early onset hereditary motor and sensory neuropathies are rare disorders encompassing congenital hypomyelinating neuropathy with disease onset in the direct post-natal period and Dejerine-Sottas neuropathy starting in infancy. The clinical spectrum, however, reaches beyond the boundaries of these two historically defined disease entities. De novo dominant mutations in PMP22, MPZ and EGR2 are known to be a typical cause of very early onset hereditary neuropathies. In addition, mutations in several other dominant and recessive genes for Charcot-Marie-Tooth disease may lead to similar phenotypes. To estimate mutation frequencies and to gain detailed insights into the genetic and phenotypic heterogeneity of early onset hereditary neuropathies, we selected a heterogeneous cohort of 77 unrelated patients who presented with symptoms of peripheral neuropathy within the first year of life. The majority of these patients were isolated in their family. We performed systematic mutation screening by means of direct sequencing of the coding regions of 11 genes: MFN2, PMP22, MPZ, EGR2, GDAP1, NEFL, FGD4, MTMR2, PRX, SBF2 and SH3TC2. In addition, screening for the Charcot-Marie-Tooth type 1A duplication on chromosome 17p11.2-12 was performed. In 35 patients (45%), mutations were identified. Mutations in MPZ, PMP22 and EGR2 were found most frequently in patients presenting with early hypotonia and breathing difficulties. The recessive genes FGD4, PRX, MTMR2, SBF2, SH3TC2 and GDAP1 were mutated in patients presenting with early foot deformities and variable delay in motor milestones after an uneventful neonatal period. Several patients displaying congenital foot deformities but an otherwise normal early development carried the Charcot-Marie-Tooth type 1A duplication. This study clearly illustrates the genetic heterogeneity underlying hereditary neuropathies with infantile onset.

  12. [Sensory and autonomic neuropathies and pain-related channelopathies].

    Science.gov (United States)

    Kurth, I

    2015-08-01

    Loss of pain perception can result from neurodevelopmental defects, degeneration of nociceptive fibers, or altered excitability of sensory neurons. Hereditary neurodegeneration leading to pain loss is classified as sensory and autonomic neuropathy (HSAN). Mutations in approximately 15 genes have been identified in the group of HSAN disorders. Hallmark of the disease is a liability to injury because of impaired acute pain as a warning system to prevent harm. The clinically overlapping "congenital insensitivity to pain (CIP)" is caused by mutations in voltage-gated sodium channels, which control the excitability of nociceptors. However, mutations in the latter genes can also result in disorders with increased pain susceptibility. This review summarizes the clinical presentation of HSAN and pain-related channelopathies and discusses the underlying disease mechanisms.

  13. Cate's Story: Hereditary Diffuse Gastric Cancer.

    Science.gov (United States)

    Rogers, Megan

    2016-08-01

    Gastric cancer is a major cause of cancer-related mortality worldwide and is thought to be responsible for about 10% of cancer-related deaths across the globe. A small proportion of all gastric cancers arise because of a known hereditary syndrome, the most common of which is hereditary diffuse gastric cancer (HDGC). This is an autosomal dominant genetic disease characterized by an increased risk of developing diffuse gastric cancer at a young age. The gene responsible for HDGC is CDH1, also known as E-cadherin, a germline mutation conferring an 80% risk of developing gastric cancer during the lifetime of the carrier. Females with germline CDH1 mutations face an additional risk of developing lobular breast cancer, with a reported cumulative risk of 60% by the age of 80 years.
.

  14. Hereditary diffuse gastric cancer--An overview.

    Science.gov (United States)

    Gurzu, Simona; Jung, Ioan; Orlowska, Janina; Sugimura, Haruhiko; Kadar, Zoltan; Turdean, Sabin; Bara, Tivadar

    2015-09-01

    The incidence of gastric cancer varies by up to ten fold throughout the world, and the geographic distribution of hereditary cases is not well explored. Familial clustering is seen in 10% of cases, and approximately 3% of all gastric cancers develop due to hereditary diffuse gastric cancer (HDGC). In this review, the characteristics of HDGC are presented according to molecular particularities, geographic distribution, and other parameters. Based on our experience and the data from the literature, we discuss the possibility of applying a mutation signature (spectrum) study and adductomic approaches to a comparative carcinogenesis of HDGC. We also provide a comprehensive, up-to-date review of genetic counseling and criteria for screening and surveillance of eligible families.

  15. Hereditary angioedema type I: a case report.

    Science.gov (United States)

    Muñoz Peralta, Francisca; Buller Vigueira, Eva; Cabello Pulido, Juana

    2016-01-28

    Hereditary angioedema is a rare disease with great heterogeneity of symptoms such as edema of the skin, gastro-intestinal mucosa and larynx or pharynx. Even though there are three types, the most frequent is type I, which is a result from a deficiency of the complement C1 inhibitor. The severity of its symptoms along with the low prevalence of the disease and the need for appropriate specific treatment make the diagnosis and treatment of the pathology an outstanding subject for the family physician. The present is the case of a male teenager with alpha-1 antitrypsin deficiency since he was six months old, angioedema on arms and legs since 11 years old and diagnosed with hereditary angioedema type I one year after. The definitive diagnosis of the disease enabled an appropriate treatment which consists in preventing outbreaks that may compromise the patient's life and, if they occur, administration of complement C1 inhibitor.

  16. Hereditary spastic paraplegia with cerebellar ataxia

    DEFF Research Database (Denmark)

    Nielsen, J E; Johnsen, B; Koefoed, P

    2004-01-01

    Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria...... in those individuals who were clinically affected by a complex phenotype consisting of HSP and cerebellar ataxia. Other features noted in this kindred including epilepsy, cognitive impairment, depression, and migraine did not segregate with the HSP phenotype or mutation, and therefore the significance...... relatively decreased regional cerebral blood flow in most of the cerebellum. We conclude that this kindred demonstrates a considerable overlap between cerebellar ataxia and spastic paraplegia, emphasizing the marked clinical heterogeneity of HSP associated with spastin mutations....

  17. The biochemical basis of hereditary fructose intolerance.

    Science.gov (United States)

    Bouteldja, Nadia; Timson, David J

    2010-04-01

    Hereditary fructose intolerance is a rare, but potentially lethal, inherited disorder of fructose metabolism, caused by mutation of the aldolase B gene. Treatment currently relies solely on dietary restriction of problematic sugars. Biochemical study of defective aldolase B enzymes is key to revealing the molecular basis of the disease and providing a stronger basis for improved treatment and diagnosis. Such studies have revealed changes in enzyme activity, stability and oligomerisation. However, linking these changes to disease phenotypes has not always been straightforward. This review gives a general overview of the features of hereditary fructose intolerance, then concentrates on the biochemistry of the AP variant (Ala149Pro variant of aldolase B) and molecular pathological consequences of mutation of the aldolase B gene.

  18. Distal renal tubular acidosis with hereditary spherocytosis.

    Science.gov (United States)

    Sinha, Rajiv; Agarwal, Indira; Bawazir, Waleed M; Bruce, Lesley J

    2013-07-01

    Hereditary spherocytosis (HS) and distal renal tubular acidosis (dRTA), although distinct entities, share the same protein i.e. the anion exchanger1 (AE1) protein. Despite this, their coexistence has been rarely reported. We hereby describe the largest family to date with co-existence of dRTA and HS and discuss the molecular basis for the co-inheritance of these conditions.

  19. Hereditary angioedema:44 years of diagnostic delay

    OpenAIRE

    Peterson, M.P.; Bygum, A

    2016-01-01

    We report a 64-year-old man who suffered from recurrent visible swelling attacks since the age of 20 as well as episodes with severe upper airway edema, resulting in 4 emergency tracheotomies. Eventually after 44 years he was diagnosed with hereditary angioedema (HAE) type II. The aims of this report is to emphasize the importance of awareness concerning HAE, which does not respond to traditional anti-allergic therapy, and remind physicians to test for functional C1-INH deficiency.

  20. Hereditary chin tremor in Parkinson's disease.

    Science.gov (United States)

    Erer, Sevda; Jankovic, Joseph

    2007-11-01

    Hereditary chin tremor (HCT) is characterized by rhythmical, involuntary movements of the chin muscles usually inherited in an autosomal dominant pattern. We describe a 74-year old man with familial, childhood-onset chin tremor, and a 3-year history of progressive hand tremor, gait difficulty, and other parkinsonian features. Since chin tremor often occurs in Parkinson's disease (PD), a coexistent HCT may not be recognized unless past and family history of tremor is carefully explored.

  1. Hereditary Transthyretin Amyloidosis in Eight Chinese Families

    Institute of Scientific and Technical Information of China (English)

    Ling-Chao Meng; He Lyu; Wei Zhang; Jing Liu; Zhao-Xia Wang; Yun Yuan

    2015-01-01

    Background:Mutations of transthyretin (TTR) cause the most common type of autosomal-dominant hereditary systemic amyloidosis,which occurs worldwide.To date,more and more mutations in the TTR gene have been reported.Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family.The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis.Methods:Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014.Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients,for light and electron microscopy examination.The TTR genes from the nine patients were analyzed.Results:The onset age varied from 23 to 68 years.The main manifestations were paresthesia,proximal and/or distal weakness,autonomic dysfunction,cardiomyopathy,vitreous opacity,hearing loss,and glossohypertrophia.Nerve biopsy demonstrated severe loss ofmyelinated fibers in seven cases and amyloid deposits in three.One patient had skin amyloid deposits which were revealed from electron microscopic examination.Genetic analysis showed six kinds of mutations of TTR gene,including Val30Met,Phe33Leu,Ala36Pro,Val30Ala,Phe33Val,and Glu42Gly in exon 2.Conclusions:Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients,the screening for TTR mutations should be performed in all the adult patients,who are clinically suspected with hereditary TTR amyloidosis.

  2. Leber hereditary optic neuropathy mimicking neuromyelitis optica.

    Science.gov (United States)

    McClelland, Collin M; Van Stavern, Gregory P; Tselis, Alex C

    2011-09-01

    Leber hereditary optic neuropathy (LHON) is rarely associated with multiple sclerosis-like features. We present a case of a 65-year-old African American woman with LHON masquerading as neuromyelitis optica (NMO). We highlight the features of the clinical examination and MRI that were suggestive of an alternative diagnosis and review the literature regarding LHON and multiple sclerosis. The diagnosis of LHON should be considered in all cases of acute or subacute bilateral optic neuropathy, including presumed seronegative NMO.

  3. Pitch discrimination in cerebellar patients: evidence for a sensory deficit.

    Science.gov (United States)

    Parsons, Lawrence M; Petacchi, Augusto; Schmahmann, Jeremy D; Bower, James M

    2009-12-15

    In the last two decades, a growing body of research showing cerebellar involvement in an increasing number of nonmotor tasks and systems has prompted an expansion of speculations concerning the function of the cerebellum. Here, we tested the predictions of a hypothesis positing cerebellar involvement in sensory data acquisition. Specifically, we examined the effect of global cerebellar degeneration on primary auditory sensory function by means of a pitch discrimination task. The just noticeable difference in pitch between two tones was measured in 15 healthy controls and in 15 high functioning patients afflicted with varying degrees of global cerebellar degeneration caused by hereditary, idiopathic, paraneoplastic, or postinfectious pancerebellitis. Participants also performed an auditory detection task assessing sustained attention, a test of verbal auditory working memory, and an audiometric test. Patient pitch discrimination thresholds were on average five and a half times those of controls and were proportional to the degree of cerebellar ataxia assessed independently. Patients and controls showed normal hearing thresholds and similar performance in control tasks in sustained attention and verbal auditory working memory. These results suggest there is an effect of cerebellar degeneration on primary auditory function. The findings are consistent with other recent demonstrations of cerebellar-related sensory impairments, and with robust cerebellar auditorily evoked activity, confirmed by quantitative meta-analysis, across a range of functional neuroimaging studies dissociated from attention, motor, affective, and cognitive variables. The data are interpreted in the context of a sensory hypothesis of cerebellar function.

  4. Medical management of hereditary optic neuropathies

    Directory of Open Access Journals (Sweden)

    Chiara eLa Morgia

    2014-07-01

    Full Text Available Hereditary optic neuropathies are diseases of the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e. the maternally inherited Leber’s Hereditary Optic Neuropathy (LHON and Dominant Optic Atrophy (DOA. They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1 and 14484/ND6 for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone. Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising venue that still needs to be validated.

  5. Medical Management of Hereditary Optic Neuropathies

    Science.gov (United States)

    La Morgia, Chiara; Carbonelli, Michele; Barboni, Piero; Sadun, Alfredo Arrigo; Carelli, Valerio

    2014-01-01

    Hereditary optic neuropathies are diseases affecting the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e., the maternally inherited Leber’s hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA). They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is characterized by an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1, and 14484/ND6) for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are still limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone). Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising avenue that still needs to be validated. PMID:25132831

  6. Medical management of hereditary optic neuropathies.

    Science.gov (United States)

    La Morgia, Chiara; Carbonelli, Michele; Barboni, Piero; Sadun, Alfredo Arrigo; Carelli, Valerio

    2014-01-01

    Hereditary optic neuropathies are diseases affecting the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e., the maternally inherited Leber's hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA). They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is characterized by an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1, and 14484/ND6) for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are still limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone). Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising avenue that still needs to be validated.

  7. Brazilian guidelines for the diagnosis and treatment of hereditary angioedema

    OpenAIRE

    Pedro Giavina-Bianchi; Alfeu T. França; GRUMACH, Anete S.; Abílio A Motta; Fátima R Fernandes; Regis A. Campos; Solange O Valle; Rosário, Nelson A.; Dirceu Sole

    2011-01-01

    Hereditary angioedema is an autosomal dominant disease characterized by edema attacks with multiple organ involvement. It is caused by a quantitative or functional deficiency of the C1 inhibitor, which is a member of the serine protease inhibitor family. Hereditary angioedema is unknown to many health professionals and is therefore an underdiagnosed disease. The causes of death from hereditary angioedema include laryngeal edema with asphyxia. The estimated mortality rate in patients in whom t...

  8. Non responsive celiac disease due to coexisting hereditary fructose intolerance.

    Science.gov (United States)

    Bharadia, Lalit; Shivpuri, Deepak

    2012-04-01

    Celiac disease is associated with several genetic disorders, but its association with hereditary fructose intolerance is rare. Hereditary fructose intolerance is a rare autosomal recessive disease of fructose metabolism presenting as vomiting after intake of fructose. An association between these two distinct genetic gastrointestinal disorders is important as treatment failure of celiac disease calls for careful evaluation for hereditary fructose intolerance. We report a patient with an association of these two disorders.

  9. Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis.

    Science.gov (United States)

    Banerji, Aleena; Busse, Paula; Shennak, Mustafa; Lumry, William; Davis-Lorton, Mark; Wedner, Henry J; Jacobs, Joshua; Baker, James; Bernstein, Jonathan A; Lockey, Richard; Li, H Henry; Craig, Timothy; Cicardi, Marco; Riedl, Marc; Al-Ghazawi, Ahmad; Soo, Carolyn; Iarrobino, Ryan; Sexton, Daniel J; TenHoor, Christopher; Kenniston, Jon A; Faucette, Ryan; Still, J Gordon; Kushner, Harvey; Mensah, Robert; Stevens, Chris; Biedenkapp, Joseph C; Chyung, Yung; Adelman, Burt

    2017-02-23

    Background Hereditary angioedema with C1 inhibitor deficiency is characterized by recurrent, unpredictable swelling episodes caused by uncontrolled plasma kallikrein generation and excessive bradykinin release resulting from cleavage of high-molecular-weight kininogen. Lanadelumab (DX-2930) is a new kallikrein inhibitor with the potential for prophylactic treatment of hereditary angioedema with C1 inhibitor deficiency. Methods We conducted a phase 1b, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial. Patients with hereditary angioedema with C1 inhibitor deficiency were randomly assigned in a 2:1 ratio to receive either lanadelumab (24 patients) or placebo (13 patients), in two administrations 14 days apart. Patients assigned to lanadelumab were enrolled in sequential dose groups: total dose of 30 mg (4 patients), 100 mg (4 patients), 300 mg (5 patients), or 400 mg (11 patients). The pharmacodynamic profile of lanadelumab was assessed by measurement of plasma levels of cleaved high-molecular-weight kininogen, and efficacy was assessed by the rate of attacks of angioedema during a prespecified period (day 8 to day 50) in the 300-mg and 400-mg groups as compared with the placebo group. Results No discontinuations occurred because of adverse events, serious adverse events, or deaths in patients who received lanadelumab. The most common adverse events that emerged during treatment were attacks of angioedema, injection-site pain, and headache. Dose-proportional increases in serum concentrations of lanadelumab were observed; the mean elimination half-life was approximately 2 weeks. Lanadelumab at a dose of 300 mg or 400 mg reduced cleavage of high-molecular-weight kininogen in plasma from patients with hereditary angioedema with C1 inhibitor deficiency to levels approaching that from patients without the disorder. From day 8 to day 50, the 300-mg and 400-mg groups had 100% and 88% fewer attacks, respectively, than the placebo group. All

  10. Cryptogenic sensory polyneuropathy.

    Science.gov (United States)

    Pasnoor, Mamatha; Dimachkie, Mazen M; Barohn, Richard J

    2013-05-01

    Chronic sensory or sensorimotor polyneuropathy is a common cause for referral to neurologists. Despite extensive diagnostic testing, up to one-third of these patients remain without a known cause, and are referred to as having cryptogenic sensory peripheral neuropathy. Symptoms progress slowly. On examination, there may be additional mild toe flexion and extension weakness. Electrophysiologic testing and histology reveals axonal neuropathy. Prognosis is usually favorable, as most patients maintain independent ambulation. Besides patient education and reassurance, management is focused on pharmacotherapy for neuropathic pain and physical therapy for balance training, and, occasionally, assistive devices.

  11. Transcendence and Sensoriness

    DEFF Research Database (Denmark)

    Protestant theology and culture are known for a reserved, at times skeptical, attitude to the use of art and aesthetic forms of expression in a religious context. In Transcendence and Sensoriness, this attitude is analysed and discussed both theoretically and through case studies considered...

  12. Management of hereditary angioedema: 2010 Canadian approach

    Directory of Open Access Journals (Sweden)

    Bowen Tom

    2010-07-01

    Full Text Available Abstract C1-inhibitor (C1-INH deficiency is a rare blood disorder resulting in angioedema attacks that are debilitating and may be life-threatening. Prophylaxis and therapy of events has changed since our first Canadian Consensus Conference on the diagnosis, therapy and management of HAE. We have formed the Canadian Hereditary Angioedema Network (CHAEN/Réseau Canadien d'Angioédème Héréditaire (RCAH - http://www.haecanada.com to advance care of patients with this disorder in Canada. We here present a review of management of HAE in Canada.

  13. Skin deposits in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Blöndal, H; Gudmundsson, G

    1990-01-01

    Clinically normal skin from 47 individuals aged 9-70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic...... individuals, who had the Alu 1 restriction fragment length polymorphism (RFLP) marker reported to cosegregate with the disease, also had cystatin C amyloid deposits in the skin. Three asymptomatic individuals (age 17-46) belonging to the HCCA families were without amyloid in the skin but had Alu 1 RFLP marker...

  14. The arthropathy of hereditary arthroophthalmopathy (Stickler syndrome).

    Science.gov (United States)

    Lewkonia, R M

    1992-08-01

    Hereditary arthroophthalmopathy (Stickler syndrome) is an autosomal dominant syndrome characterized by musculoskeletal, ophthalmic and dysmorphic facial features. A family is described illustrating diverse expressions of Stickler syndrome, including abnormalities not directly attributable to mutation of the type II procollagen gene. A review of the literature demonstrates a range of articular problems, several of which are not specific to Stickler syndrome, and might be encountered in either adult or pediatric rheumatology practice. Stickler syndrome may be underrecognized by rheumatologists, particularly if the significance of nonarticular clinical features or a positive family history are not appreciated.

  15. Platelet Function in Basset Hound Hereditary Thrombopathy.

    Science.gov (United States)

    1986-01-01

    Hematol, 17(4),242-258, 1980. 5. CHARO, I.F., FEINMAN , R.D., DETWILER, T.C. Interrelation of platelet aggregation and secretion. J. Clin. Invest...of dogs affected with Basset Hound Hereditary Thrombopathy. Thromb Au, 3, 61-71, 1985. 4. DETWILER, T.C., CHARO, I.F., AND FEINMAN , R.D. Evidence...glycoproteins. Surv Synth Path Res 1:274, 1983. Charo IF, Feinman RD, and Detwiler TC. Interrelation of platelet aggregation and secretion. J Clin Invest 60

  16. The humanistic burden of hereditary angioedema

    DEFF Research Database (Denmark)

    Caballero, Teresa; Aygören-Pürsün, Emel; Bygum, Anette

    2014-01-01

    and impact of HAE types I and II from the patient perspective. The HAE Burden of Illness Study in Europe was conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective via a one-time survey, which included items on clinical characteristics and physical......Hereditary angioedema (HAE) is a rare but potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The broad range of consequences of HAE on patients? lives is not well understood. The study objective was to comprehensively characterize the burden of illness...

  17. Hereditary mucoepithelial dysplasia and severe respiratory distress

    Directory of Open Access Journals (Sweden)

    Mahmoud Halawa

    2015-01-01

    Full Text Available Hereditary mucoepithelial dysplasia (HMD is a rare autosomal dominant disorder characterized by mucoepithelial disruption of the skin, hair and mucous membranes. It results from defective gap junction formation and leads to non-scarring alopecia, mucosal erythema, perineal erythematous intertrigo, involvement of the conjunctival mucosa, and pulmonary disease. We present a case of severe respiratory distress in an initially healthy full term infant born to a mother with HMD. This infant later developed signs and symptoms of HMD. A high index of suspicion for pulmonary infection with atypical organism is essential in infants with a family history of HMD who present with respiratory distress.

  18. Multiple mechanisms for hereditary sideroblastic anemia.

    Science.gov (United States)

    Furuyama, Kazumichi; Sassa, Shigeru

    2002-02-01

    Hereditary sideroblastic anemia (HSA) is a heterogeneous group of inherited anemic disorders which is characterized by the presence of ringed sideroblasts in the bone marrow, microcytic hypochromic anemia and typically its X-linked inheritance in patients. It has been shown that a deficiency of the erythroid-specific delta-aminolevulinate synthase (ALAS-E) activity is responsible for pyridoxine-responsive HSA in many patients, however, the pathogenesis of other types of HSA remains still unknown. In this article, recent evidence suggesting multiple causes for HSA is summarized and discussed.

  19. Sensory analysis of lipstick.

    Science.gov (United States)

    Yap, K C S; Aminah, A

    2011-06-01

    Sensory analysis of lipstick product by trained panellists started with recruiting female panels who are lipstick users, in good health condition and willing to be a part of sensory members. This group of people was further scrutinized with duo-trio method using commercial lipstick samples that are commonly used among them. About 40% of the 15 panels recruited were unable to differentiate the lipstick samples they usually use better than chance. The balance of nine panels that were corrected at least with 65% across all trials in panels screening process was formed a working group to develop sensory languages as a means of describing product similarities and differences and a scoring system. Five sessions with each session took about 90 min were carried out using 10 types of lipsticks with different waxes mixture ratio in the formulation together with six commercial lipsticks that are the most common to the panels. First session was focus on listing out the panels' perception towards the characteristic of the lipstick samples after normal application on their lips. Second session was focus on the refining and categorizing the responses gathered from the first session and translated into sensory attributes with its definition. Third session was focus on the scoring system. Fourth and fifth sessions were repetition of the third session to ensure consistency. In a collective effort of the panels, sensory attributes developed for lipstick were Spreadability, Off flavour, Hardness, Smoothness, Moist, Not messy, Glossy and Greasy. Analysis of variance was able to provide ample evidence on gauging the panel performance. A proper panels selecting and training was able to produce a reliable and sensitive trained panel for evaluating the product based on the procedures being trained. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  20. Moyamoya Syndrome Associated With Hereditary Spherocytosis: An Emerging Clinical Entity.

    Science.gov (United States)

    Gait-Carr, Eleanor; Connolly, Daniel J A; King, David

    2017-04-01

    Moyamoya syndrome is an unusual cerebrovascular disorder, which has rarely been reported in association with hereditary spherocytosis. We present the case of a 6-year-old boy with hereditary spherocytosis who was diagnosed with Moyamoya syndrome following a stroke. We discuss why these conditions may coexist and briefly outline the management of such children.

  1. [DNA-based diagnosis of hereditary tumour predisposition

    NARCIS (Netherlands)

    Menko, F.H.; Ligtenberg, M.J.L.; Brouwer, T.; Hahn, D.E.; Ausems, M.G.E.M.

    2007-01-01

    Of all forms of cancer, approximately 5% are caused by factors leading to a strong genetic predisposition. DNA diagnosis is currently used in families with hereditary tumour syndromes, such as familial adenomatous polyposis, hereditary non-polyposis colorectal carcinoma (Lynch syndrome), and heredit

  2. [Hereditary haemochromatosis: novel genes, novel diseases and hepcidin

    NARCIS (Netherlands)

    Bergmans, J.P.; Kemna, E.H.J.M.; Janssen, M.C.; Jacobs, E.M.G.; Stalenhoef, A.F.H.; Marx, J.J.M.; Swinkels, D.W.

    2007-01-01

    Since the discovery of the HFE gene of hereditary haemochromatosis in 1996 several new genetic defects have been identified, enabling explanation of the cause and variety of this disease. To date, at least 5 major types of hereditary haemochromatosis have been recognised. All these genes encode for

  3. Cerebral abscesses among Danish patients with hereditary haemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Tørring, P M; Nissen, H;

    2013-01-01

    Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs), which due to paradoxical embolization may cause cerebral abscess.......Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs), which due to paradoxical embolization may cause cerebral abscess....

  4. BRCA1/2 associated hereditary breast cancer

    Institute of Scientific and Technical Information of China (English)

    Li-song TENG; Yi ZHENG; Hao-hao WANG

    2008-01-01

    Breast cancer is one of the leading causes of death in women today. Some of the patients are hereditary, with a large proportion characterized by mutation in BRCA1 and/or BRCA2 genes. In this review, we provide an overview of these two genes,focusing on their relationship with hereditary breast cancers. BRCA1/2 associated hereditary breast cancers have unique features that differ from the general breast cancers, including alterations in cellular molecules, pathological bases, biological behavior, and a different prevention strategy. But the outcome of BRCA1/2 associated hereditary breast cancers still remains controversial;further studies are needed to elucidate the nature of BRCA1/2 associated hereditary breast cancers.

  5. Hereditary Neuropathy with Liability to Pressure Palsy: A Recurrent and Bilateral Foot Drop Case Report

    Directory of Open Access Journals (Sweden)

    Filipa Flor-de-Lima

    2013-01-01

    Full Text Available Hereditary neuropathy with liability to pressure palsy is characterized by acute, painless, recurrent mononeuropathies secondary to minor trauma or compression. A 16-year-old boy had the first episode of right foot drop after minor motorcycle accident. Electromyography revealed conduction block and slowing velocity conduction of the right deep peroneal nerve at the fibular head. After motor rehabilitation, he fully recovered. Six months later he had the second episode of foot drop in the opposite site after prolonged squatting position. Electromyography revealed sensorimotor polyneuropathy of left peroneal, sural, posterior tibial, and deep peroneal nerves and also of ulnar, radial, and median nerves of both upper limbs. Histological examination revealed sensory nerve demyelination and focal thickenings of myelin fibers. The diagnosis of hereditary neuropathy with liability to pressure palsy was confirmed by PMP22 deletion of chromosome 17p11.2. He started motor rehabilitation and avoidance of stressing factors with progressive recovery. After one-year followup, he was completely asymptomatic. Recurrent bilateral foot drop history, “sausage-like” swellings of myelin in histological examination, and the results of electromyography led the authors to consider the diagnosis despite negative family history. The authors highlight this rare disease in pediatric population and the importance of high index of clinical suspicion for its diagnosis.

  6. Clinical features of hereditary spastic paraplegia with thin corpus callosum:report of 5 Chinese cases

    Institute of Scientific and Technical Information of China (English)

    唐北沙; 陈昕; 赵国华; 沈璐; 严新翔; 江泓; 罗巍

    2004-01-01

    Background Hereditary spastic paraplegia is a clinically and genetically heterogeneous group of neurodegenerative disorders of the motor system, characterized by slowly progressive spasticity and weakness of the lower extremities. This study was conducted to investigate the clinical features of hereditary spastic paraplegia with thin corpus callosum (HSP-TCC). Methods Clinical data from five patients and thirty-five previously published case reports of HSP-TCC were analyzed retrospectively. Results Most patients were adolescents at the onset of the disease, presenting with spastic paraparesis of the lower limbs and mental impairment. Some patients also had other clinical features, including spasticity of the upper limbs, cerebellar ataxia, and sensory disturbances. Cranial MRIs of the five patients revealed an extremely thin corpus callosum, sometimes with widened cerebral sulci and ventricles, as well as with cerebellar and cerebral atrophy. Conclusion The main clinical features of HSP-TCC include slowly progressive spastic paraplegia, mental impairment during the second decade of life, and an extremely thin corpus callosum as shown on cranial MRIs.

  7. [Analysis of the clinical, electrophysiological and genetic features of a family affected with hereditary neuropathy with liability to pressure palsies].

    Science.gov (United States)

    Qi, Faying; Che, Fengyuan

    2015-02-01

    To delineate the clinical, electrophysiological and genetics features of a family where 4 members were affected with hereditary neuropathy with liability to pressure palsies (HNPP). Clinical features of the 4 patients were summarized. Electrophysiological examination and genetic analysis were carried out. All of the patients showed recurrent motor and sensory disturbances after minor traction or constriction. Electrophysiology study revealed that the prolonged latency and reduced conduction velocity of peripheral nerve were general and with multiple sites of affection. The nerve locations liable to entrapment showed conduction block. A deletion mutation of peripheral myelin protein 22 (PMP22) gene was identified by genetic analysis. HNPP usually affects areas where nerves are liable to entrapment, and presents with motor and sensory disturbances of the innervated areas. Electrophysiological study reveals general nervous demyelination. Genetic analysis can clarify the diagnosis of HNPP.

  8. Perinatal Gjb2 gene transfer rescues hearing in a mouse model of hereditary deafness.

    Science.gov (United States)

    Iizuka, Takashi; Kamiya, Kazusaku; Gotoh, Satoru; Sugitani, Yoshinobu; Suzuki, Masaaki; Noda, Tetsuo; Minowa, Osamu; Ikeda, Katsuhisa

    2015-07-01

    Hearing loss is the most widespread sensory disorder, with an incidence of congenital genetic deafness of 1 in 1600 children. For many ethnic populations, the most prevalent form of genetic deafness is caused by recessive mutations in the gene gap junction protein, beta 2, 26 kDa (GJB2), which is also known as connexin 26 (Cx26). Despite this knowledge, existing treatment strategies do not completely recover speech perception. Here we used a gene delivery system to rescue hearing in a mouse model of Gjb2 deletion. Mice lacking Cx26 are characterized by profound deafness from birth and improper development of cochlear cells. Cochlear delivery of Gjb2 using an adeno-associated virus significantly improved the auditory responses and development of the cochlear structure. Using gene replacement to restore hearing in a new mouse model of Gjb2-related deafness may lead to the development of therapies for human hereditary deafness.

  9. Understanding Sensory Integration. ERIC Digest.

    Science.gov (United States)

    DiMatties, Marie E.; Sammons, Jennifer H.

    This brief paper summarizes what is known about sensory integration and sensory integration dysfunction (DSI). It outlines evaluation of DSI, treatment approaches, and implications for parents and teachers, including compensatory strategies for minimizing the impact of DSI on a child's life. Review of origins of sensory integration theory in the…

  10. Leber hereditary optic neuropathy: current perspectives

    Directory of Open Access Journals (Sweden)

    Meyerson C

    2015-06-01

    Full Text Available Cherise Meyerson, Greg Van Stavern, Collin McClelland Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO, USA Abstract: Leber hereditary optic neuropathy (LHON is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells. Keywords: Leber hereditary optic neuropathy, mitochondria, neuro-ophthalmology, mitochondrial DNA

  11. Epidemiology of non-hereditary angioedema.

    Science.gov (United States)

    Madsen, Flemming; Attermann, Jørn; Linneberg, Allan

    2012-09-01

    The prevalence of non-hereditary angioedema was investigated in a general population sample (n = 7,931) and in a sample of Danish patients (n = 7,433) tested for deficiency of functional complement C(1) esterase inhibitor protein (functional C(1) INH). The general population sample (44% response rate) reported a lifetime prevalence of 7.4% for angioedema. In both groups symptoms were most frequent in the lips, head, neck, eyes and tongue. In the C(1) INH test normal group angioedema was still active at the time of the study in 53% of the patients, and 36% reported symptoms in the throat, 23% in the abdominal area, 17% had diarrhoea, 11% had vomiting and 6% fainted during attacks. Non-hereditary angioedema has high lifetime prevalence and becomes chronic in approximately 50% of affected patients. Symptoms in the larynx and throat, as well as non-specific symptoms, such as dizziness and abdominal pain, were more frequent than previously reported.

