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Sample records for hereditary angioedema subjects

  1. 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 of this re...... 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....

  2. 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 of r...

  3. Genetics Home Reference: hereditary angioedema

    Science.gov (United States)

    ... named? Additional Information & Resources MedlinePlus (2 links) Encyclopedia: Hereditary angioedema Health Topic: Vascular Diseases Genetic and Rare Diseases Information Center (1 link) Hereditary ...

  4. 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.

  5. 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.

  6. 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 how...... of hereditary angioedema. The case illustrates how clinicians can have difficulties in handling patients with rare diseases, especially in the emergency care setting....

  7. 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...

  8. How we manage persons with hereditary angioedema

    National Research Council Canada - National Science Library

    Zuraw, Bruce L; Christiansen, Sandra C

    2016-01-01

    Hereditary angioedema ( HAE ) is a rare autosomal dominant genetic disorder clinically characterized by recurrent attacks of subcutaneous and mucosal swelling that can result in significant morbidity and even mortality...

  9. Disease expression in women with hereditary angioedema

    DEFF Research Database (Denmark)

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

    2008-01-01

    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...... 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...... improved it for 64%. During pregnancies, 38% of women had more attacks, but 30% had fewer attacks. Vaginal delivery was usually uncomplicated. Attacks occurred within 48 hours in only 6% of cases. Those more severely affected during menses had more symptoms during pregnancies, suggesting a hormone...

  10. [Hereditary angioedema: strange cause of abdominal pain].

    Science.gov (United States)

    Salas-Lozano, Nereo Guillermo; Meza-Cardona, Javier; González-Fernández, Coty; Pineda-Figueroa, Laura; de Ariño-Suárez, Mauricio

    2014-01-01

    Hereditary angioedema is an episodic swelling disorder with autosomal dominant inheritance characterized by sudden attacks of peripheral swelling. Patients also commonly have episodic swelling of the wall of hollow viscera, including the bowel. We present a 33-year-old previously healthy male with a complaint of acute-onset intense abdominal pain localized in the epigastrium. Pain irradiated to the right lower quadrant and was associated with five episodes of vomiting. Computed tomography showed thickening of the duodenal wall with liquid in the subphrenic space. Complementary laboratory tests showed low C4 complement levels (5.5 mg/dl) and 30% complement C1 inhibitor activity. Hereditary angioedema is caused by a deficiency (type I) or dysfunction (type II) in complement C1 inhibitor. Abdominal associated with angioedema may manifest as severe acute-onset abdominal pain or as moderately severe chronic recurrent abdominal pain. Two medications are currently FDA-approved for the treatment of these patients.

  11. 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...

  12. Epidemiology of Non-hereditary Angioedema

    DEFF Research Database (Denmark)

    Madsen, Flemming; Attermann, Jorn; 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...

  13. Pathogenesis and laboratory diagnosis of hereditary angioedema.

    Science.gov (United States)

    Zuraw, Bruce L; Christiansen, Sandra C

    2009-01-01

    Hereditary angioedema (HAE) was first described in the 19th century. Over the past 50 years, many details of the pathophysiology and molecular biology of HAE have been elucidated. Two types of HAE, type I and type II, result from mutations in the gene for the broad-spectrum protease inhibitor C1 inhibitor (C1INH). Type I HAE is characterized by low antigenic and functional C1INH levels and type II HAE has normal antigenic but low functional C1INH levels. Type III HAE, by contrast, has normal antigenic and functional C1INH levels. In some families, type III HAE has been linked to mutations in Hageman factor. C1INH is the primary inhibitor of the complement proteases C1r and C1s as well as the contact system proteases activated Hageman factor (coagulation factor XIIa and XIIf) and plasma kallikrein. It is also an inhibitor of plasmin and coagulation factor XIa. The primary mediator of swelling in HAE has now been unequivocally shown to be bradykinin, generated from activation of the plasma contact system. The knowledge gained concerning the underlying mechanisms of the different types of HAE allow the clinician to approach the laboratory diagnosis with confidence and provides opportunities for novel therapeutic strategies.