  12. Epidemiology of Non-hereditary Angioedema

    DEFF Research Database (Denmark)

    Madsen, Flemming; Attermann, Jørn; Linneberg, Allan

    2012-01-01

    The prevalence of non-hereditary angioedema was investigated in a general population sample (n¿=¿7,931) and in a sample of Danish patients (n¿=¿7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). The general population sample (44% response rate......% in the abdominal area, 17% had diarrhoea, 11% had vomiting and 6% fainted during attacks. Non-hereditary angioedema has high lifetime prevalence and becomes chronic in approximately 50% of affected patients. Symptoms in the larynx and throat, as well as non-specific symptoms, such as dizziness and abdominal pain......) reported a lifetime prevalence of 7.4% for angioedema. In both groups symptoms were most frequent in the lips, head, neck, eyes and tongue. In the C1 INH test normal group angioedema was still active at the time of the study in 53% of the patients, and 36% reported symptoms in the throat, 23...

  13. HEREDITARY FRUCTOSE INTOLERANCE – CASE REPORT

    Directory of Open Access Journals (Sweden)

    Jernej Brecelj

    2002-03-01

    Full Text Available Background. Hereditary fructose intolerance is a rare inborn error of carbohydrate metabolism that presents with hypoglicemia, metabolic acidosis and liver decompensation when the patient is exposed to fructose. Diagnosis was established by fructose tolerance test in the past and nowadays mostly by determination of deficient enzyme fructose-1phosphate aldolase (aldolase B activity in hepatic tissue or by molecular genetic means if the mutation is known. Treatment involves elimination (in infants or reduction of fructose and sucrose from the diet and results in improvement in the patient’s clinical status and liver disease.Results. This article presents a patient with hereditary fructose intolerance who was diagnosed 18 years ago on the Department of Pediatric Gastroenterology, Ljubljana Children’s Hospital. At that time oral fructose tolerance test was used to diagnose the disorder. When she was 17 we performed liver biopsy. The enzyme determination showed the absence of aldolase B activity.Conclusions. Only cooperation of different experts enables recognition of rare metabolic disorders which must be prompt to prevent further damage.

  14. Instabilities in sensory processes

    Science.gov (United States)

    Balakrishnan, J.

    2014-07-01

    In any organism there are different kinds of sensory receptors for detecting the various, distinct stimuli through which its external environment may impinge upon it. These receptors convey these stimuli in different ways to an organism's information processing region enabling it to distinctly perceive the varied sensations and to respond to them. The behavior of cells and their response to stimuli may be captured through simple mathematical models employing regulatory feedback mechanisms. We argue that the sensory processes such as olfaction function optimally by operating in the close proximity of dynamical instabilities. In the case of coupled neurons, we point out that random disturbances and fluctuations can move their operating point close to certain dynamical instabilities triggering synchronous activity.

  15. Sensory Perception: Lessons from Synesthesia

    Science.gov (United States)

    Harvey, Joshua Paul

    2013-01-01

    Synesthesia, the conscious, idiosyncratic, repeatable, and involuntary sensation of one sensory modality in response to another, is a condition that has puzzled both researchers and philosophers for centuries. Much time has been spent proving the condition’s existence as well as investigating its etiology, but what can be learned from synesthesia remains a poorly discussed topic. Here, synaesthesia is presented as a possible answer rather than a question to the current gaps in our understanding of sensory perception. By first appreciating the similarities between normal sensory perception and synesthesia, one can use what is known about synaesthesia, from behavioral and imaging studies, to inform our understanding of “normal” sensory perception. In particular, in considering synesthesia, one can better understand how and where the different sensory modalities interact in the brain, how different sensory modalities can interact without confusion ― the binding problem ― as well as how sensory perception develops. PMID:23766741

  16. Brazilian guidelines for the diagnosis and treatment of hereditary angioedema.

    Science.gov (United States)

    Giavina-Bianchi, Pedro; França, Alfeu T; Grumach, Anete S; Motta, Abílio A; Fernandes, Fátima R; Campos, Regis A; Valle, Solange O; Rosário, Nelson A; Sole, Dirceu

    2011-01-01

    Hereditary angioedema is an autosomal dominant disease characterized by edema attacks with multiple organ involvement. It is caused by a quantitative or functional deficiency of the C1 inhibitor, which is a member of the serine protease inhibitor family. Hereditary angioedema is unknown to many health professionals and is therefore an underdiagnosed disease. The causes of death from hereditary angioedema include laryngeal edema with asphyxia. The estimated mortality rate in patients in whom the disease goes undetected and who are therefore incorrectly treated is 25-40%. In addition to edema of the glottis, hereditary angioedema often results in edema of the gastrointestinal tract, which can be incapacitating. Patients with hereditary angioedema may undergo unnecessary surgical interventions because the digestive tract can be the primary or only organ system involved, thus mimicking acute surgical abdomen. It is estimated that patients with hereditary angioedema experience some degree of disability 20-100 days per year. The Experts in Clinical Immunology and Allergy of the "Associação Brasileira de Alergia e Imunopatologia -ASBAI" developed these guidelines for the diagnosis, therapy, and management of hereditary angioedema.

  17. Brazilian guidelines for the diagnosis and treatment of hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Pedro Giavina-Bianchi

    2011-01-01

    Full Text Available Hereditary angioedema is an autosomal dominant disease characterized by edema attacks with multiple organ involvement. It is caused by a quantitative or functional deficiency of the C1 inhibitor, which is a member of the serine protease inhibitor family. Hereditary angioedema is unknown to many health professionals and is therefore an underdiagnosed disease. The causes of death from hereditary angioedema include laryngeal edema with asphyxia. The estimated mortality rate in patients in whom the disease goes undetected and who are therefore incorrectly treated is 25-40%. In addition to edema of the glottis, hereditary angioedema often results in edema of the gastrointestinal tract, which can be incapacitating. Patients with hereditary angioedema may undergo unnecessary surgical interventions because the digestive tract can be the primary or only organ system involved, thus mimicking acute surgical abdomen. It is estimated that patients with hereditary angioedema experience some degree of disability 20-100 days per year. The Experts in Clinical Immunology and Allergy of the "Associação Brasileira de Alergia e Imunopatologia -ASBAI" developed these guidelines for the diagnosis, therapy, and management of hereditary angioedema.

  18. Hereditary red cell membrane disorders and laboratory diagnostic testing.

    Science.gov (United States)

    King, M-J; Zanella, A

    2013-06-01

    This overview describes two groups of nonimmune hereditary hemolytic anemias caused by defects in membrane proteins located in distinct layers of the red cell membrane. Hereditary spherocytosis (HS), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP) represent disorders of the red cell cytoskeleton. Hereditary stomatocytoses represents disorders of cation permeability in the red cell membrane. The current laboratory screening tests for HS are the osmotic fragility test, acid glycerol lysis time test (AGLT), cryohemolysis test, and eosin-5'-maleimide (EMA)-binding test. For atypical HS, SDS-polyacrylamide gel electrophoresis of erythrocyte membrane proteins is carried out to confirm the diagnosis. The diagnosis of HE/HPP is based on abnormal red cell morphology and the detection of protein 4.1R deficiency or spectrin variants using gel electrophoresis. None of screening tests can detect all HS cases. Some testing centers (a survey of 25 laboratories) use a combination of tests (e.g., AGLT and EMA). No specific screening test for hereditary stomatocytoses is available. The preliminary diagnosis is based on presenting a compensated hemolytic anemia, macrocytosis, and a temperature or time dependent pseudohyperkalemia in some patients. Both the EMA-binding test and the osmotic fragility test may help in differential diagnosis of HS and hereditary stomatocytosis.

  19. Rapid genetic screening of Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies patients

    Institute of Scientific and Technical Information of China (English)

    Xiaobo Li; Kun Xia; Beisha Tang; Ruxu Zhang; Xiaohong Zi; Lin Li; Yajing Zhan; Shunxiang Huang; Jin Li; Xuning Li; Xigui Li; Zhengmao Hu

    2012-01-01

    We used the allele-specific PCR-double digestion method on peripheral myelin protein 22 (PMP22) to determine duplication and deletion mutations in the proband and family members of one family with Charcot-Marie-Tooth disease type 1 and one family with hereditary neuropathy with liability to pressure palsies. The proband and one subclinical family member from the Charcot-Marie-Tooth disease type 1 family had a PMP22 gene duplication; one patient from the hereditary neuropathy with liability to pressure palsies family had a PMP22 gene deletion. Electron microscopic analysis of ultrathin sections of the superficial peroneal nerve from the two probands demonstrated demyelination and myelin sheath hyperplasia, as well as an ‘onion-like’ structure in the Charcot-Marie-Tooth disease type 1A patient. We observed an irregular thickened myelin sheath and ‘mouse-nibbled’-like changes in the patient with hereditary neuropathy with liability to pressure palsies. In the Charcot-Marie-Tooth disease type 1A patient, nerve electrophysiological examination revealed moderate-to-severe reductions in the motor and sensory conduction velocities of the bilateral median nerve, ulnar nerve, tibial nerve, and sural nerve. Moreover, the compound muscle action potential amplitude was decreased. In the patient with hereditary neuropathy with liability to pressure palsies, the nerve conduction velocity of the bilateral tibial nerve and sural nerve was moderately reduced, and the nerve conduction velocity of the median nerve and ulnar nerve of both upper extremities was slightly reduced.

  20. Monoclonal gammopathy in hereditary spherocytosis: Possible pathogenetic relation

    Energy Technology Data Exchange (ETDEWEB)

    Schafer, A.I. (Univ. of Chicago); Miller, J.B.; Lester, E.P.; Bowers, T.K.; Jacob, H.S.

    1978-01-01

    Two cases of monoclonal gammopathy in patients with hereditary spherocytosis led us to consider the possible pathogenetic relation between these two disorders. Twelve adult patients with hereditary spherocytosis had significant hypergammaglobulinemia in comparison to normal subjects. Retrospective analysis of previous illness in 140 patients with multiple myeloma showed a significant association between IgA myeloma and previous gallbladder disease. We propose that the chronic reticuloendothelial stimulation due to extravascular hemolysis, possibly potentiated by the inflammation associated with cholelithiasis and cholecystitis, may foster neoplastic transformation of immunocytes in patients with hereditary spherocytosis, ultimately leading to the development of monoclonal gammopathy.

  1. Diagnosis and Management of Hereditary Renal Cell Cancer.

    Science.gov (United States)

    Menko, Fred H; Maher, Eamonn R

    2016-01-01

    Renal cell cancer (RCC) is the common denominator for a heterogeneous group of diseases. The subclassification of these tumours is based on histological type and molecular pathogenesis. Insight into molecular pathogenesis has led to the development of targeted systemic therapies. Genetic susceptibility is the principal cause of RCC in about 2-4% of cases. Hereditary RCC is the umbrella term for about a dozen different conditions, the most frequent of which is von Hippel-Lindau disease . Here, we describe the main hereditary RCC syndromes, consider criteria for referral of RCC patients for clinical genetic assessment and discuss management options for patients with hereditary RCC and their at-risk relatives.

  2. Hereditary optic neuropathies share a common mitochondrial coupling defect.

    Science.gov (United States)

    Chevrollier, Arnaud; Guillet, Virginie; Loiseau, Dominique; Gueguen, Naïg; de Crescenzo, Marie-Anne Pou; Verny, Christophe; Ferre, Marc; Dollfus, Hélène; Odent, Sylvie; Milea, Dan; Goizet, Cyril; Amati-Bonneau, Patrizia; Procaccio, Vincent; Bonneau, Dominique; Reynier, Pascal

    2008-06-01

    Hereditary optic neuropathies are heterogeneous diseases characterized by the degeneration of retinal ganglion cells leading to optic nerve atrophy and impairment of central vision. We found a common coupling defect of oxidative phosphorylation in fibroblasts of patients affected by autosomal dominant optic atrophy (mutations of OPA1), autosomal dominant optic atrophy associated with cataract (mutations of OPA3), and Leber's hereditary optic neuropathy, a disorder associated with point mutations of mitochondrial DNA complex I genes. Interestingly, the energetic defect was significantly more pronounced in Leber's hereditary optic neuropathy and autosomal dominant optic atrophy patients with a more complex phenotype, the so-called plus phenotype.

  3. Prevalence of pulmonary hypertension in hereditary spherocytosis.

    Science.gov (United States)

    Crary, Shelley E; Ramaciotti, Claudio; Buchanan, George R

    2011-12-01

    Vascular complications, including pulmonary hypertension (PH), have been reported to occur following splenectomy for various disorders,including hereditary spherocytosis (HS). We performed a prospective cross-sectional study of 36 adults with HS (78% with prior splenectomy)utilizing echocardiography to estimate tricuspid regurgitant jet velocity (TRV) as well as measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) to screen for PH. No participant with HS hada significantly elevated TRV or NT-proBNP level, despite a median 25-year interval since splenectomy (95% confidence interval for point prevalence 0, 0.097). Although our study was limited by a small sample size, it appears that persons with HS, following splenectomy, appear unlikely to be at significantly increased risk of developing PH to the degree reported for thalassemia and sickle cell disease

  4. Hereditary gingival fibromatosis with distinctive facies.

    Science.gov (United States)

    Prasad, Sunkara Shree Ramalinga; Radharani, Chitturi; Sinha, Soumya; Kumar, Sv Kiran

    2012-11-01

    Hereditary gingival enlargement also known as gingivitis or familial elephantiasis is a rare type of gingival enlargement. It appears as an isolated autosomal dominant disorder or maybe associated with other conditions. Oral manifestations may vary from minimal involvement of only tuberosity area and the buccal gingiva around the lower molars to a generalized enlargement inhibiting eruption of the teeth. This paper discusses the case of a 13-year-old female patient with distinctive facial characteristics who presented to the department with a chief complaint of swollen gums since 1 year. She had severe diffuse gingival enlargement of the maxilla and mandible. Diagnosis was made based upon clinical examination and family history. Quadrant wise internal bevel gingivectomy procedure was done for the patient to restore her functional and esthetic needs.

  5. Hereditary palmoplantar keratodermas in South India.

    Science.gov (United States)

    Gulati, S; Thappa, D M; Garg, B R

    1997-12-01

    Thirty-one patients with inherited palmoplantar keratodermas (PPKs) were screened from 59,490 cases who visiting the OPD of JIPMER, Pondicherry. The prevalence rate was 5.2 per 10,000 population (1:2000 approx.). PPKs were more common in males (25 patients) than females (6 patients); the overall male to female ratio was 4.2:1. The incidence was highest in the group from 0-10 years of life (67.7% of cases). Unna-Thost syndrome topped the list with 38.7% of cases and its prevalence 1:6000 (approx.), followed by Greither's disease (22.9%) and others-Vohwinkel (3 cases), idiopathic punctate (2 cases), ichthyosis vulgaris associated PPK (2 cases) etc. This study has for the first time reported the prevalence and patterns of hereditary PPKs in South India.

  6. [Progress with management of hereditary angioedema].

    Science.gov (United States)

    Johnston, D T; Lode, H

    2013-03-21

    Hereditary angioedema (HAE) is a rare type of angioedema caused by a quantitative or functional deficit of C1 inhibitor (C1 INH) that leads to excess production of bradykinin, which can result in acute localized swelling attacks in the skin or mucous membranes of the mouth, head and neck, extremities, gastrointestinal (GI) tract, genitals, trunk, and larynx. Angioedema in the respiratorytract maycause airway obstruction; severe abdominal pain, vomiting, or diarrhea may occur in the GI tract. Patients with HAE may be diagnosed and managed by HAE specialists or by primary care physicians depending on individual circumstances. Proper treatment requires differentiation from other forms of angioedema. Patients with HAE who are managed appropriately with medications that treat and prevent atttacks may have a lower risk of death from laryngeal edema and a better quality of life. Less frequent attacks may allow them to attend work, school, and leisure activities more regularlyand be free of the pain and disfigurement of HAE attacks moreoften.

  7. Dementia in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Blöndal, H; Guomundsson, G; Benedikz, Eirikur

    1989-01-01

    Nineteen cases with verified Hereditary Cystatin C Amyloid Angiopathy are presented. All of the cases had one or more cerebrovascular insults starting at the age of 20-41 years and survived from 10 days to 23 years after the first insult. Progressive dementia was a prominent clinical feature...... in seventeen cases of whom two presented with dementia. At the last examination the majority had severe dementia and severely abnormal EEG. Anti-cystatin C positive amyloid vascular and perivascular infiltrates were found. The resulting damage to the microvasculature of the brain and secondary hemorrhages...... and infarctions were considered to be an adequate explanation for the dementia in these cases. Skin biopsies can now probably be used to demonstrate cystatin C positive amyloid deposits conclusively in the tissues of these patients....

  8. Occurrence of hereditary bullous epidermolyses in Croatia.

    Science.gov (United States)

    Pavicić, Z; Kmet-Vizintin, P; Kansky, A; Dobrić, I

    1990-06-01

    To determine the occurrence of hereditary bullous epidermolyses (EB) in Croatia, Yugoslavia, from 1960 to 1987, cases were gathered from the hospital files of dermatologic and pediatric clinics and departments throughout the area. The diagnosis of EB type was made on the basis of clinical features, patients' histories, and light microscopy and electron microscopy findings. Fifty families with 58 patients were registered; 44 patients were examined personally by one of the authors. The most frequent type of EB in Croatia was recessive dystrophic EB Hallopeau-Siemens, occurring in 35 of the 58 individuals. Regional accumulation of cases within the Varazdin area was noted (13 patients). Prevalence of EB in Croatia is 0.956 cases per 100,000 inhabitants. One case of recessive dystrophic EB Hallopeau-Siemens occurred in about every 52,000 live births.

  9. [Research progress of Leber hereditary optic neuropathy].

    Science.gov (United States)

    Zhang, A-Mei; Yao, Yong-Gang

    2013-02-01

    Leber hereditary optic neuropathy (LHON; MIM 535000) is one of the most common mitochondrial diseases, with a clinical manifestation of painless, acute or sub-acute bilateral visual loss in young adults leading to blindness and central scotoma. Over 95% of LHON patients were caused by one of three primary mtDNA mutations (m.11778G>A, m.3460G>A and m.14484T>C). Incomplete penetrance and gender bias are two riddles of this disease. Here we summarized recent research progress of LHON, with a focus on the molecular pathogenic mechanisms, clinical features, in vitro experiments and animal models, and prevention and treatment of LHON. In particular, we presented the main findings and challenges in our recent efforts to decipher genetic susceptibility and mechanism of LHON in Chinese patients.

  10. Idebenone for Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Gueven, N

    2016-03-01

    Idebenone is a rapidly absorbed, safe and well-tolerated drug and is currently the only clinically proven treatment option for Leber's hereditary optic neuropathy (LHON) patients. Idebenone (Raxone®) is approved by the European Medicines Agency for the treatment of LHON and has been available on the European market since 2015. Due to its molecular mode of action of bypassing the defective mitochondrial complex I, idebenone leads to improved energy supply and a functional recovery of retinal ganglion cells during the acute stage of the disease, thereby preventing further vision loss and promoting recovery of vision. Thus, commencing treatment shortly after the onset of symptoms is likely to have the best therapeutic effect, a hypothesis that is supported by the available clinical data.

  11. Skin deposits in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Blöndal, H; Gudmundsson, G

    1990-01-01

    Clinically normal skin from 47 individuals aged 9-70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic...... individuals, who had the Alu 1 restriction fragment length polymorphism (RFLP) marker reported to cosegregate with the disease, also had cystatin C amyloid deposits in the skin. Three asymptomatic individuals (age 17-46) belonging to the HCCA families were without amyloid in the skin but had Alu 1 RFLP marker....... Skin from 12 individuals who served as controls and skin from 14 close relatives of the patients was negative for amyloid. Punch biopsy of the skin is a simple procedure which is of value for the diagnosis of HCCA, even before the appearance of clinical symptoms. This method might also be of use...

  12. Pulmonary hypertension in hereditary haemorrhagic telangiectasia

    Institute of Scientific and Technical Information of China (English)

    Veronique; MM; Vorselaars; Sebastiaan; Velthuis; Repke; J; Snijder; Jan; Albert; Vos; Johannes; J; Mager; Martijn; C; Post

    2015-01-01

    Hereditary haemorrhagic telangiectasia(HHT) is an autosomal dominant inherited disorder characterised by vascular malformations in predominantly the brain,liverand lungs.Pulmonary hypertension(PH) is increasingly recognised as a severe complication of HHT.PH may be categorised into two distinct types in patients with HHT.Post-capillary PH most often results from a high pulmonary blood flow that accompanies the high cardiac output state associated with liver arteriovenous malformations.Less frequently,the HHT-related gene mutations in ENG or ACVRL1 appear to predispose patients with HHT to develop pre-capillary pulmonary arterial hypertension.Differentiation between both forms of PH by right heart catheterisation is essential,since both entities are associated with severe morbidity and mortality with different treatment options.Therefore all HHT patients should be referred to an HHT centre.

  13. Dementia in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Blöndal, H; Guomundsson, G; Benedikz, Eirikur

    1989-01-01

    Nineteen cases with verified Hereditary Cystatin C Amyloid Angiopathy are presented. All of the cases had one or more cerebrovascular insults starting at the age of 20-41 years and survived from 10 days to 23 years after the first insult. Progressive dementia was a prominent clinical feature...... in seventeen cases of whom two presented with dementia. At the last examination the majority had severe dementia and severely abnormal EEG. Anti-cystatin C positive amyloid vascular and perivascular infiltrates were found. The resulting damage to the microvasculature of the brain and secondary hemorrhages...... and infarctions were considered to be an adequate explanation for the dementia in these cases. Skin biopsies can now probably be used to demonstrate cystatin C positive amyloid deposits conclusively in the tissues of these patients....

  14. [Hereditary spastic paraplegia: up to date].

    Science.gov (United States)

    Takiyama, Yoshihisa

    2014-01-01

    Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders that are clinically characterized by progressive spasticity and weakness of the lower limbs. HSP genetic loci are designated SPG1-72 in order of their discovery. In 206 Japanese families with autosomal dominant HSP, SPG4 was the most common form, accounting for 38%, followed by SPG3A (5%), SPG31 (5%), SPG10 (2%), and SPG8 (1%). We have identified novel mutations in the C12orf65 gene and the LYST gene in several Japanese families with autosomal recessive HSP. JASPAC will facilitate gene discovery and mechanistic understanding of HSP. The future challenge will be the establishment of treatment of HSP.

  15. Sensory syndromes in parietal stroke.

    Science.gov (United States)

    Bassetti, C; Bogousslavsky, J; Regli, F

    1993-10-01

    We studied 20 patients with an acute parietal stroke with hemisensory disturbances but no visual field deficit and no or only slight motor weakness, without thalamic involvement on CT or MRI and found three main sensory syndromes. (1) The pseudothalamic sensory syndrome consists of a faciobrachiocrural impairment of elementary sensation (touch, pain, temperature, vibration). All patients have an inferior-anterior parietal stroke involving the parietal operculum, posterior insula, and, in all but one patient, underlying white matter. (2) The cortical sensory syndrome consists of an isolated loss of discriminative sensation (stereognosis, graphesthesia, position sense) involving one or two parts of the body. These patients show a superior-posterior parietal stroke. (3) The atypical sensory syndrome consists of a sensory loss involving all modalities of sensation in a partial distribution. Parietal lesions of different topography are responsible for this clinical picture, which probably represents a minor variant of the two previous sensory syndromes. Neuropsychological dysfunction was present in 17 patients. The only constant association was between conduction aphasia and right-sided pseudothalamic sensory deficit. We conclude that parietal stroke can cause different sensory syndromes depending on the topography of the underlying lesion. Sensory deficits can be monosymptomatic but never present as a "pure sensory stroke" involving face, arm, leg, and trunk together.

  16. The Pathology of Hereditary Breast Cancer

    Directory of Open Access Journals (Sweden)

    Honrado Emiliano

    2004-07-01

    Full Text Available Abstract Several studies have demonstrated that familial breast cancers associated with BRCA1 or BRCA2 germline mutations differ in their morphological and immunohistochemical characteristics. Cancers associated with BRCA1 are poorly differentiated infiltrating ductal carcinomas (IDCs with higher mitotic counts and pleomorphism and less tubule formation than sporadic tumours. In addition, more cases with the morphological features of typical or atypical medullary carcinoma are seen in these patients. Breast carcinomas from BRCA2 mutation carriers tend to be of higher grade than sporadic age-matched controls. Regarding immunophenotypic features. BRCA1 tumours have been found to be more frequently oestrogen receptor- (ER and progesterone receptor-(PR negative, and p53-positive than age-matched controls, whereas these differences are not usually found in BRCA2-associated tumours. A higher frequency and unusual location of p53 mutations have been described in BRCA1/2 carcinomas. Furthermore, BRCA1- and BRCA2-associated breast carcinomas show a low frequency of HER-2 expression. Recent studies have shown that most BRCA1 carcinomas belong to the basal cell phenotype, a subtype of high grade, highly proliferating ER/HER2-negative breast carcinoma characterized by the expression of basal or myoepithelial markers, such as basal keratins, P-cadherin, EGFR, etc. This phenotype occurs with a higher incidence in BRCA1 tumours than in sporadic carcinomas and is rarely found in BRCA2 carcinomas. Hereditary carcinomas not attributable to BRCA1/2 mutations have phenotypic similarities with BRCA2 tumours, but tend to be of lesser grade and lower proliferation index. The pathological features of hereditary breast cancer can drive specific treatment and influence the process of mutation screening.

  17. Hereditary Lymphedema of the Leg – A Case Report

    Directory of Open Access Journals (Sweden)

    Birgit Heinig

    2017-07-01

    Full Text Available Primary of hereditary lymphedema is a rare but progressive disease. It is yet not curable. We present a 48-year-old male patient with hereditary lymphedema of his left leg, that was realised by minor trauma (able twist when he was seven years old. He had never been treated for lymphedema but experienced multiple erysipelas during his life. After diagnostic procedures to exclude other causes of leg swelling, the diagnosis of hereditary lymphedema of the leg, stage III was confirmed. We initialized complex decongestive therapy. During two weeks of intensive treatment, the circumference of the left leg could be reduced by 10 cm. This case illustrates the "natural course" hereditary lymphedema. But it raises the hope that even after decades of ignorance, the patients benefits from complex decongestive treatment. Therapeutic nihilism is unnecessary and poses lymphedema patients to risks of infection and secondary malignancies like Stewart-Trewes syndrome.

  18. Deranged Wnt signaling is frequent in hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Isinger-Ekstrand, Anna; Therkildsen, Christina; Bernstein, Inge

    2011-01-01

    The Wnt signaling pathway is frequently deranged in colorectal cancer and is a key target for future preventive and therapeutic approaches. Colorectal cancers associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome are characterized by wide-spread microsatellite instability...

  19. Sensory Ecology, Evolution, and Behavior

    Institute of Scientific and Technical Information of China (English)

    Martin STEVENS; Guest Editor

    2010-01-01

    @@ 1 Introduction Sensory ecology deals with how animals capture in formation from their environment, and the sensory sys tems involved in doing so (Hailman, 1977; Lythgoe, 1979; Dusenbery, 1992; Mappes and Stevens 2010). Although the term sensory ecology itself is compara tively recent, its basis has a long history, in part due to numerous links with subjects such as neurobiology, physiology, ethology, and evolutionary behavioral ecology.

  20. [Hereditary spherocytosis: Review. Part I. History, demographics, pathogenesis, and diagnosis].

    Science.gov (United States)

    Donato, Hugo; Crisp, Renée Leonor; Rapetti, María Cristina; García, Eliana; Attie, Myriam

    2015-01-01

    Hereditary spherocytosis is the most frequent hereditary anemia excluding beta thalassemia in Argentina. Historical, demographic, genetic and pathogenic aspects of the disease are reviewed, and confirmatory laboratory tests are described. Special characteristics on the outcome of the disease in our population and prevalent protein deficiencies in our country are described. Emphasis is given on new available laboratory tests, which allow an earlier diagnosis using volume of blood samples significantly smaller than required for conventional tests.

  1. An adolescent with hereditary spherocytosis who presented with splenic infarction.

    Science.gov (United States)

    Jones, Lara; Refai, Zafer; Linney, Mike

    2015-07-02

    A 16-year-old male patient with known hereditary spherocytosis presented with a 4-day history of chest pain and lethargy. On admission, he had a low-grade fever and was grossly anaemic; examination revealed splenomegaly. An ultrasound scan confirmed splenomegaly with areas of splenic infarction. Subsequent tests suggested possible Epstein-Barr virus infection. The patient recovered well and had a functional spleen on discharge. This case report presents an unusual complication of isolated hereditary spherocytosis.

  2. Pyoderma Gangrenosum in a Patient with Hereditary Spherocytosis.

    Science.gov (United States)

    Kwon, Hyoung Il; Paek, Jun Oh; Kim, Jeoung Eun; Ro, Young Suck; Ko, Joo Yeon

    2016-03-01

    Pyoderma gangrenosum (PG) is a rare, relapsing cutaneous disease with 4 distinctive clinical manifestations: ulcerative, bullous, pustular, and vegetative lesions. It mainly occurs in adults and is frequently associated with systemic diseases, most commonly inflammatory bowel disease, rheumatologic disease, or hematological dyscrasias. However, there have been no previous reports of PG in a patient with hereditary spherocytosis, a common inherited hemolytic anemia. We report here a unique case of PG in a 15-year-old boy with underlying hereditary spherocytosis.

  3. Acute edema blisters in a hereditary angioedema cutaneous attack.

    Science.gov (United States)

    Fernández Romero, D; Di Marco, P; Malbrán, A

    2008-01-01

    Hereditary angioedema is a rare autosomal dominant disease characterized by recurrent episodes of acute edema affecting the skin and the respiratory and digestive tracts. Acute edema blisters or hydro-static bullae develop after rapid accumulation of interstitial fluid usually associated to cardiac insufficiency. Lesions contain sterile fluid and break up easily resolving without scars. Blisters disappear when fluid accumulation resolves. We describe a patient developing recurrent acute edema blisters as a consequence of cutaneous hereditary angioedema attacks.

  4. Systemic treatment for hereditary cancers: a 2012 update

    OpenAIRE

    Imyanitov, Evgeny N; Byrski, Tomasz

    2013-01-01

    The history of specific therapy for hereditary tumors dates back to mid 1980s and involves a number of reports demonstrating regression of familial colon polyps upon administration of sulindac. Virtually no clinical studies on other hereditary cancer types were available until the year 2009, when Byrski et al. presented the data on unprecedented sensitivity of BRCA1-associated breast malignancies to cisplatin. This breakthrough has revived interest to the treatment of cancer in germ-line muta...

  5. Multi-sensory Sculpting (MSS)

    DEFF Research Database (Denmark)

    von Wallpach, Sylvia; Kreuzer, Maria

    2013-01-01

    -conscious and modality-specific level and use multi-sensory metaphors to express embodied knowledge. Retrieving embodied brand knowledge requires methods that (a) stimulate various senses that have been involved in brand knowledge formation and (b) give consumers the opportunity to express themselves metaphorically...... in a format similar to their cognitive representations. This article introduces multi-sensory sculpting (MSS) as a method that allows retrieving embodied brand knowledge via multi-sensory metaphors and proposes a multi-layered metaphor analysis procedure to interpret these multi-sensory data. The paper...

  6. SENSORY AND CONSUMER TESTING LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — These laboratories conduct a wide range of studies to characterize the sensory properties of and consumer responses to foods, beverages, and other consumer products....

  7. Hereditary opalescent dentin: a report of two cases.

    Science.gov (United States)

    Gupta, Siddharth; Bhowate, Rahul R; Bhati, Ashok

    2010-07-01

    The aim of this case report is to present the clinical and radiographic findings of hereditary opalescent dentin to facilitate an early diagnosis. Hereditary opalescent dentin (or dentinogenesis imperfecta) may manifest itself in three variations: i.e., Shields type I, Shields type II, and Shields type III. Dentinogenesis imperfecta occurs as an autosomal dominant trait with variable expressivity, either in presence with osteogenesis imperfecta or as a separate clinical entity in persons who have none of the features of osteogenesis imperfecta. A seven-year old boy and his mother were both diagnosed with hereditary opalescent dentin. A review of the family dental history revealed that this condition affected not only the child's mother but his maternal grandfather and great grandfather. Both the son and the mother exhibited the same clinical and radiologic features as those reported previously with no evidence of osteogenesis imperfecta. Being an autosomal disease, hereditary opalescent dentin runs in the family and can affect both the deciduous and permanent dentitions as a dominant trait. Once a patient is diagnosed with hereditary opalescent dentin, other family members should be evaluated given the condition is hereditary.

  8. Sensory receptors in monotremes.

    Science.gov (United States)

    Proske, U; Gregory, J E; Iggo, A

    1998-01-01

    This is a summary of the current knowledge of sensory receptors in skin of the bill of the platypus, Ornithorhynchus anatinus, and the snout of the echidna, Tachyglossus aculeatus. Brief mention is also made of the third living member of the monotremes, the long-nosed echidna, Zaglossus bruijnii. The monotremes are the only group of mammals known to have evolved electroreception. The structures in the skin responsible for the electric sense have been identified as sensory mucous glands with an expanded epidermal portion that is innervated by large-diameter nerve fibres. Afferent recordings have shown that in both platypuses and echidnas the receptors excited by cathodal (negative) pulses and inhibited by anodal (positive) pulses. Estimates give a total of 40,000 mucous sensory glands in the upper and lower bill of the platypus, whereas there are only about 100 in the tip of the echidna snout. Recording of electroreceptor-evoked activity from the brain of the platypus have shown that the largest area dedicated to somatosensory input from the bill, S1, shows alternating rows of mechanosensory and bimodal neurons. The bimodal neurons respond to both electrosensory and mechanical inputs. In skin of the platypus bill and echidna snout, apart from the electroreceptors, there are structures called push rods, which consist of a column of compacted cells that is able to move relatively independently of adjacent regions of skin. At the base of the column are Merkel cell complexes, known to be type I slowly adapting mechanoreceptors, and lamellated corpuscles, probably vibration receptors. It has been speculated that the platypus uses its electric sense to detect the electromyographic activity from moving prey in the water and for obstacle avoidance. Mechanoreceptors signal contact with the prey. For the echidna, a role for the electrosensory system has not yet been established during normal foraging behaviour, although it has been shown that it is able to detect the presence

  9. Coinheritance of hereditary spherocytosis and reversibility of cirrhosis in a young female patient with hereditary hemochromatosis

    Directory of Open Access Journals (Sweden)

    Höblinger A

    2009-04-01

    Full Text Available Abstract Here we report a 33-years-old woman with hereditary spherocytosis and hemochromatosis due to homozygosity for the C282Y mutation of the HFE gene. The coinheritance of both conditions led to severe iron overload and liver cirrhosis at young age. The patient was treated by repeated phlebotomy, and reversibility of cirrhosis was documented by transient elastography. This report discusses the pathophysiology of iron accumulation in patients with hemolytic anemia combined with HFE C282Y homozygosity. The case indicates that patients with hematological disorders characterized by increased erythropoetic activity should be screened for HFE mutations.

  10. 儿童遗传性肾脏疾病%Hereditary kidney diseases in children

    Institute of Scientific and Technical Information of China (English)

    张琰琴; 丁洁; 王芳; 张宏文

    2013-01-01

    About 10 to 15 percent of kidney diseases are inherited or related to genetic factors. While, hereditary kidney diseases have no specific clinical manifestations and react poorly to the therapy, as a result, about 30 percent of hospitalized children with chronic renal failure is due to hereditary kidney diseases in our country. Hereditary kidney diseases are related to many genes. Molecular genetic analysis plays an important role in the diagnosis and prenatal diagnosis of hereditary kidney diseases. Our group have made a series of research in hereditary kidney diseases for nearly 30 years. Here we review the research work and the main results in hereditary kidney diseases of our group.

  11. Sensory analysis of pet foods.

    Science.gov (United States)

    Koppel, Kadri

    2014-08-01

    Pet food palatability depends first and foremost on the pet and is related to the pet food sensory properties such as aroma, texture and flavor. Sensory analysis of pet foods may be conducted by humans via descriptive or hedonic analysis, pets via acceptance or preference tests, and through a number of instrumental analysis methods. Sensory analysis of pet foods provides additional information on reasons behind palatable and unpalatable foods as pets lack linguistic capabilities. Furthermore, sensory analysis may be combined with other types of information such as personality and environment factors to increase understanding of acceptable pet foods. Most pet food flavor research is proprietary and, thus, there are a limited number of publications available. Funding opportunities for pet food studies would increase research and publications and this would help raise public awareness of pet food related issues. This mini-review addresses current pet food sensory analysis literature and discusses future challenges and possibilities.

  12. The Evolution of Sensory Placodes

    Directory of Open Access Journals (Sweden)

    Francoise Mazet

    2006-01-01

    Full Text Available The vertebrate cranial sensory placodes are ectodermal embryonic patches that give rise to sensory receptor cells of the peripheral paired sense organs and to neurons in the cranial sensory ganglia. Their differentiation and the genetic pathways that underlay their development are now well understood. Their evolutionary history, however, has remained obscure. Recent molecular work, performed on close relatives of the vertebrates, demonstrated that some sensory placodes (namely the adenohypophysis, the olfactory, and accoustico-lateralis placodes first evolved at the base of the chordate lineage, while others might be specific to vertebrates. Combined with morphological and cellular fate data, these results also suggest that the sensory placodes of the ancestor of all chordates differentiated into a wide range of structures, most likely to fit the lifestyle and environment of each species.

  13. Sensory aspects of movement disorders.

    Science.gov (United States)

    Patel, Neepa; Jankovic, Joseph; Hallett, Mark

    2014-01-01

    Movement disorders, which include disorders such as Parkinson's disease, dystonia, Tourette's syndrome, restless legs syndrome, and akathisia, have traditionally been considered to be disorders of impaired motor control resulting predominantly from dysfunction of the basal ganglia. This notion has been revised largely because of increasing recognition of associated behavioural, psychiatric, autonomic, and other non-motor symptoms. The sensory aspects of movement disorders include intrinsic sensory abnormalities and the effects of external sensory input on the underlying motor abnormality. The basal ganglia, cerebellum, thalamus, and their connections, coupled with altered sensory input, seem to play a key part in abnormal sensorimotor integration. However, more investigation into the phenomenology and physiological basis of sensory abnormalities, and about the role of the basal ganglia, cerebellum, and related structures in somatosensory processing, and its effect on motor control, is needed.

  14. Growth and development: hereditary and mechanical modulations.

    Science.gov (United States)

    Mao, Jeremy J; Nah, Hyun-Duck

    2004-06-01

    Growth and development is the net result of environmental modulation of genetic inheritance. Mesenchymal cells differentiate into chondrogenic, osteogenic, and fibrogenic cells: the first 2 are chiefly responsible for endochondral ossification, and the last 2 for sutural growth. Cells are influenced by genes and environmental cues to migrate, proliferate, differentiate, and synthesize extracellular matrix in specific directions and magnitudes, ultimately resulting in macroscopic shapes such as the nose and the chin. Mechanical forces, the most studied environmental cues, readily modulate bone and cartilage growth. Recent experimental evidence demonstrates that cyclic forces evoke greater anabolic responses of not only craniofacial sutures, but also cranial base cartilage. Mechanical forces are transmitted as tissue-borne and cell-borne mechanical strain that in turn regulates gene expression, cell proliferation, differentiation, maturation, and matrix synthesis, the totality of which is growth and development. Thus, hereditary and mechanical modulations of growth and development share a common pathway via genes. Combined approaches using genetics, bioengineering, and quantitative biology are expected to bring new insight into growth and development, and might lead to innovative therapies for craniofacial skeletal dysplasia including malocclusion, dentofacial deformities, and craniofacial anomalies such as cleft palate and craniosynostosis, as well as disorders associated with the temporomandibular joint.

  15. Advances in laboratory diagnosis of hereditary spherocytosis.

    Science.gov (United States)

    Farias, Mariela Granero

    2016-11-12

    Among the red cell membrane disorders, hereditary spherocytosis (HS) is one of the most common causes of inherited hemolytic anemia. HS results from the deficiency or dysfunction of red blood cell membrane proteins, such as α spectrin, β spectrin, ankyrin, anion channel protein (Band-3 protein), protein 4.1 and protein 4.2. Conventionally, HS diagnosis is established through a series of tests, which include spherocytes identification in peripheral smear, reticulocyte count, osmotic fragility, etc. Currently, different hematological analyzers provide erythrocyte indicators that estimate the presence of spherocytes and correlate that with HS, which can be useful for disease screening. The most traditional method is the osmotic fragility (OF) test, which is labor-intensive and time-consuming to perform and presents low sensitivity and specificity values. Thus, new methods have been developed for HS diagnosis, such as flow cytometry. Current guidelines recommend the use of flow cytometry as a screening test for HS diagnosis using the eosin-5'-maleimide (EMA) binding test. Thus, HS diagnosis is the result of a collaboration between clinicians and laboratories, who should take into account the family history and the exclusion of other causes of secondary spherocytosis.

  16. Automated reticulocyte parameters for hereditary spherocytosis screening.

    Science.gov (United States)

    Lazarova, Elena; Pradier, Olivier; Cotton, Frédéric; Gulbis, Béatrice

    2014-11-01

    The laboratory diagnosis of hereditary spherocytosis (HS) is based on several screening and confirmatory tests; our algorithm includes clinical features, red blood cell morphology analysis and cryohaemolysis test, and, in case of positive screening, sodium dodecyl sulphate polyacrylamide gel electrophoresis as a diagnostic test. Using the UniCel DxH800 (Beckman Coulter) haematology analyser, we investigated automated reticulocyte parameters as HS screening tool, i.e. mean reticulocyte volume (MRV), immature reticulocyte fraction (IRF) and mean sphered cell volume (MSCV). A total of 410 samples were screened. Gel electrophoresis was applied to 159 samples that were positive for the screening tests. A total of 48 patients were diagnosed as HS, and seven were diagnosed as acquired autoimmune haemolytic anaemia (AIHA). Some other 31 anaemic conditions were also studied. From the receiver operating characteristic (ROC) curve analysis, both delta (mean cell volume (MCV)-MSCV) and MRV presented an area under the curve (AUC) of 0.98. At the diagnostic cut-off of 100 % sensitivity, MRV showed the best specificity of 88 % and a positive likelihood ratio of 8.7. The parameters IRF, MRV and MSCV discriminated HS not only from controls and other tested pathologies but also from AIHA contrary to the cryohaemolysis test. In conclusion, automated reticulocyte parameters might be helpful for haemolytic anaemia diagnostic orientation even for general laboratories. In combination with cryohaemolysis, they ensure an effective and time-saving screening for HS for more specialised laboratories.

  17. Multimodal Imaging in Hereditary Retinal Diseases

    Directory of Open Access Journals (Sweden)

    Francesco Pichi

    2013-01-01

    Full Text Available Introduction. In this retrospective study we evaluated the multimodal visualization of retinal genetic diseases to better understand their natural course. Material and Methods. We reviewed the charts of 70 consecutive patients with different genetic retinal pathologies who had previously undergone multimodal imaging analyses. Genomic DNA was extracted from peripheral blood and genotyped at the known locus for the different diseases. Results. The medical records of 3 families of a 4-generation pedigree affected by North Carolina macular dystrophy were reviewed. A total of 8 patients with Stargardt disease were evaluated for their two main defining clinical characteristics, yellow subretinal flecks and central atrophy. Nine male patients with a previous diagnosis of choroideremia and eleven female carriers were evaluated. Fourteen patients with Best vitelliform macular dystrophy and 6 family members with autosomal recessive bestrophinopathy were included. Seven patients with enhanced s-cone syndrome were ascertained. Lastly, we included 3 unrelated patients with fundus albipunctatus. Conclusions. In hereditary retinal diseases, clinical examination is often not sufficient for evaluating the patient’s condition. Retinal imaging then becomes important in making the diagnosis, in monitoring the progression of disease, and as a surrogate outcome measure of the efficacy of an intervention.

  18. Episodic neurological dysfunction in hereditary peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Girish Baburao Kulkarni

    2015-01-01

    Full Text Available Episodic transient neurological symptoms are an important set of problems presenting to a neurologist in his routine practice. Occasionally, detailed clinical history including past and family history supplemented with focused examination can bring out a rare cause for such symptoms. We describe in this report in a young male presenting with episodic focal neurological dysfunction, with family history of similar episodes in mother and brother. Examination showed features of pes cavus and peripheral neuropathy for which patient was asymptomatic. Mother and brother were established cases of hereditary neuropathy. Imaging on multiple occasions showed reversible white matter abnormalities. Clinical suspicion of X-linked Charcot-Marie-Tooth disease type 1 (CMT1X was confirmed with detection of mutation in Gap Junction B1 (GJB1 gene, which codes for connexin 32 protein (c.425G>A; p.R142Q hemizygous mutation. Though this mutation has been already reported in CMTX patients, it has not been associated with transient neurological dysfunctions. This is probably the first reported case of CMTX patient with transient neurological dysfunction from India, whose family members had similar episodes.

  19. Leber hereditary optic neuropathy: current perspectives.

    Science.gov (United States)

    Meyerson, Cherise; Van Stavern, Greg; McClelland, Collin

    2015-01-01

    Leber hereditary optic neuropathy (LHON) is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells.

  20. Pathogenesis of acidosis in hereditary fructose intolerance.

    Science.gov (United States)

    Richardson, R M; Little, J A; Patten, R L; Goldstein, M B; Halperin, M L

    1979-11-01

    An 18-yr-old man with a classical history of hereditary fructose intolerance (HFI) developed typical biochemical changes following an oral fructose load: fructosemia, hypoglycemia, hypophosphatemia, hyperuricemia, and metabolic acidosis. Hypokalemia (3.1 meq/liter) was also noted. Three aspects of this case expand the published literature on this syndrome: (1) Metabolic acidosis was found to be due to both lactic acidosis and proximal renal tubular acidosis (RTA). We could quantitate the relative contribution of each, and found that urinary bicarbonate loss due to proximal RTA accounted for less than 10% of the fall in serum bicarbonate. The major cause of the metabolic acidosis was lactic acidosis. (2) Hypokalemia was found to be due to movement of potassium out of the extracellular space rather than to urinary loss. Potassium may have entered cells with phosphate or may have been sequestered in the gastrointestinal tract. (3) The coexistence of proximal RTA and acidemia made it possible to study the effect of acidemia on the urine-blood partial pressure of carbon dioxide (PCO2) gradient in alkaline urine (U-B PCO2). The U-B PCO2 measured during acidemia was much higher at the same urine bicarbonate concentration than in normal controls during alkalemia, providing evidence in humans that acidemia stimulates distal nephron hydrogen-ion secretion.

  1. Leber hereditary optic neuropathy: current perspectives

    Science.gov (United States)

    Meyerson, Cherise; Van Stavern, Greg; McClelland, Collin

    2015-01-01

    Leber hereditary optic neuropathy (LHON) is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells. PMID:26170609

  2. [Designation criteria for Leber's hereditary optic neuropathy].

    Science.gov (United States)

    Nakamura, Makoto; Mimura, Osamu; Wakakura, Masato; Inatani, Masaru; Nakazawa, Toru; Shiraga, Fumio

    2015-05-01

    Designation criteria for Leber's hereditary optic neuropathy (LHON) have been established by a working group for retino-choroidal and optic atrophy funded by the Ministry of Health, Labor, and Welfare (MHLW) of Japan in collaboration with the Japanese Neuro-ophthalmology Society. The criteria are composed of three major symptoms and three ancillary test findings. According to the number and the combination of these symptoms and findings, subjects are classified into definite, probable, and possible LHON cases and asymptomatic carriers. The major symptoms include bilateral involvement with a time-lag, a papillomacular bundle atrophy, both characteristic optic disc findings at the acute phase. In the ancillary testings, mitochondrial DNA mutations specific for LHON are detailed with a table listing the mutation loci being attached. To enhance readers' understanding of description of the major symptoms and ancillary test findings, explanatory remarks on 11 parameters are supplemented. The establishment of the criteria facilitates epidemiological survey of LHON by MHLW and contributes to improvement of welfare for patients with LHON in Japan.

  3. [Hereditary sideroblastic anemia: a rare diagnosis].

    Science.gov (United States)

    Brahem-Jmili, N; Salem, N; Abdelkefi, S; Champ, B Grand; Bekri, S; Sboui, H; Mahjoub, T; Yacoub, S; Kortas, M

    2004-01-01

    Hereditary sideroblastic anemia is a very rare disease recessive and X-linked that affect heme biosynthesis by deficit or decreased of delta aminolevulinic acid synthase (ALAS) activity. We report a case of a six-month-old boy, admitted in the hospital for anemic syndrome. The hemogram showed anemia (hemoglobin: 4.5 g/dL), frankly hypochronic microcytic and a regenerated (mean corpuscular hemoglobin concentration: 26 g/dL, mean cell volume: 53 fl, reticulocytes: 10 x 10(9)/L) with red cells morphologic disorders in smears (anisopoikylocytosis) without attack of the other lineages; white blood cells: 11 x 10(9)/L (neutrophils: 64% and lymphocytes: 35%); platelets: 350 x 10(9)/L. Examination of bone marrow showed an important erythroid hyperplasia (about 69%) with dyserythropoiesis. Perls stain revealed intense siderosis with 90% of ringed sideroblasts and a large number of siderocytes. Exploration of ALAS2 and ABC7 genes on the DNA of the infant was not found abnormalities. Treatment with pyridoxine corrects moderately the anemia. By the way, we proposed to remind that iron deficiency, inflammatory syndrome and thalassemia are the common microcytic anemia. However, it's mandatory to explore other causes if diagnosis is not solved.

  4. Hypercoagulability in hereditary hemorrhagic telangiectasia with epilepsy

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2015-01-01

    Full Text Available Recent data indicate that in patients with hereditary hemorrhagic teleangiectasia (HHT, low iron levels due to inadequate replacement after hemorrhagic iron losses are associated with elevated factor-VIII plasma levels and consecutively increased risk of venous thrombo-embolism. Here, we report a patient with HHT, low iron levels, elevated factor-VIII, and recurrent venous thrombo-embolism. A 64-year-old multimorbid Serbian gipsy was diagnosed with HHT at age 62 years. He had a history of recurrent epistaxis, teleangiectasias on the lips, renal and pulmonary arterio-venous malformations, and a family history positive for HHT. He had experienced recurrent venous thrombosis (mesenteric vein thrombosis, portal venous thrombosis, deep venous thrombosis, insufficiently treated with phenprocoumon during 16 months and gastro-intestinal bleeding. Blood tests revealed sideropenia and elevated plasma levels of coagulation factor-VIII. His history was positive for diabetes, arterial hypertension, hyperlipidemia, smoking, cerebral abscess, recurrent ischemic stroke, recurrent ileus, peripheral arterial occluding disease, polyneuropathy, mild renal insufficiency, and epilepsy. Following recent findings, hypercoagulability was attributed to the sideropenia-induced elevation of coagulation factor-VIII. In conclusion, HHT may be associated with hypercoagulability due to elevated factor-VIII associated with low serum iron levels from recurrent bleeding. Iron substitution may prevent HHT patients from hypercoagulability.

  5. Hereditary pancreatitis and secondary screening for early pancreatic cancer.

    Science.gov (United States)

    Vitone, L J; Greenhalf, W; Howes, N R; Neoptolemos, J P

    2005-01-01

    Hereditary pancreatitis is an autosomal dominant disease with incomplete penetrance (80%), accounting for approximately 1% of all cases of pancreatitis. It is characterized by the onset of recurrent attacks of acute pancreatitis in childhood and frequent progression to chronic pancreatitis. Whitcomb et al. identified the cationic trypsinogen gene (PRSS1) on chromosome 7q35 as the site of the mutation that causes hereditary pancreatitis. The European registry of hereditary pancreatitis and familial pancreatic cancer (EUROPAC) aims to identify and make provisions for those affected by hereditary pancreatitis and familial pancreatic cancer. The most common mutations in hereditary pancreatitis are R122H, N29I and A16V but many families have been described with clinically defined hereditary pancreatitis where there is no PRSS1 mutation. It is known that the cumulative lifetime risk (to age 70 years) of pancreatic cancer is 40% in individuals with hereditary pancreatitis. This subset of individuals form an ideal group for the development of a screening programme aimed at detecting pancreatic cancer at an early stage in an attempt to improve the presently poor long-term survival. Current screening strategies involve multimodality imaging (computed tomography, endoluminal ultrasound) and endoscopic retrograde cholangiopancreatography for pancreatic juice collection followed by molecular analysis of the DNA extracted from the juice. The potential benefit of screening (curative resection) must be balanced against the associated morbidity and mortality of surgery. Philosophically, the individual's best interest must be sought in light of the latest advances in medicine and science following discussions with a multidisciplinary team in specialist pancreatic centres.

  6. Hereditary Spherocytosis and Hereditary Elliptocytosis: Aberrant Protein Sorting during Erythroblast Enucleation

    Energy Technology Data Exchange (ETDEWEB)

    Salomao, Marcela; Chen, Ke; Villalobos, Jonathan; Mohandas, Narla; An, Xiuli; Chasis, Joel Anne

    2010-02-08

    During erythroblast enucleation, membrane proteins distribute between extruded nuclei and reticulocytes. In hereditary spherocytosis (HS) and hereditary elliptocytosis (HE), deficiencies of membrane proteins, in addition to those encoded by the mutant gene, occur. Elliptocytes, resulting from protein 4.1R gene mutations, lack not only 4.1R but also glycophorin C, which links the cytoskeleton and bilayer. In HS resulting from ankyrin-1 mutations, band 3, Rh-associated antigen, and glycophorin A are deficient. The current study was undertaken to explore whether aberrant protein sorting, during enucleation, creates these membrane-spanning protein deficiencies. We found that although glycophorin C sorts to reticulocytes normally, it distributes to nuclei in 4.1R-deficient HE cells. Further, glycophorin A and Rh-associated antigen, which normally partition predominantly to reticulocytes, distribute to both nuclei and reticulocytes in an ankyrin-1-deficient murine model of HS. We conclude that aberrant protein sorting is one mechanistic basis for protein deficiencies in HE and HS.

  7. [Hereditary pathology of the enamel and dentin. A review of molecular genetic research].

    Science.gov (United States)

    Beliakov, Iu A; Elizarova, V M; Krotov, V A; Blinnikova, O E

    2000-01-01

    Mapped phenotype of imperfect amelogenesis, type II imperfect dentinogenesis, hereditary opalescent dentin, Capdepont's dysplasia, and type II dentin dysplasia is described for the first time in Russia. Classification of hereditary disorders in dentin development is presented.

  8. Chapter 22: Hereditary and acquired angioedema.

    Science.gov (United States)

    Georgy, Mary S; Pongracic, Jacqueline A

    2012-01-01

    Hereditary angioedema (HAE) is an autosomal dominant disorder defined by a deficiency of functional C1 esterase inhibitor (C1-INH). Acquired angioedema (AAE) is caused by either consumption (type 1) or inactivation (type 2) of CI-INH. Both HAE and AAE can be life-threatening. The screening test for both conditions is complement component C4, which is low to absent at times of angioedema or during quiescent periods. A useful test to differentiate HAE from AAE is C1q protein, which is normal in HAE and low in AAE. There are three types of HAE: type 1 HAE is most common, occurring in ∼85% of patients and characterized by decreased production of C1-INH, resulting in reduced functional activity to 5-30% of normal. In type 2, which occurs in 15% of cases, C1-INH is detectable in normal or elevated quantities but is dysfunctional. Finally, type 3, which is rare and almost exclusively occurs in women, is estrogen dependent and associated with normal CI-INH and C4 levels. One-third of these patients have a gain-of-function mutation in clotting factor XII leading to kallikrein-driven bradykinin production. Although the anabolic steroid, danazol, is useful in increasing the concentration of C4 and reducing the episodes of angioedema in HAE and AAE, it has expected adverse effects. Fortunately, disease-specific therapies are available and include C1-INH enzyme for i.v. infusion either acutely or empirically, ecallantide, an inhibitor of kallikrein, and icatibant, a bradykinin B2-receptor antagonist, both approved for acute angioedema and administered, subcutaneously.

  9. Use of ecallantide in pediatric hereditary angioedema.

    Science.gov (United States)

    MacGinnitie, Andrew J; Davis-Lorton, Mark; Stolz, Leslie E; Tachdjian, Raffi

    2013-08-01

    Hereditary angioedema (HAE) due to C1-inhibitor deficiency is a rare autosomal dominant disease that manifests as sudden unpredictable attacks of subcutaneous or submucosal edema affecting the skin, intestine, and upper airway. Ecallantide is a plasma kallikrein inhibitor indicated for treatment of HAE attacks in patients aged 16 years and older. This analysis examines safety and efficacy of ecallantide for treatment of HAE attacks in patients <18 years of age. Data for patients aged 9 to 17 years treated subcutaneously with 30 mg ecallantide or placebo were pooled from 4 clinical studies (2 double-blind, placebo-controlled and 2 open-label). Efficacy end points included 2 HAE-specific patient-reported outcome measures: mean symptom complex severity (MSCS) score and treatment outcome score (TOS). Times to initial improvement, sustained improvement, and complete or near-complete symptom resolution were calculated. Treatment-emergent adverse events were examined. Overall, 29 pediatric patients were included; 25 of them received ecallantide for 62 total HAE attacks, and 10 received placebo for 10 total attacks. Ecallantide-treated attacks revealed clinically relevant reduction in symptom severity at 4 hours postdosing based on mean change in MSCS score (-1.4 ± 0.9 ecallantide versus -0.9 ± 0.6 placebo) and TOS (73.9 ± 35.50 ecallantide versus 45.0 ± 43.78 placebo). Patients treated with ecallantide showed rapid improvement in symptoms (median time to complete or near-complete symptom resolution: 181 minutes). No serious adverse events related to treatment were observed. Ecallantide appears effective for HAE attacks in adolescents, with rapid symptom improvement. No unexpected safety issues were identified.

  10. Outcomes of Lensectomy in Hereditary Lens Subluxation

    Directory of Open Access Journals (Sweden)

    Mohammad-Hossein Dehghan

    2008-12-01

    Full Text Available

    PURPOSE: To evaluate the results of pars plana lensectomy in patients with hereditary lens subluxation. METHOD: Hospital records of patients with hereditary lens subluxation who had undergone pars plana lensectomy at Labbafinejad Medical Center, Tehran-Iran from 1996 to 2003 were reviewed. Patients with more than 6 months of follow up were included. Underlying disorders, best corrected visual acuity (BCVA before and after surgery, intraocular pressure (IOP, postoperative refraction and complications were evaluated. RESULTS: Overall, records of 87 eyes of 49 patients including 27 male and 22 female subjects were reviewed. Mean follow up duration was 20±18 months. Underlying disorders leading to lens subluxation included Marfan syndrome (79.5%, Weill-Marchesani syndrome (8.2%, simple ectopia lentis (8.2%, and homocystinuria (4.1%. The most common indication for surgery was non-correctable refractive error (92.1%. Mean BCVA was 1.13 LogMAR (20/250 preoperatively, which improved to 0.26 LogMAR (20/30-20/40 postoperatively (P < 0.001. BCVA better than 20/40 was achieved in 82.8% of cases after surgery. Angle-supported anterior chamber intraocular lens (ACIOL was implanted in

  11. Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders.

    Science.gov (United States)

    Da Costa, Lydie; Galimand, Julie; Fenneteau, Odile; Mohandas, Narla

    2013-07-01

    Hereditary spherocytosis and elliptocytosis are the two most common inherited red cell membrane disorders resulting from mutations in genes encoding various red cell membrane and skeletal proteins. Red cell membrane, a composite structure composed of lipid bilayer linked to spectrin-based membrane skeleton is responsible for the unique features of flexibility and mechanical stability of the cell. Defects in various proteins involved in linking the lipid bilayer to membrane skeleton result in loss in membrane cohesion leading to surface area loss and hereditary spherocytosis while defects in proteins involved in lateral interactions of the spectrin-based skeleton lead to decreased mechanical stability, membrane fragmentation and hereditary elliptocytosis. The disease severity is primarily dependent on the extent of membrane surface area loss. Both these diseases can be readily diagnosed by various laboratory approaches that include red blood cell cytology, flow cytometry, ektacytometry, electrophoresis of the red cell membrane proteins, and mutational analysis of gene encoding red cell membrane proteins.

  12. A Case of hereditary spherocytosis coexisting with Gilbert's syndrome.

    Science.gov (United States)

    Lee, Min Jae; Chang, Yoon Hwan; Kang, Seung Hwa; Mun, Se Kwon; Kim, Heyjin; Han, Chul Ju; Kim, Jin; Kang, Hye Jin

    2013-03-25

    We recently encountered a case of hereditary spherocytosis coexisting with Gilbert's syndrome. Patient was initially diagnosed with Gilbert's syndrome and observed, but other findings suggestive of concurrent hemolysis, such as splenomegaly and gallstones were noted during the follow-up period. Therefore, further evaluations, including a peripheral blood smear, osmotic fragility test, autohemolysis test, and red blood cell membrane protein test were performed, and coexisting hereditary spherocytosis was diagnosed. Genotyping of the conjugation enzyme uridine diphosphate-glucuronosyltransferase was used to confirm Gilbert's syndrome. Because of the high prevalence rates and similar symptoms of these 2 diseases, hereditary spherocytosis can be masked in patients with Gilbert's syndrome. In review of a case and other article, the possibility of the coexistence of these 2 diseases should be considered, especially in patients with unconjugated hyperbilirubinemia who also have splenomegaly and gallstones.

  13. Anaesthetic management of a patient with hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Nergis Ataol

    2015-12-01

    Full Text Available Hereditary angioedema is a rare autosomal dominant disorder caused by reduced activity of the C1 esterase inhibitor. Patients with hereditary angioedema are clinically characterized by recurrent episodes of swelling of the extremities, face, trunk, airways and abdominal organs. Attacks may occur either spontaneously or following trauma, stress, surgery, infections and hormonal fluctuations. The most common cause of death is asphyxia related to laryngeal edema. Giving C1 esterase inhibitor is the most effective method of treatment. Also fresh frozen plasma, androgen steroids, quinine pathway inhibitors, antifibrinolytics and bradykinin receptor antagonists can be used as treatment. In this paper, the anesthetic management of a patient with hereditary angioedema undergoing inguinal hernia repair surgery is reported.

  14. Neuromyelitis optica antibody in Leber hereditary optic neuropathy: case report

    Directory of Open Access Journals (Sweden)

    Luciano Mesquita Simão

    2012-08-01

    Full Text Available Neuromyelitis optica antibody (or aquaporin-4 antibody is a well stablished serum marker associated to high-risk neuromyelitis optica syndrome that presents as an inflammatory demyelinating disease characterized by the occurrence of bilateral and simultaneous optic neuritis without complete visual recovery or it occurs as an isolated episode of transverse myelitis accompanied by longitudinally extensive spinal cord lesions. On the other hand, Leber hereditary optic neuropathy is a primarily hereditary disorder that affects all tissues of the body and its clinical presentation is tissue-specific for the optic nerve and, eventually, it might reach the spinal cord. Overlapping clinical features of neuromyelitis optica and Leber hereditary optic neuropathy may suggest common target organ diseases. The case report described herein emphasizes the coexistence of serum markers of both diseases, and suggests that further investigation of this challenging clinical presentation is warranted to confirm or rule out this association.

  15. Neuromyelitis optica antibody in Leber hereditary optic neuropathy: case report.

    Science.gov (United States)

    Simão, Luciano Mesquita

    2012-01-01

    Neuromyelitis optica antibody (or aquaporin-4 antibody) is a well established serum marker associated to high-risk neuromyelitis optica syndrome that presents as an inflammatory demyelinating disease characterized by the occurrence of bilateral and simultaneous optic neuritis without complete visual recovery or it occurs as an isolated episode of transverse myelitis accompanied by longitudinally extensive spinal cord lesions. On the other hand, Leber hereditary optic neuropathy is a primarily hereditary disorder that affects all tissues of the body and its clinical presentation is tissue-specific for the optic nerve and, eventually, it might reach the spinal cord. Overlapping clinical features of neuromyelitis optica and Leber hereditary optic neuropathy may suggest common target organ diseases. The case report described herein emphasizes the coexistence of serum markers of both diseases, and suggests that further investigation of this challenging clinical presentation is warranted to confirm or rule out this association.

  16. Characteristic modules and tensor products over quasi-hereditary algebras

    Institute of Scientific and Technical Information of China (English)

    Yue-hui ZHANG; Shi-ying SHEN; Ping-kai YE

    2007-01-01

    Let A be a monomial quasi-hereditary algebra with a pure strong exact Borel subalgebra B. It is proved that the category of induced good modules over B is contained in the category of good modules over A; that the characteristic module of A is an induced module of that of B via the exact functor - (×)B A if and only if the induced A-module of an injective B-module remains injective as a B-module. Moreover, it is shown that an exact Borel subalgebra of a basic quasi-hereditary serial algebra is right serial and that the characteristic module of a basic quasi-hereditary serial algebra is exactly the induced module of that of its exact Borel subalgebra.

  17. Characteristic modules and tensor products over quasi-hereditary algebras

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Let A be a monomial quasi-hereditary algebra with a pure strong exact Borel subalgebra B.It is proved that the category of induced good modules over B is contained in the category of good modules over A;that the characteristic module of A is an induced module of that of B via the exact functor-(?)_B A if and only if the induced A-module of an injective B-module remains injective as a B-module.Moreover,it is shown that an exact Borel subalgebra of a basic quasi-hereditary serial algebra is right serial and that the characteristic module of a basic quasi-hereditary serial algebra is exactly the induced module of that of its exact Borel subalgebra.

  18. Hereditary stomatocytosis: First case report from Valley of Kashmir

    Directory of Open Access Journals (Sweden)

    Javid Rasool

    2015-01-01

    Full Text Available Stomatocytes are erythrocytes with a central slit or mouth-shaped (stoma area of central pallor when examined on dried smears. In wet preparations, they are uniconcave rather than biconcave, giving them a bowllike appearance. In vitro, stomatocytes are produced by drugs that intercalate into the inner half of the lipid bilayer, thereby expanding the inner lipid surface area relative to that of the outer half of the bilayer. Hereditary stomatocytosis (also known as hereditary hydrocytosis, or overhydrated stomatocytosis refers to a heterogeneous group of autosomal dominant hemolytic anemias caused by altered sodium permeability of the red cell membrane. We present the first case report of hereditary stomatocytosis in a 10-year-old male from the valley of Kashmir. Only eight families with this condition have been described worldwide.

  19. Principally Left Hereditary and Principally Left Strong Radicals

    Institute of Scientific and Technical Information of China (English)

    S. Tumurbat; R. Wiegandt

    2001-01-01

    A radical γ is normal if and only if γ is principally left hereditary and principally left strong (i.e., γ(L) = L e A and Lz ∈γ for all z ∈ L imply L γ(A)). Let a radical γ satisfy that A°∈γ and S° A° imply S°∈γ.Then γ is a hereditary normal radical if and only if γ is principally left strong and γ {A | (A, +,◇a) ∈γ a ∈ A}, where the multiplication ◇a is defined by x ◇a y = xay. The Behrens radical class B is the largest principally left hereditary subclass of the Brown-McCoy radical class G. Neither3 nor G is principally left strong.

  20. Cellular nanoscale sensory wave computing

    CERN Document Server

    Baatar, Chagaan; Roska, Tamas

    2010-01-01

    This fresh perspective of sensory computing successfully bridges the gap between nanoscale devices and CMOS integrated circuits. Practical and complex algorithms are also discussed, in addition to new developments like the nanoscale antenna.

  1. [The significance of Goodpasture antigen in hereditary nephritis].

    Science.gov (United States)

    Basta-Jovanović, Gordana; Radojević-Skodrić, Sanja; Jovanović, Milena; Bogdanović, Ljiljana; Bogdanović, Radovan; Lezaić, Visnja; Nesić, Vidosava; Dikman, Steven

    2008-12-01

    Two types of hereditary nephritis, nonprogressive and progressive, clinically present as asymptomatic haematuria, sometimes combined with proteinuria. At the onset, in both types, light microscopic changes are minimal, immunofluorescence findings are negative, and diagnosis can be made only upon electron microscopic findings that are considered to be specific. The aim of this study was to determine the significance of Goodpasture antigen detection in diagnosis of progressive and nonprogressive hereditary nephritis in its early phase. Analysis of renal biopsy specimens was done in patients with hereditary nephritis that were followed from 1990 to 2005. Progression of renal disease was examined in 14 patients with Alport's syndrome, 10 patients with thin basement membrane disease, and 6 patients with unclassified hereditary nephritis diagnosed. For all these cases, indirect immunofluorescence study with serum from a patient with high titer of Goodpasture autoantibodies that recognize the antigenic determinants in human glomerular and tubular basement membrane was performed. In 11 out of 14 cases diagnosed as Alport's syndrome, there was negative staining with Goodpasture serum, and in 3 additional cases with Alport's syndrome, expression of Goodpasture antigen in glomerular basement membrane and thin basement membrane was highly reduced. In all 10 patients with thin basement membrane disease, immunofluorescence showed intensive, bright linear staining with Goodpasture serum along glomerular and tubular basement membrane. In 2 out of 6 patients with unclassified hereditary nephritis, Goodpasture antigen expression was very strong, in one patient it was very reduced, and in 3 patients it was negative. The results of our study show that Goodpasture antigen detection plays a very important role in differential diagnosis of progressive and nonpregressive hereditary nephritis, particularly in early phases of the disease.

  2. Analyzing sensory data with R

    CERN Document Server

    Le, Sebastien

    2014-01-01

    Quantitative Descriptive Approaches When panelists rate products according to one single list of attributes Data, sensory issues, notations In practice For experienced users: Measuring the impact of the experimental design on the perception of the products? When products are rated according to one single list of attributesData, sensory issues, notations In practice For experienced users: Adding supplementary information to the product space When products are rated according to several lists

  3. Spinal sensory circuits in motion

    OpenAIRE

    2016-01-01

    International audience; The role of sensory feedback in shaping locomotion has been long debated. Recent advances in genetics and behavior analysis revealed the importance of proprioceptive pathways in spinal circuits. The mechanisms underlying peripheral mechanosensation enabled to unravel the networks that feedback to spinal circuits in order to modulate locomotion. Sensory inputs to the vertebrate spinal cord were long thought to originate from the periphery. Recent studies challenge this ...

  4. Sensory Topography of Oral Structures.

    Science.gov (United States)

    Bearelly, Shethal; Cheung, Steven W

    2017-01-01

    Sensory function in the oral cavity and oropharynx is integral to effective deglutition and speech production. The main hurdle to evaluation of tactile consequences of upper aerodigestive tract diseases and treatments is access to a reliable clinical tool. We propose a rapid and reliable procedure to determine tactile thresholds using buckling monofilaments to advance care. To develop novel sensory testing monofilaments and map tactile thresholds of oral cavity and oropharyngeal structures. A prospective cross-sectional study of 37 healthy adults (12 men, 25 women), specifically without a medical history of head and neck surgery, radiation, or chemotherapy, was carried out in an academic tertiary medical center to capture normative data on tactile sensory function in oral structures. Cheung-Bearelly monofilaments were constructed by securing nylon monofilament sutures (2-0 through 9-0) in the lumen of 5-French ureteral catheters, exposing 20 mm for tapping action. Buckling force consistency was evaluated for 3 lots of each suture size. Sensory thresholds of 4 oral cavity and 2 oropharyngeal subsites in healthy participants (n = 37) were determined by classical signal detection methodology (d-prime ≥1). In 21 participants, test-retest reliability of sensory thresholds was evaluated. Separately in 16 participants, sensory thresholds determined by a modified staircase method were cross-validated with those obtained by classical signal detection. Buckling forces of successive suture sizes were distinct (P sensory threshold determination was high (Cronbach α, >0.7). The lower lip, anterior tongue, and buccal mucosa were more sensitive than the soft palate, posterior tongue, and posterior pharyngeal wall (P Threshold determination by classical signal detection and modified staircase methods were highly correlated (r = 0.93, P sensory function assessment of oral cavity and oropharyngeal structures.

  5. Sensory Dissonance Using Memory Model

    DEFF Research Database (Denmark)

    Jensen, Karl Kristoffer

    2015-01-01

    Music may occur concurrently or in temporal sequences. Current machine-based methods for the estimation of qualities of the music are unable to take into account the influence of temporal context. A method for calculating dissonance from audio, called sensory dissonance is improved by the use...... of a memory model. This approach is validated here by the comparison of the sensory dissonance using memory model to data obtained using human subjects....

  6. Intragenic Duplication A Novel Mutational Mechanism in Hereditary Pancreatitis

    DEFF Research Database (Denmark)

    Joergensen, M. T.; Geisz, A.; Brusgaard, K.

    2011-01-01

    OBJECTIVES: In a hereditary pancreatitis family from Denmark, we identified a novel intragenic duplication of 9 nucleotides in exon-2 of the human cationic trypsinogen (PRSS1) gene (c.63_71dup) which at the amino-acid level resulted in the insertion of 3 amino acids within the activation peptide...... pancreatitis. The accelerated activation of p.K23_I24insIDK by cathepsin B is a unique biochemical property not found in any other pancreatitis-associated trypsinogen mutant. In contrast, the robust autoactivation of the novel mutant confirms the notion that increased autoactivation is a disease......-relevant mechanism in hereditary pancreatitis....

  7. Hereditary Gigantism-the biblical giant Goliath and his brothers.

    Science.gov (United States)

    Donnelly, Deirdre E; Morrison, Patrick J

    2014-05-01

    The biblical giant Goliath has an identifiable family tree suggestive of autosomal dominant inheritance. We suggest that he had a hereditary pituitary disorder possibly due to the AIP gene, causing early onset and familial acromegaly or gigantism. We comment on the evidence within the scriptures for his other relatives including a relative with six digits and speculate on possible causes of the six digits. Recognition of a hereditary pituitary disorder in the biblical Goliath and his family sheds additional information on his and other family members' battles with David and his relatives.

  8. Mutator gene and hereditary non-polyposis colorectal cancer

    Science.gov (United States)

    de la Chapelle, Albert; Vogelstein, Bert; Kinzler, Kenneth W.

    2008-02-05

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

  9. Diagnostic evaluation of hereditary hemochromatosis (HFE and non-HFE).

    Science.gov (United States)

    Bardou-Jacquet, Edouard; Brissot, Pierre

    2014-08-01

    The management and understanding of hereditary hemochromatosis have evolved with recent advances in iron biology and the associated discovery of numerous genes involved in iron metabolism. HFE-related (type 1) hemochromatosis remains the most frequent form, characterized by C282Y mutation homozygosity. Rare forms of hereditary hemochromatosis include type 2 (A and B, juvenile hemochromatosis caused by HJV and HAMP mutation), type 3 (related to TFR2 mutation), and type 4 (A and B, ferroportin disease). The diagnostic evaluation relies on comprehension of the involved pathophysiologic defect, and careful characterization of the phenotype, which gives clues to guide appropriate genetic testing.

  10. Hereditary benign telangiectasia without family history in China

    Institute of Scientific and Technical Information of China (English)

    CAI Lin; SUN Qing-miao; ZANG Dong-jie; ZHANG Jian-zhong

    2011-01-01

    A case of hereditary benign telangiectasia without family history was reported. A 39-year-old woman presented with small and tiny telangiectases on the face, neck, upper trunk and forearms at birth. The numbers and sizes of the lesions increased gradually and she had no hemorrhagic diathesis and systemic diseases. No similar patients were found in her family. Upon physical examination, telangiectases were found on the face, neck, upper trunk and forearms; and a telangiectatic erythema was found on the right forearm 25 mm ×40 mm in size. Histopathology examination showed a normal epidermis and dilation of the capillaries at upper dermis. Hereditary benign telangiectasia without family history was diagnosed.

  11. [Hereditary hemachromatosis: clinical case report and literature review].

    Science.gov (United States)

    Prochazka, Ricardo; Tagle, Martín

    2006-01-01

    Hemachromatosis is a hereditary condition, producing progressive iron overload as a result of the mutation in proteins that regulate intestinal iron absorption. It is a systemic disease with several manifestations including cirrhosis, diabetes mellitus, cardiomyopathy, joint disease and a proportion of asymptomatic patients. When it is diagnosed and treatment with phlebotomies is initiated before any organ damage is developed, the prognosis is very good, with normal survival free of manifestations. This condition is common in European populations. We report the case of a Peruvian patient of European ancestry who is asymptomatic, but has high levels of aminotransferases and elevated iron markers. Genetic testing confirmed the patient's diagnosis of hereditary hemachromatosis.

  12. The molecular basis of hereditary fructose intolerance in Italian children.

    Science.gov (United States)

    Santamaria, R; Scarano, M I; Esposito, G; Chiandetti, L; Izzo, P; Salvatore, F

    1993-10-01

    We investigated the molecular defects of the aldolase B gene in five unrelated patients affected by hereditary fructose intolerance. The techniques used were DNA amplification, direct sequencing and allele-specific oligonucleotide (ASO) hybridization. The most frequent substitutions found in the hereditary fructose intolerance alleles analysed were the A174D and the A149P mutations, which account for 50% and 30% of the alleles, respectively. In two unrelated families, we found a rare mutation, the MD delta 4 previously described only in one British family, which may be an important cause of the disease in Italy.

  13. The optic nerve head in hereditary optic neuropathies.

    Science.gov (United States)

    O'Neill, Evelyn C; Mackey, David A; Connell, Paul P; Hewitt, Alex W; Danesh-Meyer, Helen V; Crowston, Jonathan G

    2009-05-01

    Hereditary optic neuropathies are a prominent cause of blindness in both children and adults. The disorders in this group share many overlapping clinical characteristics, including morphological changes that occur at the optic nerve head. Accurate and prompt clinical diagnosis, supplemented with imaging when indicated, is essential for optimum management of the relevant optic neuropathy and appropriate counseling of the patient on its natural history. Patient history, visual field assessment, optic disc findings and imaging are the cornerstones of a correct diagnosis. This Review highlights the characteristic optic nerve head features that are common to the various hereditary optic neuropathies, and describes the features that enable the conditions to be differentiated.

  14. [Pathogenic Genes of A Hereditary Hemorrhagic Telangiectasia Pedigree].

    Science.gov (United States)

    Cheng, Xiao-Hui; Tu, Chuan-Qing; Sun, Shun-Chang; Li, Jan-Yun; Zhang, Xu-Yan; Wang, Dian-Wen; Huang, Can

    2015-08-01

    To identify the mutation of ENG and ALK1 genes in a hereditary hemorrhagic telangiectasia pedigree. 14 exons of ENG gene and 9 exons of ALK1 gene in 11 menbers of this pedigree 4 generation were amplified by reverse transcription-polymerase chain reaction (RT-PCR), the PCR products were screened by direct sequencing. A nonsense mutation c.447G > A was found in exon 4 of ENG gen of the pedigreee, resulting in change of Trp 149 into Stop, while no gene mutation was found in ALK1 gene. The hereditary hemorrhagic telangiectasia in this pedigree is caused by the nonsense mutation c.447G > A in ENG gene.

  15. A novel point mutation in PMP22 gene in an Italian family with hereditary neuropathy with liability to pressure palsies.

    Science.gov (United States)

    Muglia, Maria; Patitucci, Alessandra; Rizzi, Romana; Ungaro, Carmine; Conforti, Francesca Luisa; Gabriele, Anna Lia; Magariello, Angela; Mazzei, Rosalucia; Motti, Luisa; Sabadini, Rossella; Sprovieri, Teresa; Marcello, Norina; Quattrone, Aldo

    2007-12-15

    Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant inherited disorder characterized by recurrent sensory or motor dysfunction. In 85% of HNPP cases the genetic defect is a 1.4 Mb deletion on chromosome 17p11.2, encompassing the PMP22 gene. Point mutations in the PMP22 gene responsible for HNPP phenotypes are rare. We investigated a 17-years-old girl who led to our detecting a novel mutation in PMP22 gene. The mutation was also detected in her father and corresponded to a deletion of one tymidine at position 11 in exon2 (c.11delT). This novel mutation creates a shift on the reading frame starting at codon 4 and leads to the introduction of a premature stop at codon 6.

  16. Ultrasound pattern sum score, homogeneity score and regional nerve enlargement index for differentiation of demyelinating inflammatory and hereditary neuropathies.

    Science.gov (United States)

    Grimm, Alexander; Vittore, Debora; Schubert, Victoria; Lipski, Christina; Heiling, Bianka; Décard, Bernhard F; Axer, Hubertus

    2016-07-01

    To investigate the use of nerve ultrasound in the differentiation between Charcot-Marie Tooth hereditary neuropathy (CMT1) and chronic inflammatory demyelinating polyradiculoneuropathies (CIDP), multifocal motor neuropathy (MMN) and multifocal acquired demyelinating sensory and motor neuropathies (MADSAM). Ultrasound/electrophysiology of predefined nerves was performed in CMT1a/b, immunoneuropathies, and healthy controls. Ultrasound pattern sum score (UPSS, sum of the amount of 12 predefined measurement points), homogeneity score (HS) and regional nerve enlargement index (RNEI) in ulnar, median, and tibial nerve were used for evaluation of morphology. 13 CMT1, 27 CIDP, 10 MADSAM, 12 MMN, and 23 controls were included. Significant enlargement was shown in all neuropathies compared to the controls, (pneuropathies by the use of boundary values. By the use of quantitative scores, ultrasound differentiation of demyelinating neuropathies is operationalized and ameliorated compared to CSA measurements only. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Two Cases of Elderly-Onset Hereditary Neuropathy with Liability to Pressure Palsy Manifesting Bilateral Peroneal Nerve Palsies

    Directory of Open Access Journals (Sweden)

    Norihiko Kawaguchi

    2012-10-01

    Full Text Available Hereditary neuropathy with liability to pressure palsy (HNPP is characterized by recurrent focal neuropathies, which usually become symptomatic in the second or third decade of life. However, clinical phenotypic heterogeneity among patients with HNPP has recently been reported. Certain patients show polyneuropathy-type diffuse nerve injuries, whereas others remain asymptomatic at older ages. We present two cases of elderly-onset bilateral peroneal nerve palsies with diffuse muscle weakness in the lower limbs and glove-and-stocking type sensory disturbance. Both patients were diagnosed with HNPP by genetic analyses that detected deletions of chromosome 17p11.2 in peripheral myelin protein 22 genes. Their clinical courses suggested that the Japanese sitting style termed ‘seiza’, a way of sitting on the floor with the lower legs crossed under the thighs, was a precipitating factor for the bilateral peroneal nerve palsies.

  18. An Introduction to Intelligent Sensory Evaluation

    Institute of Scientific and Technical Information of China (English)

    曾宪奕; 丁永生

    2004-01-01

    Sensory evaluation is the evaluation of signals that a buman receives via its sensory organs. Nowadays sensory evaluation is widely used in quality inspection and quality control of products. and many other fields. Actually sensory evaluation always give. uncertain and inprecise results, therefore it derivates many problems. we reviews in detail these problem and give some cumputing methods to resolve them.

  19. The diagnosis of hereditary fructose intolerance.

    Science.gov (United States)

    Steinmann, B; Gitzelmann, R

    1981-09-01

    Hereditary fructose intolerance (HFI) is a potentially life-threatening disorder and can be suspected from a detailed nutritional history. The usefulness of 2 diagnostic procedures, fructose tolerance test (FTT) and aldolase assay on biopsied liver, was studied. A standardized intravenous FTT with 200 mg/kg b.w. was done on 11 children with HFI, 17 age-matched contrast children, 6 adults with HFI and 6 adult controls. Blood glucose, phosphorus, urate, magnesium and fructose were followed for 2 hours. By the FTT, each HFI individual was reliably distinguished from controls and contrasts and even from those with acute liver disease other than HFI. Both children with non-HFI hepatopathy examined by both procedures had a normal FTT in spite of reduced liver fructaldolase activity. HFI children responded to the FTT by earlier and more pronounced hypoglycemia than adults, and one girl converted to an adult type response between the ages 12 and 181/2 years. Responses of two HFI sibling pairs and of one set of monozygotic twins were typical for age, but resemblance was no greater than within the unrelated HFI probands. The intravenous FTT is judged a reliable diagnostic tool, simple and harmless if done in hospital. Essential fructosuria is readily diagnosed by the FTT, but fructose-1,6-diphosphatase deficiency and HFI are not differentiated with certainty. Liver biopsies were obtained from 35 children with HFI, 14 contrast persons and 10 controls (of which 9 organ donors) and examined enzymatically. Deficiency of fructaldolase was observed in all HFI children but also in some contrast children suffering from acute liver disease other than HFI. In these, HFI could only be excluded when the reduced activity of reference enzymes such as fructose-1,6-diphosphatase and glucose-6-phosphatase and liver histology were included in the evaluation. In one deceased HFI infant, fructaldolase was deficient in both, liver and kidney cortex. Extent of antibody activation and of heat

  20. Topological Structures and Membrane Nanostructures of Erythrocytes after Splenectomy in Hereditary Spherocytosis Patients via Atomic Force Microscopy

    OpenAIRE

    Li, Ying; Lu, Liyuan; Li, Juan

    2016-01-01

    Hereditary spherocytosis is an inherited red blood cell membrane disorder resulting from mutations of genes encoding erythrocyte membrane and cytoskeletal proteins. Few equipments can observe the structural characteristics of hereditary spherocytosis directly expect for atomic force microscopy In our study, we proved atomic force microscopy is a powerful and sensitive instrument to describe the characteristics of hereditary spherocytosis. Erythrocytes from hereditary spherocytosis patients we...

  1. Study of glycolytic intermediates in hereditary elliptocytosis with thalassemia

    Directory of Open Access Journals (Sweden)

    Pavri Roshan

    1977-01-01

    Full Text Available Glycolytic intermediates like ATP, DPG and GSH have been studied in a family with. hereditary elliptocytosis and thalassemia. Results indicate a fall in ATP with a concomitant rise in DPG in the Patient. Findings are discussed in relation to other data.

  2. Non-recurrent SEPT9 duplications cause hereditary neuralgic amyotrophy.

    NARCIS (Netherlands)

    Collie, A.M.; Landsverk, M.L.; Ruzzo, E.; Mefford, H.C.; Buysse, K.; Adkins, J.R.; Knutzen, D.M.; Barnett, K.; Brown Jr., R.H.; Parry, G.J.; Yum, S.W.; Simpson, D.A.; Olney, R.K.; Chinnery, P.F.; Eichler, E.E.; Chance, P.F.; Hannibal, M.C.

    2010-01-01

    BACKGROUND: Genomic copy number variants have been shown to be responsible for multiple genetic diseases. Recently, a duplication in septin 9 (SEPT9) was shown to be causal for hereditary neuralgic amyotrophy (HNA), an episodic peripheral neuropathy with autosomal dominant inheritance. This duplicat

  3. Hereditary spherocytosis diagnosed with the eosin-5'-maleimide binding test.

    Science.gov (United States)

    Watanabe, Toru; Ono, Hiroyuki; Tajima, Iwao; Ishigaki, Hidetoshi; Hakamata, Akio; Shirai, Masami; Endoh, Akira; Hongo, Teruaki

    2014-06-01

    We describe three cases of hereditary spherocytosis (HS) diagnosed using the eosin-5'-maleimide (EMA) binding test and discuss the relevance of the EMA binding test. In Japan, this test is not widely used because the prevalence of HS is low. This test is a valuable screening test for the diagnosis of HS.

  4. Mitochondrial processes are impaired in hereditary inclusion body myopathy.

    NARCIS (Netherlands)

    Eisenberg, I.; Novershtern, N.; Itzhaki, Z.; Becker-Cohen, M.; Sadeh, M.; Willems, P.H.G.M.; Friedman, N.; Koopman, W.J.H.; Mitrani-Rosenbaum, S.

    2008-01-01

    Hereditary inclusion body myopathy (HIBM) is an adult onset, slowly progressive distal and proximal myopathy. Although the causing gene, GNE, encodes for a key enzyme in the biosynthesis of sialic acid, its primary function in HIBM remains unknown. To elucidate the pathological mechanisms leading fr

  5. Leber's hereditary optic neuropathy and vitamin B12 deficiency

    NARCIS (Netherlands)

    Pott, Jan Willem R.; Wong, Kwok H.

    2006-01-01

    Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON. Methods: A case series was observed. Results: Three pa

  6. Leber's hereditary optic neuropathy: case report and literature review

    Directory of Open Access Journals (Sweden)

    Hélio Afonso Ghizoni Teive

    Full Text Available CONTEXT: Leber's hereditary optic neuropathy is an important cause of progressive painless visual loss among young male patients. OBJECTIVE: To report on a case of a young patient with a clinical and neurophysiological condition suggestive of Leber's hereditary optic neuropathy, confirmed by genetic testing. CASE REPORT: We describe a 17-year-old male with progressive bilateral visual loss. Two maternal uncles had had similar patterns of visual loss. The patient had a history of smoking and alcohol abuse. Neuro-ophthalmological examination revealed visual acuity of 20/800 in both eyes, with decreased direct and consensual pupillary light reflexes. Fundus examination demonstrated pale optic discs. The visual evoked potential test showed signs of conduction disturbances in both optic nerves and campimetric study showed complete visual loss in all fields of both eyes. A diagnosis of bilateral optic neuropathy with a clinical suspicion of Leber's hereditary optic neuropathy was made. A blood sample was submitted to genetic analysis in relation to the principal mutations of this disorder, and homoplasmic mutation in 11778 was detected, thereby confirming the diagnosis of Leber's hereditary optic neuropathy.

  7. Gene-environment interactions in Leber hereditary optic neuropathy

    NARCIS (Netherlands)

    M.A. Kirkman; P. Yu-Wai-Man (Patrick); A. Korsten (Alex); M. Leonhardt (Miriam); K. Dimitriadis (Konstantin); I.F.M. de Coo (René); T. Klopstock (Thomas); P.F. Chinnery

    2009-01-01

    textabstractLeber hereditary optic neuropathy (LHON) is a genetic disorder primarily due to mutations of mitochondrial DNA (mtDNA). Environmental factors are thought to precipitate the visual failure and explain the marked incomplete penetrance of LHON, but previous small studies have failed to conf

  8. On the many faces of Leber hereditary optic neuropathy

    NARCIS (Netherlands)

    Oostra, RJ; Tijmes, NT; Cobben, JM; Bolhuis, PA; vanNesselrooij, BPM; Houtman, WA; deKokNazaruk, MM; BleekerWagemakers, EM

    1997-01-01

    Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder, associated with mutations in the mitochondrial DNA, which is notorious for its aspecific presentations. Two pedigrees are described with cases that are atypical for LHON with respect to sex, age of onset, interval between t

  9. Hereditary Angioedema Attacks : Local Swelling at Multiple Sites

    NARCIS (Netherlands)

    Hofman, Zonne L M; Relan, Anurag; Hack, C. Erik

    2016-01-01

    Hereditary angioedema (HAE) patients experience recurrent local swelling in various parts of the body including painful swelling of the intestine and life-threatening laryngeal oedema. Most HAE literature is about attacks located in one anatomical site, though it is mentioned that HAE attacks may al

  10. On the many faces of Leber hereditary optic neuropathy

    NARCIS (Netherlands)

    Oostra, RJ; Tijmes, NT; Cobben, JM; Bolhuis, PA; vanNesselrooij, BPM; Houtman, WA; deKokNazaruk, MM; BleekerWagemakers, EM

    Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder, associated with mutations in the mitochondrial DNA, which is notorious for its aspecific presentations. Two pedigrees are described with cases that are atypical for LHON with respect to sex, age of onset, interval between

  11. Intragenic duplication: a novel mutational mechanism in hereditary pancreatitis

    DEFF Research Database (Denmark)

    Joergensen, Maiken T; Geisz, Andrea; Brusgaard, Klaus

    2011-01-01

    In a hereditary pancreatitis family from Denmark, we identified a novel intragenic duplication of 9 nucleotides in exon-2 of the human cationic trypsinogen (PRSS1) gene (c.63_71dup) which at the amino-acid level resulted in the insertion of 3 amino acids within the activation peptide of cationic...

  12. Sulindac treatment in hereditary non-pollyposis colorectal cancer

    NARCIS (Netherlands)

    Rijcken, Fleur E. M.; Hollema, Harry; van der Zee, Ate G. J.; van der Sluis, Tineke; Ek, Wytske Boersma-van; Kleibeuker, Jan H.

    2007-01-01

    Non-steroidal anti-inflammatory drugs, e.g. sulindac have been extensively studied for chemoprevention in familial adenomatous polyposis, but not in hereditary non-polyposis colorectal cancer (HNPCC). We evaluated these effects in HNPCC using surrogate end-points for cancer risk. In a randomised dou

  13. Allelic imbalance in hereditary and sporadic prostate cancer.

    NARCIS (Netherlands)

    Verhage, B.; Houwelingen, K.P. van; Ruijter, T.E.G.; Kiemeney, L.A.L.M.; Schalken, J.A.

    2003-01-01

    BACKGROUND: In this study, we evaluate the pattern of allelic imbalance (AI) in both sporadic prostate cancer (SPC) and hereditary prostate cancer (HPC) at loci that frequently show allelic imbalance in sporadic prostate cancer, or are believed to have a putative role in the disease. METHODS: DNA ob

  14. Longitudinal Cerebral Blood Flow Changes during Speech in Hereditary Ataxia

    Science.gov (United States)

    Sidtis, John J.; Strother, Stephen C.; Naoum, Ansam; Rottenberg, David A.; Gomez, Christopher

    2010-01-01

    The hereditary ataxias constitute a group of degenerative diseases that progress over years or decades. With principal pathology involving the cerebellum, dysarthria is an early feature of many of the ataxias. Positron emission tomography was used to study regional cerebral blood flow changes during speech production over a 21 month period in a…

  15. Keratinocytes modify fibroblast metabolism in hereditary gingival fibromatosis.

    NARCIS (Netherlands)

    Meng, L.; Ye, X.; Fan, M.; Xiong, X.; Hoff, J.W. Von den; Bian, Z.

    2008-01-01

    OBJECTIVES: Hereditary gingival fibromatosis (HGF) is a rare benign disorder characterized by progressive fibrous overgrowth of the gingiva. The proliferation and expression of growth factors of HGF keratinocytes are abnormal. However, the exact role of keratinocytes in HGF pathogenesis is still unk

  16. The Almost Split Sequences for Trivial Extensions of Hereditary Algebras

    Institute of Scientific and Technical Information of China (English)

    Zhang Yu-lin; Yao Hai-lou

    2014-01-01

    Let A be a basic hereditary artin algebra and R=AnQ be the trivial extension of A by its minimal injective cogenerator Q. We construct some right (left) almost split morphisms and irreducible morphisms in modR through the correspond-ing morphisms in modA. Furthermore, we can determine its almost split sequences in modR.

  17. Hereditary spastic paraplegia caused by the PLP1 'rumpshaker mutation'

    DEFF Research Database (Denmark)

    Svenstrup, Kirsten; Giraud, Geneviève; Boespflug-Tanguy, Odile

    2010-01-01

    BACKGROUND: Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterised by progressive spasticity and weakness in the lower limbs. Mutations in PLP1 on the X chromosome cause spastic paraplegia type 2 (SPG2) or the allelic...

  18. Prognostic Factors for Distress After Genetic Testing for Hereditary Cancer

    NARCIS (Netherlands)

    Voorwinden, Jan S; Jaspers, Jan P C

    2015-01-01

    The psychological impact of an unfavorable genetic test result for counselees at risk for hereditary cancer seems to be limited: only 10-20 % of counselees have psychological problems after testing positive for a known familial mutation. The objective of this study was to find prognostic factors tha

  19. Visual Rehabilitation of Persons with Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Rudanko, S.-L.

    1995-01-01

    This article presents results of a noncontrolled clinical study of 20 persons with Leber's hereditary optic neuropathy who were treated from 1976 to 1990 at the Low Vision Centre of the Finnish Federation of the Visually Handicapped. The importance of early functional visual rehabilitation is emphasized, as is the use of low vision aids to help…

  20. Hereditary fructose intolerance and alpha(1) antitrypsin deficiency.

    Science.gov (United States)

    Hillebrand, G; Schneppenheim, R; Oldigs, H D; Santer, R

    2000-07-01

    A patient with coexisting hereditary fructose intolerance (HFI) and alpha(1) antitrypsin deficiency (alpha(1)ATD) is described. Protease inhibitor typing was not conclusive, presumably because of impaired N-glycosylation secondary to HFI. The case underlines the diagnostic role of molecular genetic techniques in inborn errors of metabolism.

  1. Leber's hereditary optic neuropathy and vitamin B12 deficiency

    NARCIS (Netherlands)

    Pott, Jan Willem R.; Wong, Kwok H.

    2006-01-01

    Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON. Methods: A case series was observed. Results: Three

  2. Hereditary orotic aciduria with epilepsy and without megaloblastic anemia.

    Science.gov (United States)

    Grohmann, Karina; Lauffer, Heinz; Lauenstein, Peter; Hoffmann, Georg F; Seidlitz, Günter

    2015-04-01

    Hereditary orotic aciduria is a rare metabolic disease that results from a defect of uridine-5-monophosphate synthase (UMPS). In affected patients, main clinical symptoms are a markedly increased urinary excretion of orotic acid combined with megaloblastic anemia. This report describes a new case of UMPS deficiency without megaloblastic anemia but with epilepsy. Georg Thieme Verlag KG Stuttgart · New York.

  3. Systemic treatment for hereditary cancers: a 2012 update.

    Science.gov (United States)

    Imyanitov, Evgeny N; Byrski, Tomasz

    2013-04-01

    The history of specific therapy for hereditary tumors dates back to mid 1980s and involves a number of reports demonstrating regression of familial colon polyps upon administration of sulindac. Virtually no clinical studies on other hereditary cancer types were available until the year 2009, when Byrski et al. presented the data on unprecedented sensitivity of BRCA1-associated breast malignancies to cisplatin. This breakthrough has revived interest to the treatment of cancer in germ-line mutation carriers. Recent trials and clinical observations have confirmed the efficacy of platinating agents and PARP inhibitors in BRCA1/2-driven breast, ovarian and pancreatic carcinomas. Pegylated liposomal doxorubicin may be considered as a promising treatment option for BRCA1/2-related ovarian cancer after the failure of platinum-containing therapy. Several novel drugs have been recently introduced in the management of rare familial tumor syndromes. Vandetanib, a low-molecular weight RET kinase inhibitor, demonstrated substantial efficacy in the treatment of hereditary and sporadic medullary thyroid cancer. Vismodegib, an inhibitor of SMO oncoprotein, caused regression of basal-cell carcinomas in patients with Gorlin syndrome. Down-regulation of mTOR kinase by everolimus has been successfully used for the therapy of subependymal giant-cell astrocytomas in patients with tuberous sclerosis. The achievements in the prevention, diagnostics and treatment of hereditary cancers may serve as an excellent example of triumph of translational medicine.

  4. Prognostic Factors for Distress After Genetic Testing for Hereditary Cancer

    NARCIS (Netherlands)

    Voorwinden, Jan S.; Jaspers, Jan P C

    2016-01-01

    The psychological impact of an unfavorable genetic test result for counselees at risk for hereditary cancer seems to be limited: only 10-20 % of counselees have psychological problems after testing positive for a known familial mutation. The objective of this study was to find prognostic factors tha

  5. Longitudinal Cerebral Blood Flow Changes during Speech in Hereditary Ataxia

    Science.gov (United States)

    Sidtis, John J.; Strother, Stephen C.; Naoum, Ansam; Rottenberg, David A.; Gomez, Christopher

    2010-01-01

    The hereditary ataxias constitute a group of degenerative diseases that progress over years or decades. With principal pathology involving the cerebellum, dysarthria is an early feature of many of the ataxias. Positron emission tomography was used to study regional cerebral blood flow changes during speech production over a 21 month period in a…

  6. Motor activation in SPG4-linked hereditary spastic paraplegia

    DEFF Research Database (Denmark)

    Scheuer, KH; Nielsen, JE; Krabbe, Katja

    2006-01-01

    OBJECTIVE: The aim of this study was to investigate the extent of motor cortical functional reorganisation in patients with SPG4-linked hereditary spastic paraplegia by exploring cortical motor activation related to movements of clinically affected (lower) and unaffected (upper) limbs. METHODS...

  7. Hereditary Ovarian Cancer: Not Only BRCA 1 and 2 Genes

    Directory of Open Access Journals (Sweden)

    Angela Toss

    2015-01-01

    Full Text Available More than one-fifth of ovarian tumors have hereditary susceptibility and, in about 65–85% of these cases, the genetic abnormality is a germline mutation in BRCA genes. Nevertheless, several other suppressor genes and oncogenes have been associated with hereditary ovarian cancers, including the mismatch repair (MMR genes in Lynch syndrome, the tumor suppressor gene, TP53, in the Li-Fraumeni syndrome, and several other genes involved in the double-strand breaks repair system, such as CHEK2, RAD51, BRIP1, and PALB2. The study of genetic discriminators and deregulated pathways involved in hereditary ovarian syndromes is relevant for the future development of molecular diagnostic strategies and targeted therapeutic approaches. The recent development and implementation of next-generation sequencing technologies have provided the opportunity to simultaneously analyze multiple cancer susceptibility genes, reduce the delay and costs, and optimize the molecular diagnosis of hereditary tumors. Particularly, the identification of mutations in ovarian cancer susceptibility genes in healthy women may result in a more personalized cancer risk management with tailored clinical and radiological surveillance, chemopreventive approaches, and/or prophylactic surgeries. On the other hand, for ovarian cancer patients, the identification of mutations may provide potential targets for biologic agents and guide treatment decision-making.

  8. Alterations of red blood cell metabolome in overhydrated hereditary stomatocytosis.

    NARCIS (Netherlands)

    Darghouth, D.; Koehl, B.; Heilier, J.F.; Madalinski, G.; Bovee, P.H.; Bosman, G.J.C.G.M.; Delaunay, J.; Junot, C.; Romeo, P.H.

    2011-01-01

    Overhydrated hereditary stomatocytosis, clinically characterized by hemolytic anemia, is a rare disorder of the erythrocyte membrane permeability to monovalent cations, associated with mutations in the Rh-associated glycoprotein gene. We assessed the red blood cell metabolome of 4 patients with this

  9. Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Kjeldsen, J

    2000-01-01

    Gastrointestinal bleeding occurs in a number of patients with hereditary hemorrhagic telangiectasia (HHT) and may lead to a high transfusion need. The aim of this study was to estimate the occurrence and severity of gastrointestinal bleeding in a geographically well defined HHT population....

  10. Treatment for dysphagia (swallowing difficulties) in hereditary ataxia.

    Science.gov (United States)

    Vogel, Adam P; Keage, Megan J; Johansson, Kerstin; Schalling, Ellika

    2015-11-13

    Hereditary ataxias are a heterogeneous group of disorders resulting in progressive inco-ordination. Swallowing impairment, also known as dysphagia, is a common and potentially life threatening sequel of disease progression. The incidence and nature of dysphagia in these conditions is largely unknown. The loss of an effective and safe swallow can dramatically affect the health and well-being of an individual. Remediation of difficulties of eating and drinking is an important goal in the clinical care of people with hereditary ataxia. To assess the effects of interventions for swallowing impairment (dysphagia) in people with hereditary ataxias. We searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL Plus, PsycINFO, and the Education Resources Information Center (ERIC) on 14 September 2015. We also searched Linguistics and Language Behavior Abstracts (LLBA), Dissertation Abstracts, and Trials Registries on 24 September 2015. We considered all randomised controlled trials (RCTs) and quasi-RCTs that compared treatments for hereditary ataxia with placebo or no treatment. We only included studies measuring dysphagia. Three review authors (ES, KJ, MK) independently screened all titles and abstracts. In the event of any disagreement or uncertainty over the inclusion of a particular paper, the review authors planned to meet and reach consensus. We identified no RCTs from the 519 titles and abstracts screened. We excluded papers primarily for not including participants with a hereditary ataxia (that is, being focused on other neurological conditions), being theoretical reviews rather than intervention studies, or being neither randomised nor quasi-randomised trials.We identified five papers of various design that described treatment for dysphagia, or improvement to swallow as a by-product of treatment, in people with hereditary ataxia. None of these studies were RCTs or

  11. Sensory Transduction in Caenorhabditis elegans

    Science.gov (United States)

    Brown, Austin L.; Ramot, Daniel; Goodman, Miriam B.

    The roundworm Caenorhabditis elegans has a well-defined and comparatively simple repertoire of sensory-guided behaviors, all of which rely on its ability to detect chemical, mechanical or thermal stimuli. In this chapter, we review what is known about the ion channels that mediate sensation in this remarkable model organism. Genetic screens for mutants defective in sensory-guided behaviors have identified genes encoding channel proteins, which are likely transducers of chemical, thermal, and mechanical stimuli. Such classical genetic approaches are now being coupled with molecular genetics and in vivo cellular physiology to elucidate how these channels are activated in specific sensory neurons. The ion channel superfamilies implicated in sensory transduction in C. elegans - CNG, TRP, and DEG/ENaC - are conserved across phyla and also appear to contribute to sensory transduction in other organisms, including vertebrates. What we learn about the role of these ion channels in C. elegans sensation is likely to illuminate analogous processes in other animals, including humans.

  12. Hereditary neuropathy with liability to pressure palsy: an investigation in a rare and large Chinese family.

    Science.gov (United States)

    He, Yuan; Wu, Qiang; Xu, Zhipeng; Wang, Qianqian; Wang, Weili; Li, Dezhong; Liu, Wanhong; He, Xiaohua

    2012-01-01

    Hereditary neuropathy with liability to pressure palsy (HNPP), mainly associated with the peripheral myelin protein 22 (PMP22) gene, is generally an autosomal-dominant inherited peripheral neuropathy. The present large family including four generations provides an exciting opportunity to gain important insights into HNPP in China. A large 43-member family with ten members suspected to be affected by HNPP was studied. Neurologic examinations, electrophysiological and neuropathological studies and molecular genetic testing were used for these kindred. Clinically, the proband had limb hyposthenia and atrophy, and his mother showed declined tendon reflexes in the right lower limb. Electrophysiologically, sensory and motor nerve conduction velocities were generalized reduced. Sural nerve biopsy for the proband showed focal thickesning of the myelin sheaths. Furthermore, real-time quantitative PCR demonstrated that the PMP22 gene has a higher Ct value than reference gene in all suspected patients. These results indicated that the family is indeed a rare and large pedigree of HNPP caused by the deletion of PMP22 gene. Given that the suspected patient in the fourth generation is absent, this family is still worthy of further follow-up study. Copyright © 2012 S. Karger AG, Basel.

  13. Hereditary neuropathy with liability to pressure palsies in childhood: Case series and literature update.

    Science.gov (United States)

    Chrestian, Nicolas; McMillan, Hugh; Poulin, Chantal; Campbell, Craig; Vajsar, Jiri

    2015-09-01

    Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) is a rare condition in childhood with a diverse range of clinical presentations. We analyzed the clinical presentation and electrophysiological data of 12 children with a confirmed PMP22 gene deletion and reviewed the published reports of HNPP in children and compared our data with the reports from the literature review. Peroneal palsy was the most common presentation (42%) followed by brachial plexus palsy in 25% of our cases. Nerve conduction studies were always suggestive of the diagnosis demonstrating 3 major patterns: multifocal demyelination at the area of entrapment, generalized sensory-motor polyneuropathy and a combination of the two first patterns in a vast majority (60%). Surprisingly, there was bilateral or unilateral electrophysiological entrapment of the median nerve at the carpal tunnel in all our patients. The clinical presentation of HNPP in childhood is heterogeneous and electrophysiological findings are helpful in establishing the diagnosis. Any unexplained mononeuropathy or multifocal neuropathy should lead to PMP22 gene testing to look for the deletion. Early diagnosis is important in order to facilitate appropriate genetic counseling and also for the appropriate care for these patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Molecular genetics and mechanisms of disease in distal hereditary motor neuropathies: insights directing future genetic studies.

    Science.gov (United States)

    Drew, A P; Blair, I P; Nicholson, G A

    2011-11-01

    The distal hereditary motor neuropathies (dHMNs) are a clinically and genetically heterogeneous group of disorders that primarily affect motor neurons, without significant sensory involvement. New dHMN genes continue to be identified. There are now 11 causative genes described for dHMN, and an additional five genetic loci with unidentified genes. This genetic heterogeneity has further delineated the classification of dHMN, which was previously classified according to mode of inheritance, age at onset, and additional complicating features. Some overlap between phenotypically distinct forms of dHMN is also apparent. The mutated genes identified to-date in dHMN include HSPB1, HSPB8, HSPB3, DCTN1, GARS, PLEKHG5, BSCL2, SETX, IGHMBP2, ATP7A and TRPV4. The pathogenesis of mutations remains to be fully elucidated, however common pathogenic mechanisms are emerging. These include disruption of axonal transport, RNA processing defects, protein aggregation and inclusion body formation, disrupted calcium channel activity, and loss of neuroprotective signalling. Some of these dHMN genes are also mutated in Charcot-Marie-Tooth (CMT) disease and spinal muscular atrophy (SMA). This review examines the growing number of identified dHMN genes, discusses recent insights into the functions of these genes and possible pathogenic mechanisms, and looks at the increasing overlap between dHMN and the other neuropathies CMT2 and SMA.

  15. Oestrogens ameliorate mitochondrial dysfunction in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Giordano, Carla; Montopoli, Monica; Perli, Elena; Orlandi, Maurizia; Fantin, Marianna; Ross-Cisneros, Fred N; Caparrotta, Laura; Martinuzzi, Andrea; Ragazzi, Eugenio; Ghelli, Anna; Sadun, Alfredo A; d'Amati, Giulia; Carelli, Valerio

    2011-01-01

    Leber's hereditary optic neuropathy, the most frequent mitochondrial disease due to mitochondrial DNA point mutations in complex I, is characterized by the selective degeneration of retinal ganglion cells, leading to optic atrophy and loss of central vision prevalently in young males. The current study investigated the reasons for the higher prevalence of Leber's hereditary optic neuropathy in males, exploring the potential compensatory effects of oestrogens on mutant cell metabolism. Control and Leber's hereditary optic neuropathy osteosarcoma-derived cybrids (11778/ND4, 3460/ND1 and 14484/ND6) were grown in glucose or glucose-free, galactose-supplemented medium. After having shown the nuclear and mitochondrial localization of oestrogen receptors in cybrids, experiments were carried out by adding 100 nM of 17β-oestradiol. In a set of experiments, cells were pre-incubated with the oestrogen receptor antagonist ICI 182780. Leber's hereditary optic neuropathy cybrids in galactose medium presented overproduction of reactive oxygen species, which led to decrease in mitochondrial membrane potential, increased apoptotic rate, loss of cell viability and hyper-fragmented mitochondrial morphology compared with control cybrids. Treatment with 17β-oestradiol significantly rescued these pathological features and led to the activation of the antioxidant enzyme superoxide dismutase 2. In addition, 17β-oestradiol induced a general activation of mitochondrial biogenesis and a small although significant improvement in energetic competence. All these effects were oestrogen receptor mediated. Finally, we showed that the oestrogen receptor β localizes to the mitochondrial network of human retinal ganglion cells. Our results strongly support a metabolic basis for the unexplained male prevalence in Leber's hereditary optic neuropathy and hold promises for a therapeutic use for oestrogen-like molecules.

  16. Red blood cell vesiculation in hereditary hemolytic anemia

    Science.gov (United States)

    Alaarg, Amr; Schiffelers, Raymond M.; van Solinge, Wouter W.; van Wijk, Richard

    2013-01-01

    Hereditary hemolytic anemia encompasses a heterogeneous group of anemias characterized by decreased red blood cell survival because of inherited membrane, enzyme, or hemoglobin disorders. Affected red blood cells are more fragile, less deformable, and more susceptible to shear stress and oxidative damage, and show increased vesiculation. Red blood cells, as essentially all cells, constitutively release phospholipid extracellular vesicles in vivo and in vitro in a process known as vesiculation. These extracellular vesicles comprise a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they originate from multi-vesicular bodies, or as microvesicles when formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules that are implicated in intercellular communication and in different biological and pathophysiological processes. Mature red blood cells release in principle only microvesicles. In hereditary hemolytic anemias, the underlying molecular defect affects and determines red blood cell vesiculation, resulting in shedding microvesicles of different compositions and concentrations. Despite extensive research into red blood cell biochemistry and physiology, little is known about red cell deformability and vesiculation in hereditary hemolytic anemias, and the associated pathophysiological role is incompletely assessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with focus on red blood cell vesiculation. Also, we review recent scientific findings on the molecular defects of hereditary hemolytic anemias, and their correlation with red blood cell deformability and vesiculation. Integrating bio-analytical findings on abnormalities of red blood cells and their microvesicles will be critical for a better understanding of the pathophysiology of hereditary hemolytic anemias. PMID

  17. Red blood cell vesiculation in hereditary hemolytic anemia

    Directory of Open Access Journals (Sweden)

    Amr eAlaarg

    2013-12-01

    Full Text Available Hereditary hemolytic anemia encompasses a heterogeneous group of anemias characterised by decreased red blood cell survival because of inherited membrane, enzyme, or hemoglobin disorders. Affected red blood cells are more fragile, less deformable, and more susceptible to shear stress and oxidative damage, and show increased vesiculation. Red blood cells, as essentially all cells, constitutively release phospholipid extracellular vesicles in vivo and in vitro in a process known as vesiculation. These extracellular vesicles comprise a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they originate from multi-vesicular bodies, or as microvesicles when formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules that are implicated in intercellular communication and in different biological and pathophysiological processes. Mature red blood cells release in principle only microvesicles. In hereditary hemolytic anemias, the underlying molecular defect affects and determines red blood cell vesiculation, resulting in shedding microvesicles of different compositions and concentrations. Despite extensive research into red blood cell biochemistry and physiology, little is known about red cell deformability and vesiculation in hereditary hemolytic anemias, and the associated pathophysiological role is incompletely asessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with focus on red blood cell vesiculation. Also, we review recent scientific findings on the molecular defects of hereditary hemolytic anemias, and their correlation with red blood cell deformability and vesiculation. Integrating bio-analytical findings on abnormalities of red blood cells and their microvesicles will be critical for a better understanding of the pathophysiology of hereditary

  18. Red blood cell vesiculation in hereditary hemolytic anemia.

    Science.gov (United States)

    Alaarg, Amr; Schiffelers, Raymond M; van Solinge, Wouter W; van Wijk, Richard

    2013-12-13

    Hereditary hemolytic anemia encompasses a heterogeneous group of anemias characterized by decreased red blood cell survival because of inherited membrane, enzyme, or hemoglobin disorders. Affected red blood cells are more fragile, less deformable, and more susceptible to shear stress and oxidative damage, and show increased vesiculation. Red blood cells, as essentially all cells, constitutively release phospholipid extracellular vesicles in vivo and in vitro in a process known as vesiculation. These extracellular vesicles comprise a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they originate from multi-vesicular bodies, or as microvesicles when formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules that are implicated in intercellular communication and in different biological and pathophysiological processes. Mature red blood cells release in principle only microvesicles. In hereditary hemolytic anemias, the underlying molecular defect affects and determines red blood cell vesiculation, resulting in shedding microvesicles of different compositions and concentrations. Despite extensive research into red blood cell biochemistry and physiology, little is known about red cell deformability and vesiculation in hereditary hemolytic anemias, and the associated pathophysiological role is incompletely assessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with focus on red blood cell vesiculation. Also, we review recent scientific findings on the molecular defects of hereditary hemolytic anemias, and their correlation with red blood cell deformability and vesiculation. Integrating bio-analytical findings on abnormalities of red blood cells and their microvesicles will be critical for a better understanding of the pathophysiology of hereditary hemolytic anemias.

  19. Sensory analysis in grapes benitaka

    Energy Technology Data Exchange (ETDEWEB)

    Santillo, Amanda G.; Rodrigues, Flavio T.; Arthur, Paula B.; Villavicencio, Ana Lucia C.H. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Abstract Sensory analysis is considered one of the main techniques when you want to know the organoleptic qualities of foods. Marketing strategies, showing that some foods produced organically is more nutritious, flavorful than conventional ones are affecting some consumers. The advantages of using radiation in sensory analysis are not the formation of waste, the less nutritional loss and little change in taste of food. The possibility that the fruit is harvested at more advanced maturity, when all characteristics of flavor and external appearance are fully developed is another advantage. The possibility of fruits being packed irradiated prevents contamination after processing. This type of study, ionizing radiation associated with sensory evaluation scarce, making it necessary for future discoveries. The objective this paper was to evaluate the quality of grapes Benitaka after the irradiation process with doses 0,5; 1; 1,5 e 2 kGy. (author)

  20. Sensory nerve conduction studies in neuralgic amyotrophy.

    Science.gov (United States)

    van Alfen, Nens; Huisman, Willem J; Overeem, S; van Engelen, B G M; Zwarts, M J

    2009-11-01

    Neuralgic amyotrophy is a painful, episodic peripheral nerve disorder localized to the brachial plexus. Sensory symptoms occur in 80% of the patients. We assessed the frequency of abnormalities in sensory nerve conduction studies of the lateral and medial antebrachial cutaneous, radial sensory, median sensory, and ulnar sensory nerves in 112 patients. Sensory nerve conduction studies showed abnormalities in nerves, even when the nerve was clinically affected. The lateral and medial antebrachial cutaneous nerves were most often abnormal, in 15% and 17% of nerves. No correlation with the presence or localization of clinical deficits was found. Brachial plexus sensory nerve conduction studies seem to be of little diagnostic value in neuralgic amyotrophy. Our findings also indicate that some sensory lesions may be in the nerve roots instead of the plexus. An examination of normal sensory nerve conduction studies does not preclude neuralgic amyotrophy as a diagnosis.

  1. Role of detection of microsatellite instability in Chinese with hereditary nonpolyposis colorectal cancer or ordinary hereditary colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Wen-Zhi Liu; Feng Jin; Zhen-Hai Zhang; Shu-Bao Wang

    2006-01-01

    AIM: To detect microsatellite instability (MSI) in patients with hereditary nonpolyposis colorectal cancer or ordinary hereditary colorectal cancer and to provide criteria for screening the kindreds with hereditary nonpolyposis colorectal cancer at molecular level.METHODS: MSI was detected in the specimens from 20 cases with HNPCC, 20 cases with ordinary hereditary colorectal cancer and 20 cases with sporadic colorectal cancer by means of polymerase chain reaction-single strand conformation polymorphism.RESULTS: The positive rate of MSI was 85% (17/20) in HNPCC group, 40% (8/20) in ordinary hereditary colorectal cancer group and 10% (2/20) in the sporadic colorectal cancer group respectively. The differences were significant. The mean ages of the three groups were 43.6, 52.2, and 61.8 years respectively, which increased gradually. The incidence of right hemicolon cancer was 64.7%, 37.5%, and 0% respectively, which decreased gradually and had significant difference. The expression ratio of BAT26 and BAT25 was 94.1% respectively, which was highest in the 5 gene sites studied. The incidence of poorly differentiated adenocarcinoma was 70.6% in HNPCC group among high frequency microsatellite instability (MSI-H), which was higher than the other two groups, which had 50% and 50% respectively.CONCLUSION: The incidence of MSI-H is higher in HNPCC group. The detection of MSI is simple and economical and has high correlation with the clinicopathologic feature of HNPCC and can be used as a screening method to detect the germ line mutation of the mismatch repair gene.

  2. New treatments addressing the pathophysiology of hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Davis Alvin E

    2008-04-01

    Full Text Available Abstract Hereditary angioedema is a serious medical condition caused by a deficiency of C1-inhibitor. The condition is the result of a defect in the gene controlling the synthesis of C1-inhibitor, which regulates the activity of a number of plasma cascade systems. Although the prevalence of hereditary angioedema is low – between 1:10,000 to 1:50,000 – the condition can result in considerable pain, debilitation, reduced quality of life, and even death in those afflicted. Hereditary angioedema presents clinically as cutaneous swelling of the extremities, face, genitals, and trunk, or painful swelling of the gastrointestinal mucosa. Angioedema of the upper airways is extremely serious and has resulted in death by asphyxiation. Subnormal levels of C1-inhibitor are associated with the inappropriate activation of a number of pathways – including, in particular, the complement and contact systems, and to some extent, the fibrinolysis and coagulation systems. Current findings indicate bradykinin, a product of contact system activation, as the primary mediator of angioedema in patients with C1-inhibitor deficiency. However, other systems may play a role in bradykinin's rapid and excessive generation by depleting available levels of C1-inhibitor. There are currently no effective therapies in the United States to treat acute attacks of hereditary angioedema, and currently available agents used to treat hereditary angioedema prophylactically are suboptimal. Five new agents are, however, in Phase III development. Three of these agents replace C1-inhibitor, directly addressing the underlying cause of hereditary angioedema and re-establishing regulatory control of all pathways and proteases involved in its pathogenesis. These agents include a nano-filtered C1-inhibitor replacement therapy, a pasteurized C1-inhibitor, and a recombinant C1-inhibitor isolated from the milk of transgenic rabbits. All C1-inhibitors are being investigated for acute angioedema

  3. Relationships among Sensory Responsiveness, Anxiety, and Ritual Behaviors in Children with and without Atypical Sensory Responsiveness.

    Science.gov (United States)

    Bart, Orit; Bar-Shalita, Tami; Mansour, Hanin; Dar, Reuven

    2017-08-01

    To explore relationships between sensory responsiveness, anxiety, and ritual behaviors in boys with typical and atypical sensory responsiveness. Forty-eight boys, ages 5-9 participated in the study (28 boys with atypical sensory responsiveness and 20 controls). Atypical sensory responsiveness was defined as a score of ≤154 on the Short Sensory Profile. Parents completed the Sensory Profile, the Screen for Child Anxiety Related Emotional Disorders, and the Childhood Routines Inventory. Children with atypical sensory responsiveness had significantly higher levels of anxiety and a higher frequency of ritual behaviors than controls. Atypical sensory responsiveness was significantly related to both anxiety and ritual behaviors, with anxiety mediating the relationship between sensory modulation and ritual behaviors. The findings elucidate the potential consequences of atypical sensory responsiveness and could support the notion that ritual behaviors develop as a coping mechanism in response to anxiety stemming from primary difficulty in modulating sensory input.

  4. Sensory Hierarchical Organization and Reading.

    Science.gov (United States)

    Skapof, Jerome

    The purpose of this study was to judge the viability of an operational approach aimed at assessing response styles in reading using the hypothesis of sensory hierarchical organization. A sample of 103 middle-class children from a New York City public school, between the ages of five and seven, took part in a three phase experiment. Phase one…

  5. Sensory imagination and narrative perspective

    DEFF Research Database (Denmark)

    Grünbaum, Thor

    2013-01-01

    I argue that we can clarify and explain an important form of focalization or narrative perspective by the structure of perspective in sensory imagination. Understanding focalization in this way enables us to see why one particular form of focalization has to do with the representation of perceptu...

  6. Sensory Dissonance Using Memory Model

    DEFF Research Database (Denmark)

    Jensen, Karl Kristoffer

    2015-01-01

    Music may occur concurrently or in temporal sequences. Current machine-based methods for the estimation of qualities of the music are unable to take into account the influence of temporal context. A method for calculating dissonance from audio, called sensory dissonance is improved by the use...

  7. Pyridoxine-Induced Sensory Neuropathy

    OpenAIRE

    1995-01-01

    An 18-year-old man with seizures from birth was followed in the Department of Clinical Neurological Sciences, University of Western Ontario, London, and was found to have developed a sensory neuropathy by 2 years of age following treatment with pyridoxine in doses up to 2000 mg/day.

  8. Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia

    NARCIS (Netherlands)

    DeVries, DD; Went, LN; Bruyn, GW; Scholte, HR; Hofstra, RMW; Bolhuis, PA; vanOost, BA

    1996-01-01

    A rare form of Leber hereditary optic neuropathy (LHON) that is associated with hereditary spastic dystonia has been studied in a large Dutch family. Neuropathy and ophthalmological lesions were present together in some family members, whereas only one type of abnormality was found in others. mtDNA

  9. Proximate composition, bread characteristics and sensory ...

    African Journals Online (AJOL)

    Proximate composition, bread characteristics and sensory evaluation of ... African Journal of Food, Agriculture, Nutrition and Development ... This study was carried out to investigate proximate composition, bread characteristics and sensory ...

  10. Validity of Sensory Systems as Distinct Constructs

    OpenAIRE

    2014-01-01

    Confirmatory factor analysis testing whether sensory questionnaire items represented distinct sensory system constructs found, using data from two age groups, that such constructs can be measured validly using questionnaire data.

  11. A review on intelligent sensory modelling

    Science.gov (United States)

    Tham, H. J.; Tang, S. Y.; Teo, K. T. K.; Loh, S. P.

    2016-06-01

    Sensory evaluation plays an important role in the quality control of food productions. Sensory data obtained through sensory evaluation are generally subjective, vague and uncertain. Classically, factorial multivariate methods such as Principle Component Analysis (PCA), Partial Least Square (PLS) method, Multiple Regression (MLR) method and Response Surface Method (RSM) are the common tools used to analyse sensory data. These methods can model some of the sensory data but may not be robust enough to analyse nonlinear data. In these situations, intelligent modelling techniques such as Fuzzy Logic and Artificial neural network (ANNs) emerged to solve the vagueness and uncertainty of sensory data. This paper outlines literature of intelligent sensory modelling on sensory data analysis.

  12. Subclinical sensory involvement in monomelic amyotrophy.

    Science.gov (United States)

    Liao, Jenny P; Waclawik, Andrew J; Lotz, Barend P

    2005-12-01

    An 18-year-old woman presented with weakness and atrophy in her hand without associated sensory symptoms, preceding events, or structural abnormalities on neuroimaging. No sensory deficits were detected on neurologic examination. Electrophysiological studies showed not only the expected motor findings for monomelic amyotrophy (MA) in the affected limb, but also markedly reduced sensory nerve action potentials when compared with the unaffected side. These findings suggest that subclinical sensory involvement can exist in patients with otherwise classic presentations of MA.

  13. Hereditary Angioedema - Consequences of a New Treatment Paradigm in Denmark

    DEFF Research Database (Denmark)

    Bygum, Anette

    2014-01-01

    impact on their lives and restricted their physical activities. By December 2012, a total of 39 patients (49%) were practicing home treatment of acute attacks. Home therapy reduced the mean number of acute hospital visits by 84% and significantly improved burden of illness items. In conclusion, home......Experiences from a Danish patient cohort with hereditary angioedema are reported with focus on home therapy and burden of illness. Eighty patients have been prospectively followed over 11 years, having experienced a total of 7,809 attacks over 469 patient years. More than half of the patients...... stopped long-term prophylaxis with danazol or tranexamic acid and changed treatment regimen to on-demand treatment with C1 inhibitor concentrate or icatibant. At least 10% of the attacks remained un-treated. More than half of the patients felt that hereditary angioedema had a significant psychological...

  14. Spinal Exostosis in a Boy with Multiple Hereditary Exostoses

    Directory of Open Access Journals (Sweden)

    Ali Al Kaissi

    2013-01-01

    Full Text Available We report on a 13-year-old boy who presented with multiple hereditary exostosis and had development of back pain, associated with neurological deficits, and was found to have exostoses in the spinal canal. Spine radiograph showed a cauliflower-like abnormality of multiple exostoses of the posterior arch (pedicle of the thoracic vertebrae (T3–5. Reformatted CT scanning revealed the simultaneous development of intra- and extraspinal osteochondromatosis of T3–5. The spinal cord was compressed by the intraspinal exostosis. Our patient was surgically treated for intraspinal exostoses and showed cessation of neurological deficits. We report what might be a rare association of spinal cord compression in a patient with multiple hereditary exostoses.

  15. [Band 3 deficiency as a cause of hereditary spherocytosis].

    Science.gov (United States)

    Wada, Hideho; Suemori, Shin-Ichiro; Nakanishi, Hidekazu; Sugihara, Takashi

    2015-07-01

    Band 3 protein accounts for the largest percentage of whole erythrocyte membrane proteins. Abnormalities in this protein are closely associated with pathologies including hereditary spherocytosis (HS), Southeast Asian ovalocytosis and distant renal tubular acidosis. Currently, EMA binding capacity measurement in erythrocytes is the most useful screening test for diagnosing HS. We have also demonstrated reduced EMA binding capacity in patients with HS who have deficiencies of membrane proteins such as ankyrin not directly binding to EMA and who have as yet undetectable abnormalities of membrane proteins. However, even patients with hereditary elliptocytosis, who have a partial spectrin deficiency, were found to show reduced EMA binding capacity. Six of 7 had spherocytic elliptocytosis. Therefore, it is necessary to meticulously diagnose HS by ruling out all other possibilities.

  16. Benefits and risks of danazol in hereditary angioedema

    DEFF Research Database (Denmark)

    Bork, Konrad; Bygum, Anette; Hardt, Jochen

    2008-01-01

    . In the other patients, hereditary angioedema ran a mild course. The frequency of acute attacks during danazol treatment was reduced to 16.2%, and the attacks were considerably milder than before treatment. Laryngeal edema was reduced to 4.8%. Adverse effects (weight gain, virilization, menstrual irregularities......BACKGROUND: Hereditary angioedema (HAE) due to C1 inhibitor deficiency is clinically characterized by relapsing skin swellings, abdominal pain attacks, and life-threatening upper airway obstruction. Treatment with androgens prevents attacks for those with this condition. OBJECTIVE: To examine...... the benefits and risks of long-term treatment with danazol. METHODS: Data were generated retrospectively from 118 German and Danish patients who had HAE due to C1 inhibitor deficiency and were treated with danazol from 2 months to 30 years. The frequency and severity of acute attacks were registered before...

  17. The potential of disease management for neuromuscular hereditary disorders.

    Science.gov (United States)

    Chouinard, Maud-Christine; Gagnon, Cynthia; Laberge, Luc; Tremblay, Carmen; Côté, Charlotte; Leclerc, Nadine; Mathieu, Jean

    2009-01-01

    Neuromuscular hereditary disorders require long-term multidisciplinary rehabilitation management. Although the need for coordinated healthcare management has long been recognized, most neuromuscular disorders are still lacking clinical guidelines about their long-term management and structured evaluation plan with associated services. One of the most prevalent adult-onset neuromuscular disorders, myotonic dystrophy type 1, generally presents several comorbidities and a variable clinical picture, making management a constant challenge. This article presents a healthcare follow-up plan and proposes a nursing case management within a disease management program as an innovative and promising approach. This disease management program and model consists of eight components including population identification processes, evidence-based practice guidelines, collaborative practice, patient self-management education, and process outcomes evaluation (Disease Management Association of America, 2004). It is believed to have the potential to significantly improve healthcare management for neuromuscular hereditary disorders and will prove useful to nurses delivering and organizing services for this population.

  18. The Autosomal Recessive Inheritance of Hereditary Gingival Fibromatosis

    Directory of Open Access Journals (Sweden)

    Poulami Majumder

    2013-01-01

    Full Text Available Hereditary gingival fibromatosis (HGF is a rare condition which is marked by enlargement of gingival tissue that covers teeth to various extents leading to aesthetic disfigurement. This study presents a case of a 28-year-old female patient and 18-year-old male who belong to the same family suffering from HGF with chief complaint of overgrowing swelling gingiva. The presence of enlarged gingiva with the same eruption was found in their other family members with no concomitant drug or medical history, and the occurrence of HGF has been found in one generation of this family which may indicate the autosomal recessive inheritance pattern of HGF. Hereditary gingival fibromatosis is an idiopathic condition as its etiology is unknown and it was found to recur in some cases even after surgical treatment. Both patients underwent thorough oral prophylaxis and later surgical therapy to correct the deformity.

  19. Leber's hereditary optic neuropathy associated with multiple sclerosis: Harding's syndrome.

    Science.gov (United States)

    Parry-Jones, A R; Mitchell, J D; Gunarwardena, W J; Shaunak, S

    2008-04-01

    We describe a 32-year-old woman with sequential, severe, painless visual loss in one eye and then the other, and three temporally distinct episodes of neurological disturbance suggestive of demyelination in the spinal cord. She was positive for the T14484C mutation in the mitochondrial genome, one of three common mutations causing Leber's hereditary optic neuropathy. In addition, MRI identified areas of demyelination within the periventricular white matter of the brain and within the spinal cord. The coexistence of multiple sclerosis and Leber's hereditary optic neuropathy (Harding's syndrome) is known to occur more often than would be expected by chance; therefore, screening for the Leber's mutations in multiple sclerosis patients with severe visual loss should be considered because this has important prognostic and genetic implications.

  20. Glaucoma progression associated with Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Nucci, Carlo; Martucci, Alessio; Mancino, Raffaele; Cerulli, Luciano

    2013-02-01

    The purpose of this article is to describe a case of open-angle glaucoma progression associated with Leber's hereditary optic neuropathy. Single case analysis method is used. A 53-year-old woman with a previous diagnosis of glaucoma presented with progressive visual field loss. Complete ophthalmological examination and blood tests were negative for other concomitant diseases. Genetic counseling revealed mitochondrial DNA mutation compatible with the diagnosis of Leber's hereditary optic neuropathy. In conclusion, the case describes the concomitant occurrence of open-angle glaucoma and Leber's optic neuropathy. We hypothesize that the two diseases may have a cumulative effect on oxidative stress and retinal ganglion cell death with the consequent rapid progression of visual impairment. Screening for mitochondrial DNA mutations may be requested in patients with glaucoma who, despite pharmacologically controlled intraocular pressure, show rapid progression of the disease.

  1. Could Ossification of the Achilles Tendon Have a Hereditary Component?

    Directory of Open Access Journals (Sweden)

    Chawki Cortbaoui

    2013-01-01

    Full Text Available Ossification of the Achilles tendon (OTA is an unusual clinical condition. It is characterized by the presence of an ossified mass within the fibrocartilaginous substance of the Achilles tendon. The etiology of the ossification of the Achilles tendon is unknown. Review of the literature suggests that its etiology is multifactorial. The major contributing factors are trauma and surgery with other minor causes such as systemic diseases, metabolic conditions, and infections. To our knowledge, no previous reports suggest any genetic/hereditary predisposition in OAT. We report 3 siblings who have OAT with no history of any of the aforementioned predisposing factors. Could OAT have a hereditary component as one of its etiologies?

  2. Proteolipid protein 1 gene sequencing of hereditary spastic paraplegia

    Institute of Scientific and Technical Information of China (English)

    Yu Gao; Lumei Chi; Yinshi Jin; Guangxian Nan

    2012-01-01

    PCR amplification and sequencing of whole blood DNA from an individual with hereditary spastic paraplegia, as well as family members, revealed a fragment of proteolipid protein 1 (PLP1) gene exon 1, which excluded the possibility of isomer 1 expression for this family. The fragment sequence of exon 3 and exon 5 was consistent with the proteolipid protein 1 sequence at NCBI. In the proband samples, a PLP1 point mutation in exon 4 was detected at the basic group of position 844, T→C, phenylalanine→leucine. In proband samples from a male cousin, the basic group at position 844 was C, but gene sequencing signals revealed mixed signals of T and C, indicating possible mutation at this locus. Results demonstrated that changes in PLP1 exon 4 amino acids were associated with onset of hereditary spastic paraplegia.

  3. Hereditary Hemochromatosis Restores the Virulence of Plague Vaccine Strains

    Science.gov (United States)

    Quenee, Lauriane E.; Hermanas, Timothy M.; Ciletti, Nancy; Louvel, Helene; Miller, Nathan C.; Elli, Derek; Blaylock, Bill; Mitchell, Anthony; Schroeder, Jay; Krausz, Thomas; Kanabrocki, Joseph; Schneewind, Olaf

    2012-01-01

    Nonpigmented Yersinia pestis (pgm) strains are defective in scavenging host iron and have been used in live-attenuated vaccines to combat plague epidemics. Recently, a Y. pestis pgm strain was isolated from a researcher with hereditary hemochromatosis who died from laboratory-acquired plague. We used hemojuvelin-knockout (Hjv−/−) mice to examine whether iron-storage disease restores the virulence defects of nonpigmented Y. pestis. Unlike wild-type mice, Hjv−/− mice developed lethal plague when challenged with Y. pestis pgm strains. Immunization of Hjv−/− mice with a subunit vaccine that blocks Y. pestis type III secretion generated protection against plague. Thus, individuals with hereditary hemochromatosis may be protected with subunit vaccines but should not be exposed to live-attenuated plague vaccines. PMID:22896664

  4. Hereditary hearing loss: from human mutation to mechanism.

    Science.gov (United States)

    Lenz, Danielle R; Avraham, Karen B

    2011-11-01

    The genetic heterogeneity of hereditary hearing loss is thus far represented by hundreds of genes encoding a large variety of proteins. Mutations in these genes have been discovered for patients with different modes of inheritance and types of hearing loss, ranging from syndromic to non-syndromic and mild to profound. In many cases, the mechanisms whereby the mutations lead to hearing loss have been partly elucidated using cell culture systems and mouse and other animal models. The discovery of the genes has completely changed the practice of genetic counseling in this area, providing potential diagnosis in many cases that can be coupled with clinical phenotypes and offer predictive information for families. In this review we provide three examples of gene discovery in families with hereditary hearing loss, all associated with elucidation of some of the mechanisms leading to hair cell degeneration and pathology of deafness.

  5. [Clinical and molecular genetic analysis of hereditary optic neuropathies].

    Science.gov (United States)

    Avetisov, S É; Sheremet, N L; Vorob'eva, O K; Eliseeva, É G; Chukhrova, A L; Loginova, A N; Khanakova, N A; Poliakov, A V

    2013-01-01

    DNA samples of 50 patients with optic neuropathy (ON) associated with congenital cataract were studied to find 3 major mt-DNA mutations (m.11778G>A, m.3460G>A, m.14484T>C), mutations in "hot" regions of OPA 1 gene (exons 8, 14, 15, 16, 18, 27, 28) and in the entire coding sequence of OPA3 gene for molecular genetic confirmation of diagnosis of hereditary Leber and autosomal dominant ON. Primary mutations of mtDNA responsible for hereditary Leber ON were found in 16 patients (32%). Pathogenic mutations of OPAl gene (c.869G>A and c. 2850delT) were identified in 2 patients (4%), these mutations were not found in the literature. OPA3 gene mutations were not revealed.

  6. [Hereditary ataxias, spastic parapareses and neuropathies in Eastern Canada].

    Science.gov (United States)

    Dupré, N; Chrestian, N; Thiffault, I; Brais, B; Rouleau, G A; Bouchard, J-P

    2008-01-01

    It has been demonstrated, for many inherited diseases, that historical events have shaped the various regional gene pools of Eastern Canada. In so doing, it has given rise to the increased prevalence of some rare diseases due, to founder effects. The following neurogenetic disorders were first identified in patients from Eastern Canada: AOA-2, Arsacs, HSN-2, Arca-1, HMSN/ACC and Arsal. The population of Eastern Canada, we are convinced, will still allow the identification of new rare forms of hereditary ataxias, spastic parapareses and neuropathies as well as contribute to the uncovering of their mutated genes. We have summarized our current knowledge of the various hereditary ataxias, spastic parapareses and neuropathies in Eastern Canada. The study of the more common and homogenous features of these diseases has been largely completed.

  7. A Case of Hereditary Leiomyomatosis and Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Sarah Mehrtens

    2016-01-01

    Full Text Available A 49-year-old lady presented with multiple recurring painful lesions over her thighs, arms, and back. Past medical history included a left sided nephrectomy for renal cell carcinoma and a hysterectomy for multiple uterine fibroids (leiomyomas. Histopathological examination revealed changes consistent with pilar leiomyomas. Gene mutation analysis confirmed a diagnosis of hereditary leiomyomatosis and renal cell carcinoma. Hereditary leiomyomatosis and renal cell carcinoma is an uncommon autosomal dominant condition characterised by the concurrent presentation of cutaneous and uterine leiomyomas. Renal cell carcinoma associated with this condition is more aggressive and a significant cause of mortality. Due to this association with potentially fatal renal cell carcinoma we felt that it was important to highlight this case with an update on pathophysiology and management.

  8. The Molecular Basis of Hereditary Enamel Defects in Humans

    Science.gov (United States)

    Carrion, I.A.; Morris, C.

    2015-01-01

    The formation of human enamel is highly regulated at the molecular level and involves thousands of genes. Requisites for development of this highly mineralized tissue include cell differentiation; production of a unique extracellular matrix; processing of the extracellular matrix; altering of cell function during different stages of enamel formation; cell movement and attachment; regulation of ion and protein movement; and regulation of hydration, pH, and other conditions of the microenvironment, to name just a few. Not surprising, there is a plethora of hereditary conditions with an enamel phenotype. The objective of this review was to identify the hereditary conditions listed on Online Mendelian Inheritance in Man (OMIM) that have an associated enamel phenotype and whether a causative gene has been identified. The OMIM database was searched with the terms amelogenesis, enamel, dental, and tooth, and all results were screened by 2 individuals to determine if an enamel phenotype was identified. Gene and gene product function was reviewed on OMIM and from publications identified in PubMed. The search strategy revealed 91 conditions listed in OMIM as having an enamel phenotype, and of those, 71 have a known molecular etiology or linked genetic loci. The purported protein function of those conditions with a known genetic basis included enzymes, regulatory proteins, extracellular matrix proteins, transcription factors, and transmembrane proteins. The most common enamel phenotype was a deficient amount of enamel, or enamel hypoplasia, with hypomineralization defects being reported less frequently. Knowing these molecular defects allows an initial cataloging of molecular pathways that lead to hereditary enamel defects in humans. This knowledge provides insight into the diverse molecular pathways involved in enamel formation and can be useful when searching for the genetic etiology of hereditary conditions that involve enamel. PMID:25389004

  9. Hereditary Nonsyndromic Gingival Fibromatosis: Report of Family Case Series

    Directory of Open Access Journals (Sweden)

    Syed Wali Peeran

    2013-01-01

    Full Text Available Hereditary gingival fibromatosis (HGF is a rare, benign disorder with slowly progressive enlargement of maxillary and mandibular gingiva. Herewith, we report the first case series of HGF presenting among mother and all of her 3 children. Their complaints included unaesthetic appearance due to gingival growth, malocclusion, and difficulty in mastication. Conventional gingivectomy with oral hygiene measures and regular followup is the treatment of choice for such presentation.

  10. A Rare Cause of Abdominal Pain in Children: Hereditary Angioedema

    Directory of Open Access Journals (Sweden)

    Deniz Özçeker

    2015-03-01

    Full Text Available Hereditary angioedema (HA is a rare, autosomal-dominant genetic disorder presenting with recurrent attacks of angioedema. The most commonly involved organs include the extremites, face, neck, upper respiratory tract, genital region and the gastrointestinal tract. Edema of the intestinal mucosa can cause temporary obstruction and severe abdominal pain that can be confused with acute abdomen. Pediatricians and emergency physicians should keep in mind this rare disease in the differential diagnosis of severe abdominal pain.

  11. Hereditary angioedema: quality of life in Brazilian patients

    Directory of Open Access Journals (Sweden)

    Maria Abadia Consuelo M. S. Gomide

    2013-01-01

    Full Text Available OBJECTIVE: Hereditary angioedema is a serious medical condition caused by a rare autosomal dominant genetic disorder and it is associated with deficient production or dysfunction of the C1 esterase inhibitor. In most cases, affected patients experience unexpected and recurrent crises of subcutaneous, gastrointestinal and laryngeal edema. The unpredictability, intensity and other factors associated with the disease impact the quality of life of hereditary angioedema patients. We evaluated the quality of life in Brazilian hereditary angioedema patients. METHODS: Patients older than 15 years with any severity of hereditary angioedema and laboratory confirmation of C1 inhibitor deficiency were included. Two questionnaires were used: a clinical questionnaire and the SF-36 (a generic questionnaire. This protocol was approved by the Ethics Committee of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. RESULTS: The SF-36 showed that 90.4% (mean of all the patients had a score below 70 and 9.6% had scores equal to or higher than 70. The scores of the eight dimensions ranged from 51.03 to 75.95; vitality and social aspects were more affected than other arenas. The internal consistency of the evaluation was demonstrated by a Cronbach's alpha value above 0.7 in seven of the eight domains. CONCLUSIONS: In this study, Brazilian patients demonstrated an impaired quality of life, as measured by the SF-36. The most affected domains were those related to vitality and social characteristics. The generic SF-36 questionnaire was relevant to the evaluation of quality of life; however, there is a need for more specific instruments for better evaluation.

  12. HEREDITARY INTRAVENTRICULAR CONDUCTION DISORDERS IN THE FAMILY FROM KRASNOYARSK

    Directory of Open Access Journals (Sweden)

    A. A. Chernova

    2011-01-01

    Full Text Available Pedigree of the family from Krasnoyarsk city with hereditary disorders of intracardiac conduction was studied. The diagnosis of each family member was verified by electrocardiography (ECG, echocardiography , bicycle ergometry , ECG Holter monitoring. The family 10-year follow-up showed familial aggregation of intracardiac conduction disorders in grandson, niece, son of the proband niece, ie, in the III-degree relatives. Family history of III-degree relatives with intracardiac conduction disorders and discordant pathology is identified.

  13. The molecular basis of hereditary enamel defects in humans.

    Science.gov (United States)

    Wright, J T; Carrion, I A; Morris, C

    2015-01-01

    The formation of human enamel is highly regulated at the molecular level and involves thousands of genes. Requisites for development of this highly mineralized tissue include cell differentiation; production of a unique extracellular matrix; processing of the extracellular matrix; altering of cell function during different stages of enamel formation; cell movement and attachment; regulation of ion and protein movement; and regulation of hydration, pH, and other conditions of the microenvironment, to name just a few. Not surprising, there is a plethora of hereditary conditions with an enamel phenotype. The objective of this review was to identify the hereditary conditions listed on Online Mendelian Inheritance in Man (OMIM) that have an associated enamel phenotype and whether a causative gene has been identified. The OMIM database was searched with the terms amelogenesis, enamel, dental, and tooth, and all results were screened by 2 individuals to determine if an enamel phenotype was identified. Gene and gene product function was reviewed on OMIM and from publications identified in PubMed. The search strategy revealed 91 conditions listed in OMIM as having an enamel phenotype, and of those, 71 have a known molecular etiology or linked genetic loci. The purported protein function of those conditions with a known genetic basis included enzymes, regulatory proteins, extracellular matrix proteins, transcription factors, and transmembrane proteins. The most common enamel phenotype was a deficient amount of enamel, or enamel hypoplasia, with hypomineralization defects being reported less frequently. Knowing these molecular defects allows an initial cataloging of molecular pathways that lead to hereditary enamel defects in humans. This knowledge provides insight into the diverse molecular pathways involved in enamel formation and can be useful when searching for the genetic etiology of hereditary conditions that involve enamel.

  14. Hereditary vitamin D rickets: a case series in a family.

    Science.gov (United States)

    Surender, Kumar; Kochar, I P S; Ahmad, Ayesha; Kapoor, Meenal

    2014-11-01

    Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disorder characterized by end-organ resistance to 1α,25-dihydroxyvitamin D3 (1,25D3). Clinically, the syndrome is recognized by severe early onset rickets with bowing of the lower extremities, short stature, and often alopecia. Here, we report a case series on three siblings who had HVDRR with varied clinical findings.

  15. Renal fructose-metabolizing enzymes: significance in hereditary fructose intolerance.

    Science.gov (United States)

    Kranhold, J F; Loh, D; Morris, R C

    1969-07-25

    In patients with hereditary fructose intolerance, which is characterized by deficient aldolase activity toward fructose-1-phosphate, fructose induces a renal tubular dysfunction that implicates only the proximal convoluted tubule. Because normal metabolism of fructose by way of fructose-1-phosphate requires fructokinase, aldolase "B," and triokinase, the exclusively cortical location of these enzymes indicates that the medulla is not involved in the metabolic abnormality presumably causal of the renal dysfunction.

  16. A possible case of transient hereditary fructose intolerance.

    Science.gov (United States)

    Catto-Smith, A G; Adams, A

    1993-01-01

    A patient is described who presented with the signs and symptoms of hereditary fructose intolerance a few hours after her first fructose challenge. The diagnosis was confirmed by the demonstration of reduced activity of hepatic aldolase B towards fructose-1-phosphate. A second liver biopsy 10 months later had normal aldolase B activity towards fructose-1-phosphate and a fructose tolerance test was also normal. A possible explanation for these findings is proposed.

  17. One novel transcript of human hereditary multipleexostoses 2 (EXT2)

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The encoding sequence of human hereditary multiple exostoses gene EXT2.1 is 30 bp longer than EXT2, and they differ in a sequence of 90 base pairs. In order to clarify EXT2.1 structure, this 90 bp sequence was analyzed with the Human Sequence Draft, a database provided by Celera Genomics. The result shows that EXT2.1 is a novel transcript of EXT2 gene, suggesting a rare event of alternative splicing.

  18. Hereditary spastic paraplegia with a thin corpus callosum

    Energy Technology Data Exchange (ETDEWEB)

    Somasundaram, Sivaraman; Kesavadas, Chandrasekharan [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Imaging Sciences and Interventional Radiology, Trivandrum (India); Raghavendra, Seetharam; Singh, Atampreet; Nair, Muraleedharan [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Neurology, Trivandrum (India)

    2007-05-15

    We report a 15-year-old boy with autosomal recessive complicated hereditary spastic paraplegia with a thin corpus callosum (HSP-TCC). The involvement of the corpus callosum was characteristic with the genu and body predominantly affected with relative sparing of the splenium. HSP-TCC is being increasingly recognized over a wider geographical area than earlier believed. We now report a case of HSP-TCC from the Indian subcontinent. (orig.)

  19. Sensory nerve conduction studies in neuralgic amyotrophy.

    NARCIS (Netherlands)

    Alfen, N. van; Huisman, W.J.; Overeem, S.; Engelen, B.G.M. van; Zwarts, M.J.

    2009-01-01

    Neuralgic amyotrophy is a painful, episodic peripheral nerve disorder localized to the brachial plexus. Sensory symptoms occur in 80% of the patients. We assessed the frequency of abnormalities in sensory nerve conduction studies of the lateral and medial antebrachial cutaneous, radial sensory, medi

  20. Motor-sensory confluence in tactile perception.

    Science.gov (United States)

    Saig, Avraham; Gordon, Goren; Assa, Eldad; Arieli, Amos; Ahissar, Ehud

    2012-10-03

    Perception involves motor control of sensory organs. However, the dynamics underlying emergence of perception from motor-sensory interactions are not yet known. Two extreme possibilities are as follows: (1) motor and sensory signals interact within an open-loop scheme in which motor signals determine sensory sampling but are not affected by sensory processing and (2) motor and sensory signals are affected by each other within a closed-loop scheme. We studied the scheme of motor-sensory interactions in humans using a novel object localization task that enabled monitoring the relevant overt motor and sensory variables. We found that motor variables were dynamically controlled within each perceptual trial, such that they gradually converged to steady values. Training on this task resulted in improvement in perceptual acuity, which was achieved solely by changes in motor variables, without any change in the acuity of sensory readout. The within-trial dynamics is captured by a hierarchical closed-loop model in which lower loops actively maintain constant sensory coding, and higher loops maintain constant sensory update flow. These findings demonstrate interchangeability of motor and sensory variables in perception, motor convergence during perception, and a consistent hierarchical closed-loop perceptual model.

  1. An overview of novel therapies for acute hereditary angioedema.

    Science.gov (United States)

    Firszt, Rafael; Frank, Michael M

    2010-12-01

    Hereditary angioedema is an episodic swelling disorder with autosomal dominant inheritance. Attacks are characterized by nonpitting edema of external or mucosal body surfaces. Patients often present with swelling of the extremities, abdominal pain, and swelling of the mouth and throat, which can at times lead to asphyxiation. The disease is caused by a mutation in the gene encoding the complement C1-inhibitor protein, which leads to unregulated production of bradykinin. Long-term therapy has depended on the use of attenuated androgens or plasmin inhibitors but in the US there was, until recently, no specific therapy for acute attacks. As well, many patients with hereditary angioedema in the US were either not adequately controlled on previously available therapies or required doses of medications that exposed them to the risk of serious adverse effects. Five companies have completed or are currently conducting phase III clinical trials in the development of specific therapies to terminate acute attacks or to be used as prophylaxis. These products are based on either replacement therapy with purified plasma-derived or recombinant C1-inhibitor, or inhibition of the kinin-generating pathways with a recombinant plasma kallikrein inhibitor or bradykinin type 2 receptor antagonist. Published studies thus far suggest that all of these products are likely to be effective. These new therapies will likely lead to a totally new approach in treating hereditary angioedema.

  2. Small Heat Shock Proteins and Distal Hereditary Neuropathies.

    Science.gov (United States)

    Nefedova, V V; Muranova, L K; Sudnitsyna, M V; Ryzhavskaya, A S; Gusev, N B

    2015-12-01

    Classification of small heat shock proteins (sHsp) is presented and processes regulated by sHsp are described. Symptoms of hereditary distal neuropathy are described and the genes whose mutations are associated with development of this congenital disease are listed. The literature data and our own results concerning physicochemical properties of HspB1 mutants associated with Charcot-Marie-Tooth disease are analyzed. Mutations of HspB1, associated with hereditary motor neuron disease, can be accompanied by change of the size of HspB1 oligomers, by decreased stability under unfavorable conditions, by changes in the interaction with protein partners, and as a rule by decrease of chaperone-like activity. The largest part of these mutations is accompanied by change of oligomer stability (that can be either increased or decreased) or by change of intermonomer interaction inside an oligomer. Data on point mutation of HspB3 associated with axonal neuropathy are presented. Data concerning point mutations of Lys141 of HspB8 and those associated with hereditary neuropathy and different forms of Charcot-Marie-Tooth disease are analyzed. It is supposed that point mutations of sHsp associated with distal neuropathies lead either to loss of function (for instance, decrease of chaperone-like activity) or to gain of harmful functions (for instance, increase of interaction with certain protein partners).

  3. Heterogeneity of Hereditary Hearing Loss in Iran: a Comprehensive Review.

    Science.gov (United States)

    Beheshtian, Maryam; Babanejad, Mojgan; Azaiez, Hela; Bazazzadegan, Niloofar; Kolbe, Diana; Sloan-Heggen, Christina; Arzhangi, Sanaz; Booth, Kevin; Mohseni, Marzieh; Frees, Kathy; Azizi, Mohammad Hossein; Daneshi, Ahmad; Farhadi, Mohammad; Kahrizi, Kimia; Smith, Richard Jh; Najmabadi, Hossein

    2016-10-01

    A significant contribution to the causes of hereditary hearing impairment comes from genetic factors. More than 120 genes and 160 loci have been identified to be involved in hearing impairment. Given that consanguine populations are more vulnerable to most inherited diseases, such as hereditary hearing loss (HHL), the genetic picture of HHL among the Iranian population, which consists of at least eight ethnic subgroups with a high rate of intermarriage, is expected to be highly heterogeneous. Using an electronic literature review through various databases such as PubMed, MEDLINE, and Scopus, we review the current picture of HHL in Iran. In this review, we present more than 39 deafness genes reported to cause non-syndromic HHL in Iran, of which the most prevalent causative genes include GJB2, SLC26A4, MYO15A, and MYO7A. In addition, we highlight some of the more common genetic causes of syndromic HHL in Iran. These results are of importance for further investigation and elucidation of the molecular basis of HHL in Iran and also for developing a national diagnostic tool tailored to the Iranian context enabling early and efficient diagnosis of hereditary hearing impairment.

  4. Management of hereditary angioedema in pregnant women: a review

    Directory of Open Access Journals (Sweden)

    Caballero T

    2014-09-01

    Full Text Available Teresa Caballero,1,2 Julio Canabal,1 Daniela Rivero-Paparoni,1 Rosario Cabañas1 1Hospital La Paz Institute for Health Research, (IdiPaz 2Biomedical Research Network on Rare Diseases-U754 (CIBERER, Madrid, Spain Abstract: Three types of hereditary angioedema (HAE have been described: two are due to C1 inhibitor (C1-INH deficiency (C1-INH-HAE types I and II and one is characterized by normal C1-INH (nC1-INH-HAE. The management of pregnancy in patients with HAE is often a clinical challenge owing to potential worsening of the disease in relation to the physiological increase in estrogens and the limited treatment options. This review addresses the potential influence of pregnancy on the clinical severity of hereditary angioedema and the management of this disease during pregnancy with currently available treatments. Keywords: hereditary angioedema, pregnancy, female, treatment, C1 inhibitor concentrate, tranexamic acid

  5. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    DEFF Research Database (Denmark)

    Bowen, Tom; Cicardi, Marco; Farkas, Henriette

    2010-01-01

    ABSTRACT: BACKGROUND: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007...... International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. OBJECTIVE: To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010). METHODS: The Canadian Hereditary Angioedema Network (CHAEN...... approach. The Consensus document was reviewed at the meeting and then circulated for review. RESULTS: This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference. CONCLUSIONS: Consensus approach is only...

  6. Sensory feedback in interlimb coordination

    DEFF Research Database (Denmark)

    Gervasio, Sabata; Voigt, Michael; Kersting, Uwe G.

    2017-01-01

    direct communication between the two sides without the need for the involvement of higher centers. These may also exist in humans since sensory feedback elicited by tibial nerve stimulation on one side (ipsilateral) can affect the muscles activation in the opposite side (contralateral), provoking short......-latency crossed responses (SLCRs). The current study investigated whether contralateral afferent feedback contributes to the mechanism controlling the SLCR in human gastrocnemius muscle. Surface electromyogram, kinematic and kinetic data were recorded from subjects during normal walking and hybrid walking (with.......04). Moreover, estimated spindle secondary afferent and Golgi tendon organ activity were significantly different (P ≤ 0.01) when opposite responses have been observed, that is during normal (facilitation) and hybrid walking (inhibition) conditions. Contralateral sensory feedback, specifically spindle secondary...

  7. Hereditary Spherocytosis in a Middle-aged Man Complicated with Common Bile Duct Stones.

    Science.gov (United States)

    Sawahara, Hiroaki; Iwamuro, Masaya; Harada, Ryo; Yoshioka, Masao; Niguma, Takefumi; Mimura, Tetsushige; Yamamoto, Kazuhide

    2015-01-01

    Hereditary spherocytosis is the most common form of hemolytic anemia and is characterized by spherical, osmotically fragile erythrocytes that are selectively trapped by the spleen. Hereditary spherocytosis is typically diagnosed in childhood. We herein experienced a rare case of hereditary spherocytosis diagnosed in middle age. The patient presented with cholelithiasis and hyperbilirubinemia. He had no anemia and was asymptomatic with mild splenomegaly. In the differential diagnosis of these symptoms, the possibility of hereditary spherocytosis should be considered, even in patients who are middle-aged and lack anemia.

  8. Dispersion of compound muscle action potential in hereditary neuropathies and chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Stanton, Michael; Pannoni, Valerie; Lewis, Richard A; Logigian, Eric L; Naguib, Demian; Shy, Michael E; Cleland, James; Herrmann, David N

    2006-10-01

    Distal compound muscle action potential (DCMAP) dispersion, defined as a DCMAP duration > or = 9 ms, and proximal-distal (P-D) CMAP dispersion are considered useful in the electrodiagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Distal and P-D CMAP dispersion have not been fully studied in hereditary neuropathies, and it is not known whether these measures distinguish hereditary from acquired demyelination. We compared DCMAP duration and P-D CMAP dispersion in 91 genetically characterized hereditary neuropathies and 33 subjects with CIDP. DCMAP dispersion was more frequent in nerves affected by CIDP (41.5%) than in Charcot-Marie-Tooth disease (CMT)1A (24.4%), CMT1B (7.4%), hereditary neuropathy with liability to pressure palsies (HNPP) (10.5%), or CMTX (9.8%). P-D CMAP dispersion was more frequent in CIDP (27.7% of nerves) than in hereditary neuropathies (16.3%) when applying American Academy of Neurology (AAN) criteria; however, its frequency was similar in CIDP and the hereditary neuropathies using the more restrictive criteria of the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM). Although dispersion is more common in CIDP than in the hereditary neuropathies, DCMAP and P-D dispersion occur in at least one motor nerve in a significant proportion of hereditary neuropathies, and cannot be used in isolation to distinguish acquired from hereditary demyelination.

  9. Oral sensory dysfunction following radiotherapy.

    Science.gov (United States)

    Bearelly, Shethal; Wang, Steven J; Cheung, Steven W

    2017-10-01

    To assess differences in oral tactile sensation between subjects who have undergone radiation therapy (XRT) compared to healthy controls. Cross-sectional cohort comparison. Thirty-four subjects with a history of XRT were compared with 23 healthy controls. There was no difference in age (P = .23), but there were slightly more males in the XRT cohort (P = .03). The mean (standard deviation) time after XRT completion was 3.84 (4.84) years. Fifty-six percent of the XRT cohort received chemotherapy. Using our previously validated methodology to measure oral tactile sensory threshold quantitatively with Cheung-Bearelly monofilaments, sensory thresholds of four subsites (anterior tongue, buccal mucosa, posterior tongue, soft palate) were compared for the two cohorts. Site-by-site comparisons showed higher forces were required for stimulus detection at all four subsites among subjects in the XRT cohort compared to healthy controls. Mean force in grams for XRT versus control cohorts were: anterior tongue, 0.39 (1.0) versus 0.02 (0.01); buccal mucosa, 0.42 (0.95) versus 0.06 (0.05); posterior tongue, 0.76 (1.46) versus 0.10 (0.07); and soft palate, 0.86 (1.47) versus 0.08 (0.05) (P sensory dysfunction, manifested by increased tactile forces required for stimulus detection. The magnitude of sensory impairment is 18.7 dB. 3b. Laryngoscope, 127:2282-2286, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  10. Sensory Coordination of Insect Flight

    Science.gov (United States)

    2010-10-22

    migratory flight in the neotropical moth Urania fulgens. Biology Letters, 6, 406–409. Sane S.P.* and McHenry M.J. (2009) The biomechanics of sensory...organs. Integrative and Comparative Biology , 49(6):i8-i23. Zhao, L., Huang, Q., Deng, X. and Sane, S.P. (2010). Aerodynamic effects of flexibility...and behavioral insights into insect flight Invited Speaker, International Workshop on Nocturnal Pollination , March 24-27, 2009 Indian Institute of

  11. Methodology of oral sensory tests.

    Science.gov (United States)

    Jacobs, R; Wu, C-H; Van Loven, K; Desnyder, M; Kolenaar, B; Van Steenberghed, D

    2002-08-01

    Different methods of oral sensory tests including light touch sensation, two-point discrimination, vibrotactile function and thermal sensation were compared. Healthy subjects were tested to assess the results obtained from two psychophysical approaches, namely the staircase and the ascending & descending method of limits for light touch sensation and two-point discrimination. Both methods appeared to be reliable for examining oral sensory function. The effect of topical anaesthesia was also evaluated but no conclusion could be drawn as too few subjects were involved. Newly developed simple testing tools for two-point discrimination and thermal sensation in a clinical situation were developed prior to this study and tested for their reproducibility. Thermal sensation could be reliably detected in repeated trials. Although the hand-held instruments have some drawbacks, the outcome of these instruments in a clinical environment is suitable for assessing oral sensory function. Three different frequencies (32, 128 and 256 Hz) were used to estimate the vibrotactile function. Different threshold levels were found at different frequencies.

  12. Stomatin and sensory neuron mechanotransduction.

    Science.gov (United States)

    Martinez-Salgado, Carlos; Benckendorff, Anne G; Chiang, Li-Yang; Wang, Rui; Milenkovic, Nevena; Wetzel, Christiane; Hu, Jing; Stucky, Cheryl L; Parra, Marilyn G; Mohandas, Narla; Lewin, Gary R

    2007-12-01

    Somatic sensory neurons of the dorsal root ganglia are necessary for a large part of our mechanosensory experience. However, we only have a good knowledge of the molecules required for mechanotransduction in simple invertebrates such as the nematode Caenorhabiditis elegans. In C. elegans, a number of so-called mec genes have been isolated that are required for the transduction of body touch. One such gene, mec-2 codes for an integral membrane protein of the stomatin family, a large group of genes with a stomatin homology domain. Using stomatin null mutant mice, we have tested the hypothesis that the founding member of this family, stomatin might play a role in the transduction of mechanical stimuli by primary sensory neurons. We used the in vitro mouse skin nerve preparation to record from a large population of low- and high-threshold mechanoreceptors with myelinated A-fiber (n = 553) and unmyelinated C-fiber (n = 157) axons. One subtype of mechanoreceptor, the d-hair receptor, which is a rapidly adapting mechanoreceptor, had reduced sensitivity to mechanical stimulation in the absence of stomatin. Other cutaneous mechanoreceptors, including nociceptive C-fibers were not affected by the absence of a functional stomatin protein. Patch-clamp analysis of presumptive D-hair receptor mechanoreceptive neurons, which were identified by a characteristic rosette morphology in culture, showed no change in membrane excitability in the absence of the stomatin protein. We conclude that stomatin is required for normal mechanotransduction in a subpopulation of vertebrate sensory neurons.

  13. Sensory evaluation of buffalo butter

    Directory of Open Access Journals (Sweden)

    J.C.S. Carneiro

    2010-02-01

    Full Text Available Butter obtained from buffalo milk was compared with commercial products obtained from cow milk. One buffalo butter and two cow butters were subjected to sensory analysis using non-trained panelists. The acceptance related to sensorial characteristics (color, flavor, and firmness was evaluated through a 9 point structured hedonic scale varying from “I displeased extremely” to “I liked extremely”. Analysis of variance (ANOVA was performed to evaluate the sensory characteristics and the means were compared by Tukey’s Test at 5% of significance. The buffalo butter received lower scores than the others for all attributes. The greatest difference was observed for color, as the buffalo butter exhibited a white color contrasting with the yellow color of commercial butters, which is the pattern expected by the consumers. For flavor and firmness attributes, the buffalo butter received scores similar to the commercial products. These results show. These results shows that the buffalo’s butter has a good acceptance on local market, and this could be improved through the correction of product’s color, what can be obtained by adding a dye.

  14. The Chemical Background for Sensory Quality

    DEFF Research Database (Denmark)

    Zhang, Shujuan

    In the food industry, high sensory quality and stability of products are crucial factors for consumer satisfaction and market shares. Sensory quality is normally being evaluated by two major approaches: instrumental (volatile and nonvolatile compounds) approach and sensory approach by trained...... and sensory methods in understanding the pre-fermentation treatment on sensory quality of wine (Study 3). In Study 4, the RATA method was used to provide the intensity of significant sensory descriptors that discriminate the significant differences between chocolate samples. Part three step by step moves......; detecting changes of volatiles as a result of production errors in chocolate production, and monitoring aroma release provide useful information to food sensory quality control. For each application, both techniques were faced with challenges that need to be handled in different ways. Due to the complex...

  15. Bioinspired Sensory Systems for Shear Flow Detection

    Science.gov (United States)

    Colvert, Brendan; Chen, Kevin K.; Kanso, Eva

    2017-03-01

    Aquatic organisms such as copepods exhibit remarkable responses to changes in ambient flows, especially shear gradients, when foraging, mating and escaping. To accomplish these tasks, the sensory system of the organism must decode the local sensory measurements to detect the flow properties. Evidence suggests that organisms sense differences in the hydrodynamic signal rather than absolute values of the ambient flow. In this paper, we develop a mathematical framework for shear flow detection using a bioinspired sensory system that measures only differences in velocity. We show that the sensory system is capable of reconstructing the properties of the ambient shear flow under certain conditions on the flow sensors. We discuss these conditions and provide explicit expressions for processing the sensory measurements and extracting the flow properties. These findings suggest that by combining suitable velocity sensors and physics-based methods for decoding sensory measurements, we obtain a powerful approach for understanding and developing underwater sensory systems.

  16. Cranial nerves palsy as an initial feature of an early onset distal hereditary motor neuropathy--a new distal hereditary motor neuropathy phenotype.

    Science.gov (United States)

    Haberlová, J; Claeys, K G; De Jonghe, P; Seeman, P

    2009-06-01

    Distal hereditary motor neuropathy is a heterogeneous group of disorders characterised by a pure motor axonal neuropathy. It is occasionally associated with additional signs such as facial weakness, vocal cord paralysis, weakness of the diaphragm, and pyramidal signs. Although predominantly the inheritance is autosomal dominant, all types of inheritance have been described. Here we report a Czech family with cranial nerves palsy as an initial feature of a non progressive infantile onset dominant distal hereditary motor neuropathy. This family may represent a new subtype of distal hereditary motor neuropathy.

  17. Hereditary coproporphyria from clinician’s point of view: A case report

    Directory of Open Access Journals (Sweden)

    Savić Željka

    2013-01-01

    Full Text Available Introduction. Acute hepatic porphyrias can mimic a range of unrelated diseases and conditions that may occur independently of porphyria and trigger their initial manifestations and further attacks. Case Report. A 46-year-old female patient was subjected to cholecystectomy for biliary colic. Histopathological analysis revealed acute purulent exacerbation of chronic cholecystitis. On the 8th day post surgery, the patient was rehospitalized for nausea, abdominal pain, weakness and faintness, poor general condition, hypertension, tachycardia, apathy and profuse sweating. Laboratory findings revealed hyponatremia, hypokalemia, and metabolic alkalosis. Exploratory laparotomy did not detect a pathomorphological substrate. The patient was transferred to surgery department of the tertiary care institution. Due to metabolic imbalance, she was transferred to the Department of Endocrinology with signs of paleness, profuse sweating, tachycardia, and tachydyspnoea. The cardiologist performed echocardiography. The patient was diagnosed to have acute left ventricular failure and sub-acute myocardial infarction and transferred to the Department of Cardiology. Coronarography findings were normal. Cramps and pain in the legs with sensory loss, general weakness, apathy and mental confusion suggested acute hepatic porphyria. Thus, hereditary coproporphyria was diagnosed in the second month of illness. The treatment was continued at the Department of Gastroenterology. Clinical manifestations included polyneuropathy, flaccid paraparesis and acute brain syndrome, precordial oppressions and tachycardia. Haem arginate and hypertonic glucose were applied. The condition of the patient gradually improved. Conclusion. Porphyrias should always be taken into consideration in doubtful, frequently dramatic clinical pictures characterized by neurovisceral symptoms and precipitating factors of acute porphyria attacks must never be neglected.

  18. Molecular and hereditary mechanisms of sensorineural hearing loss with focus on selected endocrinopathies.

    Science.gov (United States)

    Masindova, I; Varga, L; Stanik, J; Valentinova, L; Profant, M; Klimes, I; Gasperikova, D

    2012-07-01

    Hearing loss is one of the most widespread sensory disorders. The incidence of deafness in general population is 1:1000 newborns. About one half of the cases of the congenital sensorineural hearing loss (SNHL) is inherited. Recessive mutations in the gap junction beta 2 (GJB2) gene are the most common genetic causes of the nonsyndromic SNHL. The GJB2 encodes a protein connexin 26 which forms a subunit of gap junction essential for the correct function of the inner ear. The syndromic SNHL is associated with a wide range of other symptoms, which encompass also dysfunctions of endocrine organs. The Pendred syndrome associated with the hearing impairment is characterized by a prelingual, bilateral sever to profound SNHL, goiter, and iodine organification defect. It is an autosomal recessive disorder, which develops due to mutations in pendrin, an anion channel encoded by SLC26A4 gene. Another important type of syndromic hearing loss is the Maternally Inherited Diabetes and Deafness syndrome, which is caused by several mitochondrial DNA mutations. These mutations are clinically manifested by a hearing impairment with development of the diabetes in the adult age. Hearing impairment occurs during puberty when sensation of high frequency tones is affected following with further progress to profound bilateral sensorineural hearing impairment in the whole frequency range. This review deals with the molecular mechanisms of common genetic causes of the hereditary SNHL along with the selected endocrinopathies emphasizing that the DNA analyses along with the functional studies significantly contribute to the early SNHL diagnosis followed by personalized therapy and genetic counseling.

  19. Extra-visual functional and structural connection abnormalities in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Rocca, Maria A; Valsasina, Paola; Pagani, Elisabetta; Bianchi-Marzoli, Stefania; Milesi, Jacopo; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

    2011-02-10

    We assessed abnormalities within the principal brain resting state networks (RSNs) in patients with Leber's hereditary optic neuropathy (LHON) to define whether functional abnormalities in this disease are limited to the visual system or, conversely, tend to be more diffuse. We also defined the structural substrates of fMRI changes using a connectivity-based analysis of diffusion tensor (DT) MRI data. Neuro-ophthalmologic assessment, DT MRI and RS fMRI data were acquired from 13 LHON patients and 13 healthy controls. RS fMRI data were analyzed using independent component analysis and SPM5. A DT MRI connectivity-based parcellation analysis was performed using the primary visual and auditory cortices, bilaterally, as seed regions. Compared to controls, LHON patients had a significant increase of RS fluctuations in the primary visual and auditory cortices, bilaterally. They also showed decreased RS fluctuations in the right lateral occipital cortex and right temporal occipital fusiform cortex. Abnormalities of RS fluctuations were correlated significantly with retinal damage and disease duration. The DT MRI connectivity-based parcellation identified a higher number of clusters in the right auditory cortex in LHON vs. controls. Differences of cluster-centroid profiles were found between the two groups for all the four seeds analyzed. For three of these areas, a correspondence was found between abnormalities of functional and structural connectivities. These results suggest that functional and structural abnormalities extend beyond the visual network in LHON patients. Such abnormalities also involve the auditory network, thus corroborating the notion of a cross-modal plasticity between these sensory modalities in patients with severe visual deficits.

  20. Extra-visual functional and structural connection abnormalities in Leber's hereditary optic neuropathy.

    Directory of Open Access Journals (Sweden)

    Maria A Rocca

    Full Text Available We assessed abnormalities within the principal brain resting state networks (RSNs in patients with Leber's hereditary optic neuropathy (LHON to define whether functional abnormalities in this disease are limited to the visual system or, conversely, tend to be more diffuse. We also defined the structural substrates of fMRI changes using a connectivity-based analysis of diffusion tensor (DT MRI data. Neuro-ophthalmologic assessment, DT MRI and RS fMRI data were acquired from 13 LHON patients and 13 healthy controls. RS fMRI data were analyzed using independent component analysis and SPM5. A DT MRI connectivity-based parcellation analysis was performed using the primary visual and auditory cortices, bilaterally, as seed regions. Compared to controls, LHON patients had a significant increase of RS fluctuations in the primary visual and auditory cortices, bilaterally. They also showed decreased RS fluctuations in the right lateral occipital cortex and right temporal occipital fusiform cortex. Abnormalities of RS fluctuations were correlated significantly with retinal damage and disease duration. The DT MRI connectivity-based parcellation identified a higher number of clusters in the right auditory cortex in LHON vs. controls. Differences of cluster-centroid profiles were found between the two groups for all the four seeds analyzed. For three of these areas, a correspondence was found between abnormalities of functional and structural connectivities. These results suggest that functional and structural abnormalities extend beyond the visual network in LHON patients. Such abnormalities also involve the auditory network, thus corroborating the notion of a cross-modal plasticity between these sensory modalities in patients with severe visual deficits.

  1. Sporadic diffuse segmental interstitial cell of Cajal hyperplasia harbouring two gastric gastrointestinal stromal tumours (GIST mimicking hereditary GIST syndromes

    Directory of Open Access Journals (Sweden)

    Mafalda Costa Neves

    2015-01-01

    Conclusion: We describe a diffuse form of sporadic ICC hyperplasia harbouring multifocal GISTs, mimicking diffuse ICC hyperplasia in hereditary GIST syndromes. Detection of somatic c-KIT exon 11 mutation ruled out a hereditary disorder.

  2. Gait Patterns in Patients with Hereditary Spastic Paraparesis

    Science.gov (United States)

    Ranavolo, Alberto; Lacquaniti, Francesco; Martino, Giovanni; Leonardi, Luca; Conte, Carmela; Varrecchia, Tiwana; Draicchio, Francesco; Coppola, Gianluca; Casali, Carlo; Pierelli, Francesco

    2016-01-01

    Background Spastic gait is a key feature in patients with hereditary spastic paraparesis, but the gait characterization and the relationship between the gait impairment and clinical characteristics have not been investigated. Objectives To describe the gait patterns in hereditary spastic paraparesis and to identify subgroups of patients according to specific kinematic features of walking. Methods We evaluated fifty patients by computerized gait analysis and compared them to healthy participants. We computed time-distance parameters of walking and the range of angular motion at hip, knee, and ankle joints, and at the trunk and pelvis. Lower limb joint moments and muscle co-activation values were also evaluated. Results We identified three distinct subgroups of patients based on the range of motion values. Subgroup one was characterized by reduced hip, knee, and ankle joint range of motion. These patients were the most severely affected from a clinical standpoint, had the highest spasticity, and walked at the slowest speed. Subgroup three was characterized by an increased hip joint range of motion, but knee and ankle joint range of motion values close to control values. These patients were the most mildly affected and had the highest walking speed. Finally, subgroup two showed reduced knee and ankle joint range of motion, and hip range of motion values close to control values. Disease severity and gait speed in subgroup two were between those of subgroups one and three. Conclusions We identified three distinctive gait patterns in patients with hereditary spastic paraparesis that correlated robustly with clinical data. Distinguishing specific features in the gait patterns of these patients may help tailor pharmacological and rehabilitative treatments and may help evaluate therapeutic effects over time. PMID:27732632

  3. Análisis Sensorial

    OpenAIRE

    Barris Vilor, Jacinto

    2010-01-01

    En nuestro caso queremos desarrollar un programa que nos facilite la labor de preparar las pruebas de los alimentos y su recogida de datos para el Laboratorio de la Fundación Miquel Agustí. En el laboratorio actualmente el análisis sensorial de los datos se obtiene a partir de análisis realizados por catadores entrenados en una sala especialmente diseñada para este tipo de análisis. Actualmente la toma de datos se realiza a través de unas fichas de cata en formato papel. ...

  4. Análisis Sensorial

    OpenAIRE

    Barris Vilor, Jacinto

    2010-01-01

    En nuestro caso queremos desarrollar un programa que nos facilite la labor de preparar las pruebas de los alimentos y su recogida de datos para el Laboratorio de la Fundación Miquel Agustí. En el laboratorio actualmente el análisis sensorial de los datos se obtiene a partir de análisis realizados por catadores entrenados en una sala especialmente diseñada para este tipo de análisis. Actualmente la toma de datos se realiza a través de unas fichas de cata en formato papel. ...

  5. Hereditary gingival fibromatosis with distinct dental, skeletal and developmental abnormalities.

    Science.gov (United States)

    Katz, Joseph; Guelmann, Marcio; Barak, Shlomo

    2002-01-01

    A case of a 9-year-old child with hereditary gingival fibromatosis, supernumerary tooth, chest deformities, auricular cartilage deformation, joint laxity and undescended testes is described. The exact mode of inheritance is unclear; a new mutation pattern is possible. These features resemble but differ from the previously reported Laband syndrome. The dental treatment consisted of surgical removal of the fibrous tissue and conservative restorative treatment under general anesthesia. The dental practitioner should be alert for developmental abnormalities such as supernumerary teeth and delayed tooth eruption. A comprehensive medical history and physical systemic evaluation is essential to rule out other systemic abnormalities. Genetic consultation is mandatory for future family planing.

  6. Moyamoya disease in a patient with hereditary spherocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Holz, A.; Woldenberg, R.; Miller, D.; Kalina, P.; Black, K.; Lane, E. [Department of Radiology, North Shore University Hospital, New York University School of Medicine, 300 Community Drive, Manhasset, NY 11030 (United States)

    1998-02-01

    Moyamoya disease (MMD) is a rare cerebral vasculopathy characterized by occlusion of the supraclinoid portion of the internal carotid artery and proximal portions of the anterior and middle cerebral arteries. Patients develop an extensive collateral network of parenchymal, transdural and leptomeningeal vessels to supply the compromised brain. These collateral channels, also known as ``moyamoya vessels,`` may be seen in a number of disorders which lead to intracranial vascular occlusion. We report a case of MMD in a child with hereditary spherocytosis. (orig.) With 4 figs., 5 refs.

  7. Leber’s hereditary optic neuropathy - case report

    Directory of Open Access Journals (Sweden)

    Mirjana A. Janicijevic Petrovic

    2012-09-01

    Full Text Available Leber’s hereditary optic neuropathy is a neuro-ophthalmological entity characterized by acute or subacute bilateral, not simultaneous visual loss with centro cekal scotoma and occasional further visual improvement. This rare ophthalmological disease can be accompanied with dyschromatopsia. It is associated with a matrilineal inheritance pattern. Its diagnosis used to be solely clini¬cal, aided by imaging and neuro-physiological studies, until the advent of descriptions of mitochondrial biochemical abnormalities and genetic testing. We describe a case of 24 year old male with progressive painless deterioration of visual acuity and positive family history.

  8. Mitochondrial DNA Mutation Associated with Leber's Hereditary Optic Neuropathy

    Science.gov (United States)

    Wallace, Douglas C.; Singh, Gurparkash; Lott, Marie T.; Hodge, Judy A.; Schurr, Theodore G.; Lezza, Angela M. S.; Elsas, Louis J.; Nikoskelainen, Eeva K.

    1988-12-01

    Leber's hereditary optic neuropathy is a maternally inherited disease resulting in optic nerve degeneration and cardiac dysrhythmia. A mitochondrial DNA replacement mutation was identified that correlated with this disease in multiple families. This mutation converted a highly conserved arginine to a histidine at codon 340 in the NADH dehydrogenase subunit 4 gene and eliminated an Sfa NI site, thus providing a simple diagnostic test. This finding demonstrated that a nucleotide change in a mitochondrial DNA energy production gene can result in a neurological disease.

  9. Current concepts in the treatment of hereditary ataxias

    Directory of Open Access Journals (Sweden)

    Pedro Braga Neto

    2016-03-01

    Full Text Available ABSTRACT Hereditary ataxias (HA represents an extensive group of clinically and genetically heterogeneous neurodegenerative diseases, characterized by progressive ataxia combined with extra-cerebellar and multi-systemic involvements, including peripheral neuropathy, pyramidal signs, movement disorders, seizures, and cognitive dysfunction. There is no effective treatment for HA, and management remains supportive and symptomatic. In this review, we will focus on the symptomatic treatment of the main autosomal recessive ataxias, autosomal dominant ataxias, X-linked cerebellar ataxias and mitochondrial ataxias. We describe management for different clinical symptoms, mechanism-based approaches, rehabilitation therapy, disease modifying therapy, future clinical trials and perspectives, genetic counseling and preimplantation genetic diagnosis.

  10. CDH1 germline mutations and hereditary lobular breast cancer.

    Science.gov (United States)

    Corso, Giovanni; Intra, Mattia; Trentin, Chiara; Veronesi, Paolo; Galimberti, Viviana

    2016-04-01

    Hereditary diffuse gastric cancer is an autosomal dominant inherited disease associated of CDH1 germline mutations (that encodes for the E-cadherin protein), and lobular breast cancer is the second most frequent type of neoplasia. Recently, novel E-cadherin constitutional alterations have been identified in pedigree clustering only for lobular breast carcinoma without evidence of diffuse gastric tumors and in absence of BRCA1/2 mutations. This first evidence opens novel questions about the inherited correlation between diffuse gastric and lobular breast cancers. In this brief review we revise the literature data about the CDH1 mutation frequency affecting exclusively lobular breast cancer, providing clinical recommendation for asymptomatic mutation carriers.

  11. Hereditary vitamin D-resistant rickets presenting as alopecia.

    Science.gov (United States)

    Casey, Genevieve; McPherson, Tess; Kini, Usha; Ryan, Fiona; Taibjee, Saleem M; Moss, Celia; Burge, Susan

    2014-01-01

    Hereditary vitamin D-resistant rickets (HVDRR) is a rare autosomal recessive disorder caused by mutations in the vitamin D receptor (VDR) gene. We report the case of an infant presenting with alopecia, growth failure, and gross motor developmental delay. Serum biochemistry and skeletal survey were consistent with rickets. After a poor response to standard treatment, genetic testing confirmed a c.147-2A>T novel mutation in the VDR gene consistent with HVDRR. It is important for dermatologists and pediatricians to recognize alopecia as a presenting sign of HVDRR because appropriate treatment leads to better growth and development of the child.

  12. Postangioedema attack skin blisters: an unusual presentation of hereditary angioedema.

    Science.gov (United States)

    Wiesen, Jonathan; Gonzalez-Estrada, Alexei; Auron, Moises

    2014-04-10

    Hereditary angioedema (HAE) is an autosomal dominant disorder characterised by attacks of self-limited swelling affecting extremities, face and intra-abdominal organs, most often caused by mutations in the C1-inhibitor gene with secondary Bradykinin-mediated increased vascular permeability. We describe a 36-year-old man with a history of HAE who presented with painful interdigital bullae secondary to an acute oedema exacerbation. Biopsy and cultures of the lesions were negative and they resolved spontaneously. It is important to highlight and recognise the development of oedema blisters after resolution of a flare of HAE (only 1 previous case report), and hence avoid unnecessary dermatological diagnostic workup and treatment.

  13. Atypical Leber Hereditary Optic Neuropathy: 18 Year Interval Between Eyes.

    Science.gov (United States)

    Ohden, Kaitlyn L; Tang, Peter H; Lilley, Chrystia C; Lee, Michael S

    2016-09-01

    A 5-year-old boy developed profound loss of vision in his right eye and was found to have a 11778 mitochondrial point mutation consistent with Leber hereditary optic neuropathy (LHON). He maintained 20/20 vision in the left eye for 18 years until age 23, when he experienced loss of vision in that eye. This 18 year interval between eye involvement in LHON is the longest reported to date and reinforces the variability in presentation and progression seen in this disease.

  14. Late-onset Leber hereditary optic neuropathy mimicking Susac's syndrome.

    Science.gov (United States)

    Zoccolella, Stefano; Petruzzella, Vittoria; Prascina, Francesco; Artuso, Lucia; Pacillo, Francesca; Dell'Aglio, Rosa; Avolio, Carlo; Delle Noci, Nicola; Attimonelli, Marcella; Specchio, Luigi Maria

    2010-12-01

    Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder characterized by bilateral painless optic atrophy and blindness. It usually occurs in young men in association with three major mutations in the mitochondrial genome (mtDNA). We report a patient with a history of alcohol abuse who developed at age 63 years visual impairment, sensorineural hearing loss, and memory dysfunction, suggestive of Susac's syndrome. The patient carried the heteroplasmic mt. 11778G>A mutation on the T2e mtDNA haplogroup. It remains unclear if chronic alcohol abuse combined with the mitochondrial genetic background prompted an aged-related neurodegeneration or deferred the onset of the LHON disease.

  15. Leber Hereditary Optic Neuropathy: Bringing the Lab to the Clinic.

    Science.gov (United States)

    Rasool, Nailyn; Lessell, Simmons; Cestari, Dean M

    2016-01-01

    Leber hereditary optic neuropathy (LHON) was the first clinically characterized mitochondrial disorder. Since its first description in 1871, much has been discovered regarding the genetics and pathophysiology of the disease. This has enabled the development of in vitro cell and animal models that can be used to try to determine not only the effects of the genetic mutation upon the clinical phenotype but to also test potential novel therapies. Treatments for LHON have ranged from vitamins and minerals to immunosuppressants and, more recently, targeted gene therapy. This article reviews the pathophysiology and clinical features of LHON with a focus on translational research.

  16. Mutation analysis in Turkish patients with hereditary fructose intolerance.

    Science.gov (United States)

    Dursun, A; Kalkanoğlu, H S; Coşkun, T; Tokatli, A; Bittner, R; Koçak, N; Yüce, A; Ozalp, I; Boehme, H J

    2001-10-01

    Thirteen Turkish patients with hereditary fructose intolerance (HFI) were screened for the three common mutations, A149P, A174D and N334K, in the aldolase B gene that have been detected frequently in European population. We found that nine of the patients carry the A149P mutation in both alleles, which corresponds to a frequency of about 55%. Single-strand conformation analysis of all coding exons of the gene was also performed to detect unknown mutations in four patients not carrying the three common mutations. No aberrant migration patterns were observed in these patients.

  17. Leber Hereditary Optic Neuropathy Associated with Bilateral Macular Holes

    Science.gov (United States)

    Shimada, Yoshiaki; Horiguchi, Masayuki

    2016-01-01

    ABSTRACT Leber hereditary optic neuropathy (LHON) causes visual loss, predominantly in healthy young men. We recently examined a patient who previously had bilateral macular holes and subsequently developed LHON at 74 years of age. Although his central scotomas were initially attributed to the macular holes, his visual acuity declined following an initial improvement after operative closure of the macular holes; thus, other diagnoses, including LHON, were considered. Furthermore, macular optical coherence tomography (OCT) images remained unchanged in this time. A mitochondrial genetic analysis identified a 11778G→A mutation. From this case, we propose that LHON remains in the differential diagnosis even in older patients, as has previously been reported. PMID:27335507

  18. [Organization of therapeutic aid to patients with hereditary neuromuscular diseases].

    Science.gov (United States)

    Kalinin, V A; Temin, P A; Arkhipov, B A; Zavadenko, N N

    1989-01-01

    The paper summarizes experience gained for many years by the All-Union Research Methodological Center for Study of Hereditary Neuromuscular Diseases. The specialists of the Center render counselling and therapeutic assistance to patients afflicted with neuromuscular diseases. The counselling and diagnostic services are characterized by the fact that it is based on the activity of a large hospital intended for the treatment of various diseases. The problems which are being solved by the out- and inpatient services of the Center are considered in detail. The advantages of the setting up of the common in- and outpatient complex on the basis of the hospital intended for the treatment of various diseases are described.

  19. Cannabis potentially reduces recurrent episodes of hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Phumpattra Chariyawong

    2017-01-01

    Full Text Available Hereditary angioedema (HAE is a rare disease affecting an estimated 1 in 50,000 individuals in the United States.The clinical presentation involves recurrent episodes of angioedema, without urticaria or pruritus, in mucosal tissues of various organ systems. We present a case of HAE type II with concomitant use of cannabis that possibly decreased the frequency of his episodes of angioedema. Recent studies indicate that cannabis has an important role in regulating innate immunity and inflammatory responses through the inhibition of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines. These effects might reduce episodes of angioedema, but more research is needed.

  20. [Hereditary angioedema. Control and treatment in 7 cases].

    Science.gov (United States)

    Marqués, L; Dordal, T; Baltasar, M; Guspi, R; Nogueiras, C; Cadahia, A

    1992-03-14

    Hereditary angioedema (HAE) is due to a deficit of the C1 inhibitor (C1 INH) of a dominant autosomic inheritance. Seven patients are presented from a family with HAE, four of whom with poor prognosis due to the frequency and site of the angioedema. Prophylaxis was obtained with long-term danazol since antifibrinolytic drugs are not efficient in the prevention of outbreaks of angioedema. In three cases a concentrate of C1 INH was administered and in another as short term prophylaxis prior to surgery. C1 INH was more efficient under these indications than fresh plasma or antifibrinolytic drugs.

  1. Hereditary properties of Amenability modulo an ideal of Banach algebras

    Directory of Open Access Journals (Sweden)

    Hamidreza Rahimi

    2014-10-01

    Full Text Available In this paper we investigate some hereditary properties of amenability modulo an ideal of Banach algebras. We show thatif $(e_{\\alpha}_{\\alpha}$ is a bounded approximate identity modulo $I$ of a Banach algebra $A$ and $X$ is a neo-unital modulo $I$, then $(e_{\\alpha}_{\\alpha}$ is a bounded approximate identity for $X$. Moreover we show that amenability modulo an ideal of a Banach algebra $A$ can be only considered by the neo-unital modulo $I$ Banach algebra over $A$

  2. Congenital optic nerve anomalies and hereditary optic neuropathies.

    Science.gov (United States)

    Heidary, Gena

    2014-12-01

    Congenital and hereditary optic nerve anomalies represent a significant cause of visual dysfunction. While some optic nerve abnormalities affect the visual system alone, others may be associated with neurologic and systemic findings. Correct identification of the optic nerve disease therefore is crucial both for developing a treatment plan with respect to visual rehabilitation, but also for initiating the appropriate multidisciplinary evaluation. The purpose of this review is to highlight common examples of congenital and inherited optic nerve abnormalities in an effort to familiarize the clinician with salient clinical features of these diseases and to review important systemic testing when relevant.

  3. Did Robert Louis Stevenson have hereditary hemorrhagic telangiectasia?

    Science.gov (United States)

    Guttmacher, A E; Callahan, J R

    2000-03-06

    Chronic illness played a major role in the life and literary success of Robert Louis Stevenson. However, the exact nature of his chronic illness remains unclear. It is possible that Stevenson had hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber Syndrome). This would explain his chronic respiratory complaints, recurrent episodes of pulmonary hemorrhage, and his death, at age 44 years, of probable cerebral hemorrhage. It would also explain his mother's hitherto unreported but apparent stroke, at age 38 years. Further support for this hypothesis might come from new details about the health of Stevenson and his relatives or from molecular analysis of tissue specimens remaining from him.

  4. Hereditary spastic paraplegia: clinical principles and genetic advances.

    Science.gov (United States)

    Fink, John K

    2014-07-01

    Hereditary spastic paraplegia (HSP) refers to inherited disorders in which spastic gait is either the only feature or is a major syndrome feature. There are more than 70 genetic types of HSP. Neuropathological studies, albeit limited to only a few genetic types of HSP, have identified axon degeneration involving the distal ends of the corticospinal tracts and fasciculus gracilis fibers. In this review, the author highlights the clinical and genetic features of HSP. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. Unchanged binding of /sup 99/Molybdenum to red cell membrane proteins in hereditary spherocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Marik, T.; Kselikova, M.; Bibr, B.; Brabec, V.; Lener, J. (Ceskoslovenska Akademie Ved, Prague. Ustav Nuklearni Biologie a Radiochemie; Institut Hygieny a Epidemiologie, Prague (Czechoslovakia))

    1983-01-01

    The interaction of /sup 99/Mo with red cell membrane proteins was found specific for spectrin both in normal red cells and those of hereditary spherocytosis. In addition, no significant quantitative differences were observed in labelling patterns between these two types of red cells, thus indicating no major alterations in the spectrin molecules of hereditary spherocytosis.

  6. A MELAS-associated ND1 mutation causing leber hereditary optic neuropathy and spastic dystonia.

    NARCIS (Netherlands)

    Spruijt, L.; Smeets, H.J.M.; Hendrickx, A.; Bettink-Remeijer, M.W.; Maat-Kievit, A.; Schoonderwoerd, K.C.; Sluiter, W.; Coo, I.F.M. de; Hintzen, R.Q.

    2007-01-01

    OBJECTIVE: To report a novel mutation that is associated with Leber hereditary optic neuropathy (LHON) within the same family affected by spastic dystonia. DESIGN: Leber hereditary optic neuropathy is a mitochondrial disorder characterized by isolated central visual loss. Of patients with LHON, 95%

  7. Estimation of EuroQol 5-Dimensions health status utility values in hereditary angioedema

    DEFF Research Database (Denmark)

    Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen;

    2016-01-01

    OBJECTIVE: To estimate health status utility (preference) weights for hereditary angioedema (HAE) during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe) survey. Utility measures quantitatively describe the net impact of a...

  8. Comprehensive mutational screening in a cohort of Danish families with hereditary congenital cataract

    DEFF Research Database (Denmark)

    Hansen, Lars; Mikkelsen, Annemette; Nürnberg, Peter

    2009-01-01

    PURPOSE: Identification of the causal mutations in 28 unrelated families and individuals with hereditary congenital cataract identified from a national Danish register of hereditary eye diseases. Seven families have been published previously, and the data of the remaining 21 families are presente...

  9. An effect from anticipation also in hereditary nonpolyposis colorectal cancer families without identified mutations

    DEFF Research Database (Denmark)

    Timshel, Susanne; Therkildsen, Christina; Bendahl, Pär-Ola

    2009-01-01

    Optimal prevention of hereditary cancer is central and requires initiation of surveillance programmes and/or prophylactic measures at a safe age. Anticipation, expressed as an earlier age at onset in successive generations, has been demonstrated in hereditary nonpolyposis colorectal cancer (HNPCC...

  10. A family with hereditary ankyloglossia complicated by heterochromia irides and a congenital clasped thumb.

    Science.gov (United States)

    Sato, T; Iida, M; Yamaguchi, Y

    1983-10-01

    We experienced a family with hereditary ankyloglossia complicated by heterochromia irides and a congenital clasped thumb. This is considered to be a rare case because, to our knowledge, there have been no published reports on such cases of hereditary complications to date.

  11. Surveillance for hereditary nonpolyposis colorectal cancer - A long-term study on 114 families

    NARCIS (Netherlands)

    Cappel, WHDTN; Nagengast, FM; Griffioen, G; Menko, FH; Taal, BG; Kleibeuker, JH; Vasen, HF

    2002-01-01

    PURPOSE: Hereditary nonpolyposis colorectal cancer is caused by germline mutations in DNA mismatch repair genes. Mutation carriers have a 60 to 85 percent risk of developing colorectal cancer. In the Netherlands hereditary nonpolyposis colorectal cancer families are monitored in an intensive

  12. A MELAS-associated ND1 mutation causing leber hereditary optic neuropathy and spastic dystonia.

    NARCIS (Netherlands)

    Spruijt, L.; Smeets, H.J.M.; Hendrickx, A.; Bettink-Remeijer, M.W.; Maat-Kievit, A.; Schoonderwoerd, K.C.; Sluiter, W.; Coo, I.F.M. de; Hintzen, R.Q.

    2007-01-01

    OBJECTIVE: To report a novel mutation that is associated with Leber hereditary optic neuropathy (LHON) within the same family affected by spastic dystonia. DESIGN: Leber hereditary optic neuropathy is a mitochondrial disorder characterized by isolated central visual loss. Of patients with LHON, 95%

  13. Estimation of EuroQol 5-Dimensions health status utility values in hereditary angioedema

    DEFF Research Database (Denmark)

    Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen

    2016-01-01

    OBJECTIVE: To estimate health status utility (preference) weights for hereditary angioedema (HAE) during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe) survey. Utility measures quantitatively describe the net impact of a...

  14. The Chemical Background for Sensory Quality

    DEFF Research Database (Denmark)

    Zhang, Shujuan

    In the food industry, high sensory quality and stability of products are crucial factors for consumer satisfaction and market shares. Sensory quality is normally being evaluated by two major approaches: instrumental (volatile and nonvolatile compounds) approach and sensory approach by trained...... or consumer panels. Sensory evaluation is a primary measurement for providing immediate information of human perception on the products. Instrumental methods give objective analysis of compounds that potentially contribute to food flavour. These two kinds of analysis, basically, give different types...... of information about food flavour but correlate to each other. The exploration of relationships between sensory and instrumental data is one important aspect for fundamental understanding of the mechanisms of sensory perception. This thesis has investigated the importance and limitation of aroma analysis...

  15. Multivariate analysis of data in sensory science

    CERN Document Server

    Naes, T; Risvik, E

    1996-01-01

    The state-of-the-art of multivariate analysis in sensory science is described in this volume. Both methods for aggregated and individual sensory profiles are discussed. Processes and results are presented in such a way that they can be understood not only by statisticians but also by experienced sensory panel leaders and users of sensory analysis. The techniques presented are focused on examples and interpretation rather than on the technical aspects, with an emphasis on new and important methods which are possibly not so well known to scientists in the field. Important features of the book are discussions on the relationship among the methods with a strong accent on the connection between problems and methods. All procedures presented are described in relation to sensory data and not as completely general statistical techniques. Sensory scientists, applied statisticians, chemometricians, those working in consumer science, food scientists and agronomers will find this book of value.

  16. Cognitive mechanisms associated with auditory sensory gating.

    Science.gov (United States)

    Jones, L A; Hills, P J; Dick, K M; Jones, S P; Bright, P

    2016-02-01

    Sensory gating is a neurophysiological measure of inhibition that is characterised by a reduction in the P50 event-related potential to a repeated identical stimulus. The objective of this work was to determine the cognitive mechanisms that relate to the neurological phenomenon of auditory sensory gating. Sixty participants underwent a battery of 10 cognitive tasks, including qualitatively different measures of attentional inhibition, working memory, and fluid intelligence. Participants additionally completed a paired-stimulus paradigm as a measure of auditory sensory gating. A correlational analysis revealed that several tasks correlated significantly with sensory gating. However once fluid intelligence and working memory were accounted for, only a measure of latent inhibition and accuracy scores on the continuous performance task showed significant sensitivity to sensory gating. We conclude that sensory gating reflects the identification of goal-irrelevant information at the encoding (input) stage and the subsequent ability to selectively attend to goal-relevant information based on that previous identification.

  17. Sensory quality criteria for five fish species

    DEFF Research Database (Denmark)

    Warm, Karin; Nielsen, Jette; Hyldig, Grethe;

    2000-01-01

    Sensory profiling has been used to develop one sensory vocabulary for five fish species: cod (Gadus morhua), saithe (Pollachius virens), rainbow trout (Salmo gardineri), herring (Clupea harengus) and flounder (Platichthys flessus). A nine- member trained panel assessed 18 samples with variation...... variation and by presenting references, panel discussions and interpreting plots from multivariate data analysis. The developed profile can be used as a sensory wheel for these species, and with minor changes it may be adapted to similar species...

  18. Experienced Sensory Modalities in Dream Recall

    OpenAIRE

    岡田, 斉

    2000-01-01

    The purpose of the present study is to survey the frequency of visual, auditory, kinaesthetic, cutaneous, organic, gustatory, and olfactory experience in dream recall. A total of 1267 undergraduate students completed a dream recall frequency questionnaire, which contained a question about dream recall frequency and about recall frequency of seven sensory modalities. Results showed that seven sensory modalities were divided into two groups; normally perceived sensory modalities in dreaming, wh...

  19. Sensorial evaluation of irradiated mangoes

    Energy Technology Data Exchange (ETDEWEB)

    Broisler, Paula Olhe; Cruz, Juliana Nunes da; Sabato, Susy Frey [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mails: paulabroisler@hotmail.com; juliananc@ig.com.br; sfsabato@ipen.br

    2007-07-01

    Mango (Mangifera indica L.) is a tropical fruit of great economical relevance in the world, mainly for tropical countries like Brazil. It consists in the second tropical fruit more important grown in the world. On the other hand it is a very perishable fruit and its delivery to distant points is restricted due to short shelf life at environmental temperature. Food irradiation process is applied to fruits for their preservation, once it promotes disinfestation and even maturation retard, among other mechanisms. The Brazilian legislation permits the food irradiation and does not restrict the doses to be delivered. In order to verify eventual changes, sensorial evaluation is very important to study how irradiation affects the quality of the fruit and its acceptability. Mangoes were irradiated in a Cobalto-60 source, from the Radiation Technology Center, CTR, of IPEN/CNEN-SP at doses 0,5 kGy e 0,75 kGy. The sensorial evaluation was measured through Acceptance Test where irradiated samples were offered together with control sample to the tasters who answered their perception through hedonic scale. The parameters Color, Odor, Flavor and Texture were analyzed. Statistical analysis showed that only Odor parameter was different from control (sample irradiated at 0.5 kGy). Few tasters indicated that irradiated mangoes had fewer odors in relation to non-irradiated samples. (author)

  20. A case of neuromyelitis optica harboring both anti-aquaporin-4 antibodies and a pathogenic mitochondrial DNA mutation for Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Shiraishi, Wataru; Hayashi, Shintaro; Kamada, Takashi; Isobe, Noriko; Yamasaki, Ryo; Murai, Hiroyuki; Ohyagi, Yasumasa; Kira, Jun-ichi

    2014-02-01

    We report the first case of definite neuromyelitis optica (NMO) with a pathogenic mitochondrial DNA (mtDNA) mutation for Leber's hereditary optic neuropathy (LHON) (G11778A point mutation). A 36-year-old Japanese woman had experienced recurrent neurological symptoms originating from involvements of the optic nerves and spinal cord. She finally lost her bilateral vision, and spastic paraparesis and sensory disturbances below the T6 level remained despite intensive immunotherapies. Brain and spinal magnetic resonance imaging (MRI) revealed T2-high-intensity lesions in the optic nerves and thoracic spinal cord, but no lesions in the brain. A blood examination revealed positivity for both anti-aquaproin-4 antibodies and an LHON mtDNA mutation.

  1. Prevalence of hereditary angioedema in untested first-degree blood relatives of known subjects with hereditary angioedema.

    Science.gov (United States)

    Riedl, Marc A; Lumry, William R; Busse, Paula; Levy, Howard; Steele, Tamara; Dayno, Jeffrey; Li, H Henry

    2015-01-01

    Hereditary angioedema (HAE) is a rare autosomal-dominant disease characterized by recurring attacks of nonpruritic, nonpitting edema caused by an inherited deficiency or dysfunction of C1 esterase inhibitor (C1 INH). Symptoms can present years before an accurate diagnosis is made. The objective of this study, the Angioedema Clinical Epidemiology Testing Initiative for the Study of Hereditary Angioedema, was to determine the prevalence and clinical manifestations of HAE in untested first-degree blood relatives of known patients with HAE. Patients with a confirmed diagnosis of HAE recruited first-degree relatives who had not been evaluated for HAE. Enrolled subjects underwent complement testing (C4, C1 INH antigen, and functional C1 INH). If the lab tests were abnormal, the enrolled subjects returned to the site for a follow-up visit and questionnaire. Overall, 31 patients with HAE and 46 first-degree relatives enrolled in the study. Of 46 enrolled relatives, 30 (65%) had lab test results that ruled out a diagnosis of HAE, two (4%) were categorized as "HAE not ruled out," and 14 (30%) were newly diagnosed with HAE. Of 14 newly diagnosed subjects, nine (64%) reported having experienced symptoms that may have been related to HAE, such as swelling in the throat, face, or extremities or abdominal pain. When reported, median age of symptom onset in these 14 subjects was nine years whereas newly diagnosed asymptomatic subjects had a median chronological age of six years. These 14 subjects reported a historic mean standard deviation rate of 2.51 (5.59) swelling episodes per month with a mean standard deviation duration of 1.6 (0.74) days. This study's findings reinforce the importance of testing family members of patients with HAE to detect this hereditary condition.

  2. [Acute Sensory Neuropathies and Acute Autonomic Neuropathies].

    Science.gov (United States)

    Koike, Haruki

    2015-11-01

    From the perspective of neuropathies with an acute onset mimicking that of Guillain-Barré syndrome (GBS), cases with profound sensory and/or autonomic impairment without any significant weakness have been reported. Although the possibility of infectious or toxic etiologies should be carefully excluded, immune mechanisms similar to those in GBS are suggested to be involved in these so-called acute sensory neuropathies and acute autonomic neuropathies. The types of neuropathy include those with predominant sensory manifestations, predominant autonomic manifestations such as autoimmune autonomic ganglionopathy, and both sensory and autonomic manifestations such as acute autonomic and sensory neuropathy. Neuronopathy in the sensory and/or autonomic ganglia (i.e., ganglionopathy) has been commonly suggested in patients with these types of neuropathies. The presence of Anti-GD1b antibodies has been reported in some of the patients with acute sensory neuropathy with deep sensory impairment, whereas anti-ganglionic acetylcholine receptor antibodies are reported to be present in half of the patients with autoimmune autonomic ganglionopathy. The discovery of anti-ganglionic acetylcholine receptor antibodies significantly expanded the spectrum of autoimmune autonomic ganglionopathy. This is because some of the patients with chronic progression mimicking neurodegenerative diseases such as pure autonomic failure were positive for these antibodies. In contrast, pathologically significant autoantibodies have not been identified in acute autonomic and sensory neuropathy. Further studies are needed to clarify the pathogenesis and the spectrum of these types of neuropathies.

  3. Overexpression of Sterol Carrier Protein 2 in Patients with Hereditary Cholesterol Gallstones

    Directory of Open Access Journals (Sweden)

    Zhang Ju

    2011-02-01

    Full Text Available Abstract Background Lithogenic bile is the major cause of cholesterol gallstone, but its pathogenesis is not well understood. The hypersecretion of biliary cholesterol is believed to be an important cause of lithogenic bile. Sterol Carrier Protein 2 (SCP2 participates in cholesterol trafficking and lipid metabolism in hepatocytes and may play a key role in cholesterol gallstone formation. Methods 21 cholesterol gallstone genealogies were studied to investigate the expression of SCP2 gene in liver tissue of hereditary and non-hereditary cholesterol gallstone patients as well as non-gallstone patients. The mRNA expression of liver SCP2 in 28 hereditary patients, 30 non-hereditary cholesterol gallstone patients and 32 non-gallstone patients was measured by Reverse Transcription Polymerase Chain Reaction (RT-PCR. The protein expression of liver SCP2 was also detected in all the patients by Western blotting. At the same time, the bile was also analyzed with biochemical techniques and the Cholesterol Saturation Index (CSI was calculated. Results The mRNA and protein expression of SCP2 was significantly increased in cholesterol gallstone patients compared to those of non-gallstone patients. Moreover, SCP2 was expressed at higher levels in hereditary cholesterol gallstone patients than that of non-hereditary cholesterol gallstone patients. There was significant difference observed in CSI between cholesterol gallstone patients and non-gallstone patients, but not in CSI between hereditary and non-hereditary cholesterol gallstone patients. Conclusions SCP2 was overexpressed in hereditary cholesterol gallstone patients compared to non-hereditary cholesterol gallstone patients. This finding indicated that SCP2 might be one of the genetic factors contributing to cholesterol gallstone formation, which was always accompanied by the increase of bile lithogenicity.

  4. Sensory and motor deficits in children with cerebral palsy born preterm correlate with diffusion tensor imaging abnormalities in thalamocortical pathways

    Science.gov (United States)

    HOON, ALEXANDER H; STASHINKO, ELAINE E; NAGAE, LIDIA M; LIN, DORIS DM; KELLER, JENNIFER; BASTIAN, AMY; CAMPBELL, MICHELLE L; LEVEY, ERIC; MORI, SUSUMU; JOHNSTON, MICHAEL V

    2010-01-01

    AIM Cerebral palsy (CP) is frequently linked to white matter injury in children born preterm. Diffusion tensor imaging (DTI) is a powerful technique providing precise identification of white matter microstructure. We investigated the relationship between DTI-observed thalamocortical (posterior thalamic radiation) injury, motor (corticospinal tract) injury, and sensorimotor function. METHOD Twenty-eight children born preterm(16 males, 12 females; mean age 5y 10mo, SD 2y 6mo, range 16mo–13y; mean gestational age at birth 28wks, SD 2.7wks, range 23–34wks) were included in this case–control study. Twenty-one children had spastic diplegia, four had spastic quadriplegia, two had hemiplegia, and one had ataxic hypotonic CP; 15 of the participants walked independently. Normative comparison data were obtained from 35 healthy age-matched children born at term(19 males, 16 females; mean age 5y 9mo, SD 4y 4mo, range 15mo–15y). Two-dimensional DTI color maps were created to evaluate 26 central white matter tracts, which were graded by a neuroradiologist masked to clinical status. Quantitative measures of touch, proprioception, strength (dynamometer), and spasticity (modified Ashworth scale) were obtained from a subset of participants. RESULTS All 28 participants with CP had periventricular white-matter injury on magnetic resonance imaging. Using DTI color maps, there was more severe injury in the posterior thalamic radiation pathways than in the descending corticospinal tracts. Posterior thalamic radiation injury correlated with reduced contralateral touch threshold, proprioception, and motor severity, whereas corticospinal tract injury did not correlate with motor or sensory outcome measures. INTERPRETATION These findings extend previous research demonstrating that CP in preterm children reflects disruption of thalamocortical connections as well as descending corticospinal pathways. PMID:19416315

  5. Antimyosin scintigraphy in patients with acquired and hereditary muscular disorders

    Energy Technology Data Exchange (ETDEWEB)

    Loefberg, M. (Dept. of Neurology, Helsinki Univ. Central Hospital (Finland)); Liewendahl, K. (Dept. of Clinical Chemistry, Helsinki Univ. Central Hospital (Finland)); Savolainen, S. (Dept. of Clinical Chemistry, Helsinki Univ. Central Hospital (Finland)); Nikkinen, P. (Dept. of Clinical Chemistry, Helsinki Univ. Central Hospital (Finland)); Lamminen, A. (Dept. of Radiology, Helsinki Univ. Central Hospital (Finland)); Tiula, E. (First Dept. of Internal Medicine, Helsinki Univ. Central Hospital (Finland)); Somer, H. (Dept. of Neurology, Helsinki Univ. Central Hospital (Finland))

    1994-10-01

    Scintigraphy with indium-111 labelled antimyosin has an established role in the evaluation of cardiac muscle damage. This antibody has been shown to cross-react with myosin in skeletal muscle. We therefore studied the usefulness of this method for the detection of skeletal muscle lesions in rhabdomyolysis, myositis and hereditary muscular dystrophies. All nine patients with rhabdomyolysis had focal uptake of antimyosin antibody which correlated with the clinical findings of soft tissue damage. However, a number of symptomless lesions were also detected by immunoscintigraphy. In rhabdomyolysis the target to non-target uptake ratios varied from 1.3 to 7.6. Diffuse uptake of antibody in skeletal muscle was observed in all three patients with polymyositis-dermatomyositis and in 12 out of 13 patients with muscular dystrophies. In myositis the intensity of antibody accumulation correlated reasonably well with the magnitude of oedema detected by magnetic resonance imaging (MRI). Most patients with Becker type or non-X-chromosomal muscular dystrophies showed slight or moderate uptake of antibody, mainly in the lower extremities. In these patients more antibody accumulated in the calves than in the thighs, whereas the findings on MRI were more prominent in the thighs than in the calves, presumably because of the better preserved muscle bulk in the calves. We conclude that antimyosin scintigraphy can be used for the detection of muscle lesions not only in acquired muscle diseases but also in hereditary muscular disorders, and that immunoscintigraphy provides information on muscle disease activity not obtainable with MRI. (orig.)

  6. Studies on four hereditary blood disorders in Iceland

    Energy Technology Data Exchange (ETDEWEB)

    Jensson, O.

    1978-01-01

    An Icelandic family with fifty elliptocytic individuals is reviewed. Pedigree studies indicate strongly that affected members of the family are descendants of a common ancestor. The hereditary pattern is typical of a dominant autosomal gene with full penetrance. Thirty members with typical hereditary spherocytosis (HS) and over 70 apparently unaffected members belonging to 12 families have been studied. Pedigree studies on one of the families indicate that the HS gene or genes have been transmitted through six generations over the past 200 years. Much reduced penetrance of the HS gene or the presence of the so-called mild form is upheld as the main explanation for the unevenness in the genetic ratio. An Icelandic family containing fourteen members with Pelger anomaly is reviewed. It is possible that this family is the only one with this type of mutation in Icelanders. Genealogical information indicates that the Pelger anomaly gene has been present in this family over 200 years. Three families with Von Willebrand's disease (VW) are reviewed. Severe symptoms of bleeding predominate in the males, two of whom have died from hemorrhage. There is a reduced expressivity of the mutant gene, amounting to nonpenetrance, mainly in the female members of the families. It is thought probable that the mutant gene present in the three families has originated from a common ancestor in a district which is common to the three families. (KRM)

  7. Pediatric hereditary angioedema due to C1-inhibitor deficiency

    Directory of Open Access Journals (Sweden)

    Farkas Henriette

    2010-07-01

    Full Text Available Abstract Hereditary angioedema (HAE resulting from the deficiency of the C1 inhibitor (C1-INH is a rare, life-threatening disorder. It is characterized by attacks of angioedema involving the skin and/or the mucosa of the upper airways, as well as the intestinal mucosa. In approximately 50 per cent of cases, clinical manifestations may appear during childhood. The complex management of HAE in pediatric patients is in many respects different from the management of adults. Establishing the diagnosis early, preferably before the onset of clinical symptoms, is essential in cases with a positive family history. Complement studies usually afford accurate diagnosis, whereas molecular genetics tests may prove helpful in uncertain cases. Appropriate therapy, supported by counselling, suitable modification of lifestyle, and avoidance of triggering factors (which primarily include mechanical trauma, mental stress and airway infections in children may spare the patient unnecessary surgery and may prevent mortality. Prompt control of edematous attacks, short-term prophylaxis and intermittent therapy are recommended as the primary means for the management of pediatric cases. Medicinal products currently used for the treatment of children with hereditary angioedema include antifibrinolytics, attenuated androgens, and C1-INH replacement therapy. Current guidelines favour antifibrinolytics for long-term prophylaxis because of their favorable safety profile but efficacy may be lacking. Attenuated androgens administered in the lowest effective dose are another option. C1-INH replacement therapy is also an effective and safe agent for children. Regular monitoring and follow-up of patients are necessary.

  8. Hereditary hemochromatosis and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Ellervik, Christina; Tybjaerg-Hansen, Anne; Grande, Peer;

    2005-01-01

    BACKGROUND: We tested the hypothesis that the hereditary hemochromatosis genotypes C282Y/C282Y, C282Y/H63D, or C282Y/wild-type are risk factors for ischemic heart disease (IHD) and myocardial infarction (MI). METHODS AND RESULTS: We performed a prospective study of 9178 individuals from the Danish...... risk of IHD or MI in prospective studies, overall or stratified by gender. We had 90% power to detect a hazard ratio for IHD of 3.4 for C282Y/C282Y, 1.9 for C282Y/H63D, and 1.3 for C282Y/wild-type versus wild-type/wild-type. Furthermore, these genotypes were not associated with increased risk of IHD...... or MI in case-control studies, overall or stratified by gender. We had 90% power to detect an odds ratio for IHD of 3.6 for C282Y/C282Y, 1.8 for C282Y/H63D, and 1.3 for C282Y/wild-type versus wild-type/wild-type. CONCLUSIONS: In these studies, hereditary hemochromatosis C282Y/C282Y, C282Y/H63D, and C282...

  9. Hereditary apolipoprotein AI-associated renal amyloidosis: A diagnostic challenge.

    Science.gov (United States)

    Samillán-Sosa, Kelly Del Rocío; Sención-Martínez, Gloria; Lopes-Martín, Vanessa; Martínez-González, Miguel Angel; Solé, Manel; Arostegui, Jose Luis; Mesa, Jose; García-Díaz, Juan de Dios; Rodríguez-Puyol, Diego; Martínez-Miguel, Patricia

    2015-01-01

    Hereditary renal amyloidosis is an autosomal dominant condition with considerable overlap with other amyloidosis types. Differential diagnosis is complicated, but is relevant for prognosis and treatment. We describe a patient with nephrotic syndrome and progressive renal failure, who had a mother with renal amiloidosis. Renal biopsy revealed amyloid deposits in glomerular space, with absence of light chains and protein AA. We suspected amyloidosis with fibrinogen A alpha chain deposits, which is the most frequent cause of hereditary amyloidosis in Europe, with a glomerular preferential affectation. However, the genetic study showed a novel mutation in apolipoprotein AI. On reviewing the biopsy of the patient's mother similar glomerular deposits were found, but there were significant deposits in the renal medulla as well, which is typical in APO AI amyloidosis. The diagnosis was confirmed by immunohistochemistry. Apo AI amyloidosis is characterized by slowly progressive renal disease and end-stage renal disease occurs aproximately 3 to 15 years from initial diagnosis. Renal transplantation offers an acceptable graft survival and in these patients with hepatorenal involvement simultaneous liver and kidney transplantation could be considered. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

  10. Molecular and genetic characteristics of hereditary autoinflammatory diseases.

    Science.gov (United States)

    Tunca, Mehmet; Ozdogan, Huri

    2005-02-01

    Autoinflammatory diseases are defined as recurrent "unprovoked" inflammatory events which do not produce high-titer autoantibodies or antigen-specific T cells. There are currently eight hereditary forms of these diseases: Familial Mediterranean fever (FMF), hyperimmunoglobulinemia D with periodic fever syndrome (HIDS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), chronic infantile neurologic cutaneous articular (CINCA) syndrome or neonatal-onset multisystem inflammatory disease (NOMID), pyogenic sterile arthritis, pyoderma gangrenosum, acne (PAPA) and Blau syndrome. Apart from FMF (which has a prevalence of about 0.1 percent among non-Ashkenazi Jews, Armenians, Turks and Arabs), they are very rare disorders. FMF and HIDS are autosomal recessive diseases, all the other members of the family are autosomal and dominantly transmitted. Their common clinical features are recurrent and usually short attacks of synovitis and various skin eruptions; abdominal pain and fever are also frequently observed. The genes of all of these diseases have been discovered and, with the exception of HIDS, it was found that the proteins they encode share certain domains taking part in innate immunity and apoptosis. Thus it was evident that hereditary autoinflammatory diseases may help us understand better a number of important and prevalent pathologic events. We have reviewed the recent and rapidly accumulating knowledge on the molecular aspects of these disorders.

  11. Hyper-IgD syndrome and hereditary periodic fever syndromes

    Directory of Open Access Journals (Sweden)

    L. Vicentini

    2011-09-01

    Full Text Available Hereditary periodic fever syndromes are a group of systemic disorders characterized by recurrent attacks of systemic inflammation (autoinflammation without infectious or autoimmune cause. The hyper-IgD syndrome (HIDS is a rare autosomal recessive inflammatory disorder characterized by recurrent fever, increased serum IgD (normal value < 100 U/ml and generalized inflammation (lymphadenopathy, arthralgias/arthritis, abdominal complaints, skin rash, and headache. The attacks persist during the entire life although frequency and severity tend to diminish with age. HIDS is caused by specific mutations in the gene encoding mevalonate kinase, resulting in depressed enzymatic activity. At present the therapy for the syndrome is only supportive. Other than HIDS, other hereditary systemic inflammatory disorders have been described: the Familial Mediterranean Fever, the tumour necrosis factor receptor associated periodic syndrome (TRAPS, a disease related to the mutations of one of the TNF receptors, the Familial Cold Urticaria and the Muckle-Wells syndrome. The differential diagnosis with other causes of periodic fever is crucial for assessing appropriate management and treatment.

  12. Generation of plasmin during acute attacks of hereditary angioedema.

    Science.gov (United States)

    Cugno, M; Hack, C E; de Boer, J P; Eerenberg, A J; Agostoni, A; Cicardi, M

    1993-01-01

    Hereditary angioedema is caused by a genetic deficiency of C1-inhibitor, a serine protease inhibitor that regulates activation of complement, contact, and fibrinolytic systems. Symptoms (bouts of subcutaneous and mucous swelling) depend on the release of a vasoactive mediator, probably through activation of these three systems. We studied the interrelationship among complement, contact, and fibrinolytic activation in 23 patients with hereditary angiodema, 18 during remission and five during an attack, by measuring plasma levels of C1-C1 inhibitor, factor XIIa-C1 inhibitor, kallikrein-C1 inhibitor, and plasmin-alpha 2-antiplasmin complexes, tissue plasminogen activator, and urokinase plasminogen activator. In addition, cleavage of high-molecular weight kininogen was detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis and quantified by densitometry. During remission, plasma levels of C1-C1 inhibitor complexes were elevated (p = 0.0002), whereas the other parameters were within the normal range. During acute attacks, not only plasma levels of C1-C1 inhibitor complexes but also those of plasmin-alpha 2-antiplasmin complexes (P = 0.0009) and cleaved high-molecular weight kininogen were elevated. A positive correlation between plasmin-alpha 2-antiplasmin complexes and cleaved high-molecular weight kininogen was observed (r = 0.75, p attacks is associated with the activation of the fibrinolytic system.

  13. Progressive cerebellar atrophy: hereditary ataxias and disorders with spinocerebellar degeneration.

    Science.gov (United States)

    Wolf, Nicole I; Koenig, Michel

    2013-01-01

    The hereditary ataxias with onset in childhood are a group of heterogeneous disorders, usually with autosomal recessive inheritance. In many of them, magnetic resonance imaging (MRI) shows cerebellar atrophy. The most prominent exception to this is Friedreich's ataxia, where MRI shows normal cerebellar volume, but sometimes spinal cord atrophy. In several of the hereditary ataxias, the causative gene plays an important role in DNA repair: ataxia telangiectasia and ataxia telangiectasia-like disorder, and ataxia with oculomotor apraxia type I and II. Mitochondrial metabolism is impaired in another group of inherited ataxias including the emergent group of defects in coenzyme Q10 synthesis. Few of these disorders are amenable to effective treatment, the most important of these being vitamin E-responsive ataxia. The autosomal dominant spinocerebellar ataxias are rare in childhood. Some of them, especially SCA7 and SCA2, may begin in childhood or even infancy, family history being positive in these cases. Additional clinical clues such as presence or absence of neuropathy or oculomotor apraxia still help in making a definitive diagnosis albeit there are still many unsolved cases. In pontocerebellar hypoplasia, a neurodegenerative disease with prenatal onset, the genetic basis of the different subtypes has recently been elucidated and involves genes with different functions.

  14. Targeted high throughput sequencing in hereditary ataxia and spastic paraplegia

    Science.gov (United States)

    Koht, Jeanette; Pihlstrøm, Lasse; Rengmark, Aina H.; Henriksen, Sandra P.; Tallaksen, Chantal M. E.; Toft, Mathias

    2017-01-01

    Hereditary ataxia and spastic paraplegia are heterogeneous monogenic neurodegenerative disorders. To date, a large number of individuals with such disorders remain undiagnosed. Here, we have assessed molecular diagnosis by gene panel sequencing in 105 early and late-onset hereditary ataxia and spastic paraplegia probands, in whom extensive previous investigations had failed to identify the genetic cause of disease. Pathogenic and likely-pathogenic variants were identified in 20 probands (19%) and variants of uncertain significance in ten probands (10%). Together these accounted for 30 probands (29%) and involved 18 different genes. Among several interesting findings, dominantly inherited KIF1A variants, p.(Val8Met) and p.(Ile27Thr) segregated in two independent families, both presenting with a pure spastic paraplegia phenotype. Two homozygous missense variants, p.(Gly4230Ser) and p.(Leu4221Val) were found in SACS in one consanguineous family, presenting with spastic ataxia and isolated cerebellar atrophy. The average disease duration in probands with pathogenic and likely-pathogenic variants was 31 years, ranging from 4 to 51 years. In conclusion, this study confirmed and expanded the clinical phenotypes associated with known disease genes. The results demonstrate that gene panel sequencing and similar sequencing approaches can serve as efficient diagnostic tools for different heterogeneous disorders. Early use of such strategies may help to reduce both costs and time of the diagnostic process. PMID:28362824

  15. Guidelines for the genetic diagnosis of hereditary recurrent fevers

    DEFF Research Database (Denmark)

    Shinar, Y; Obici, L; Aksentijevich, I

    2012-01-01

    Hereditary recurrent fevers (HRFs) are a group of monogenic autoinflammatory diseases characterised by recurrent bouts of fever and serosal inflammation that are caused by pathogenic variants in genes important for the regulation of innate immunity. Discovery of the molecular defects responsible ...... and 19 September 2011 to ratify the draft and obtain a final consensus document. An agreed set of best practice guidelines was proposed for genetic diagnostic testing of HRFs, for reporting the genetic results and for defining their clinical significance.......Hereditary recurrent fevers (HRFs) are a group of monogenic autoinflammatory diseases characterised by recurrent bouts of fever and serosal inflammation that are caused by pathogenic variants in genes important for the regulation of innate immunity. Discovery of the molecular defects responsible...... for these diseases has initiated genetic diagnostics in many countries around the world, including the Middle East, Europe, USA, Japan and Australia. However, diverse testing methods and reporting practices are employed and there is a clear need for consensus guidelines for HRF genetic testing. Draft guidelines were...

  16. Sensory Sensitivities and Performance on Sensory Perceptual Tasks in High-Functioning Individuals with Autism

    Science.gov (United States)

    Minshew, Nancy J.; Hobson, Jessica A.

    2008-01-01

    Most reports of sensory symptoms in autism are second hand or observational, and there is little evidence of a neurological basis. Sixty individuals with high-functioning autism and 61 matched typical participants were administered a sensory questionnaire and neuropsychological tests of elementary and higher cortical sensory perception. Thirty-two…

  17. PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

    Science.gov (United States)

    2014-01-01

    PMP22 related neuropathies comprise (1) PMP22 duplications leading to Charcot-Marie-Tooth disease type 1A (CMT1A), (2) PMP22 deletions, leading to Hereditary Neuropathy with liability to Pressure Palsies (HNPP), and (3) PMP22 point mutations, causing both phenotypes. Overall prevalence of CMT is usually reported as 1:2,500, epidemiological studies show that 20-64% of CMT patients carry the PMP22 duplication. The prevalence of HNPP is not well known. CMT1A usually presents in the first two decades with difficulty walking or running. Distal symmetrical muscle weakness and wasting and sensory loss is present, legs more frequently and more severely affected than arms. HNPP typically leads to episodic, painless, recurrent, focal motor and sensory peripheral neuropathy, preceded by minor compression on the affected nerve. Electrophysiological evaluation is needed to determine whether the polyneuropathy is demyelinating. Sonography of the nerves can be useful. Diagnosis is confirmed by finding respectively a PMP22 duplication, deletion or point mutation. Differential diagnosis includes other inherited neuropathies, and acquired polyneuropathies. The mode of inheritance is autosomal dominant and de novo mutations occur. Offspring of patients have a chance of 50% to inherit the mutation from their affected parent. Prenatal testing is possible; requests for prenatal testing are not common. Treatment is currently symptomatic and may include management by a rehabilitation physician, physiotherapist, occupational therapist and orthopaedic surgeon. Adult CMT1A patients show slow clinical progression of disease, which seems to reflect a process of normal ageing. Life expectancy is normal. PMID:24646194

  18. PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies.

    Science.gov (United States)

    van Paassen, Barbara W; van der Kooi, Anneke J; van Spaendonck-Zwarts, Karin Y; Verhamme, Camiel; Baas, Frank; de Visser, Marianne

    2014-03-19

    PMP22 related neuropathies comprise (1) PMP22 duplications leading to Charcot-Marie-Tooth disease type 1A (CMT1A), (2) PMP22 deletions, leading to Hereditary Neuropathy with liability to Pressure Palsies (HNPP), and (3) PMP22 point mutations, causing both phenotypes. Overall prevalence of CMT is usually reported as 1:2,500, epidemiological studies show that 20-64% of CMT patients carry the PMP22 duplication. The prevalence of HNPP is not well known. CMT1A usually presents in the first two decades with difficulty walking or running. Distal symmetrical muscle weakness and wasting and sensory loss is present, legs more frequently and more severely affected than arms. HNPP typically leads to episodic, painless, recurrent, focal motor and sensory peripheral neuropathy, preceded by minor compression on the affected nerve. Electrophysiological evaluation is needed to determine whether the polyneuropathy is demyelinating. Sonography of the nerves can be useful. Diagnosis is confirmed by finding respectively a PMP22 duplication, deletion or point mutation. Differential diagnosis includes other inherited neuropathies, and acquired polyneuropathies. The mode of inheritance is autosomal dominant and de novo mutations occur. Offspring of patients have a chance of 50% to inherit the mutation from their affected parent. Prenatal testing is possible; requests for prenatal testing are not common. Treatment is currently symptomatic and may include management by a rehabilitation physician, physiotherapist, occupational therapist and orthopaedic surgeon. Adult CMT1A patients show slow clinical progression of disease, which seems to reflect a process of normal ageing. Life expectancy is normal.

  19. Sensory Metrics of Neuromechanical Trust.

    Science.gov (United States)

    Softky, William; Benford, Criscillia

    2017-09-01

    that individuals can improve sensory and sociosensory resolution through deliberate sensory reintegration practices. We conclude that we humans are the victims of our own success, our hands so skilled they fill the world with captivating things, our eyes so innocent they follow eagerly.

  20. Multisensory integration, sensory substitution and visual rehabilitation

    DEFF Research Database (Denmark)

    Proulx, Michael J; Ptito, Maurice; Amedi, Amir

    2014-01-01

    Sensory substitution has advanced remarkably over the past 35 years since first introduced to the scientific literature by Paul Bach-y-Rita. In this issue dedicated to his memory, we describe a collection of reviews that assess the current state of neuroscience research on sensory substitution...