  14. An ABC of the Warning Signs of Hereditary Angioedema

    DEFF Research Database (Denmark)

    Grumach, Anete Sevciovic; Ferraroni, Natasha; Olivares, Maria Margarita

    2017-01-01

    Hereditary angioedema (HAE) with C1 inhibitor deficiency is a genetic disorder that clinically manifests with attacks of angioedema in the subcutaneous and submucosal tissues, mainly in the extremities, abdomen, and upper airway. During attacks, vascular permeability is increased due to increased.......e., the so-called “ABC” of the warning signs of HAE. The letters represent the following: A = Angioedema, B = Bradykinin, C = C1 inhibitor, D = Distress factors, E = Epinephrine nonresponsive, F = Family history, and G = Glottis/Gastrointestinal edema. To avoid fatalities, medical staff and patients...

  15. New treatments addressing the pathophysiology of hereditary angioedema.

    Science.gov (United States)

    Davis, Alvin E

    2008-04-14

    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 attacks; the nano-filtered C1

  16. Safety and Usage of C1-Inhibitor in Hereditary Angioedema

    DEFF Research Database (Denmark)

    Riedl, Marc A; Bygum, Anette; Lumry, William

    2016-01-01

    BACKGROUND: The plasma-derived, highly purified, nanofiltered C1-inhibitor concentrate (Berinert; "pnfC1-INH") is approved in the United States for treating hereditary angioedema (HAE) attacks and in many European countries for attack treatment and short-term prophylaxis. OBJECTIVE: The objective...... of this study was to describe safety and usage patterns of pnfC1-INH. METHODS: A multicenter, observational, registry was conducted between 2010 and 2014 at 30 United States and 7 European sites to obtain both prospective (occurring after enrollment) and retrospective (occurring before enrollment) safety...... and usage data on subjects receiving pnfC1-INH for any reason. RESULTS: Of 343 enrolled patients, 318 received 1 or more doses of pnfC1-INH for HAE attacks (11,848 infusions) or for prophylaxis (3142 infusions), comprising the safety population. Median dosages per infusion were 10.8 IU/kg (attack treatment...

  17. Benefits and risks of danazol in hereditary angioedema

    DEFF Research Database (Denmark)

    Bork, Konrad; Bygum, Anette; Hardt, Jochen

    2008-01-01

    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...

  18. Prevalence of autoantibodies in a group of hereditary angioedema patients Prevalência de autoanticorpos em uma população com angioedema hereditário

    OpenAIRE

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

    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 par...

  19. Angioedema hereditario en pediatría Hereditary pediatric angioedema

    OpenAIRE

    A. Calvo Gómez-Rodulfo; J.E. García López; J.D. Herrero-Morín; G. Rodríguez García; F. González Guerra

    2009-01-01

    Introducción: El angioedema hereditario es una patología de origen genético causada por la alteración del gen que codifica la proteína inhibidora de la C1 esterasa activada (C1-INH). La prevalencia de esta entidad es baja, lo que dificulta su diagnóstico y manejo adecuado.
    Caso clínico: Se presenta el caso de una paciente con episodios repetidos de edema subcutáneo localizado en las extremidades desde los tres años de vida, añadiendo disfagia y disfonía a partir de la pu...

  20. Hereditary angioedema type I: a case report

    Directory of Open Access Journals (Sweden)

    Francisca Muñoz Peralta

    2016-03-01

    Full Text Available El angioedema hereditario es una enfermedad rara, de gran heterogeneidad en los síntomas, manifestándose con edema a nivel cutáneo, mucosa gastrointestinal y de laringe/faringe. Aunque existen tres variedades, el tipo I es el más frecuente y es provocado por una deficiencia en la síntesis del complemento C1 inhibidor. La gravedad de la clínica, junto a la baja prevalencia de la enfermedad y la necesidad de un tratamiento específico, hacen que el diagnóstico y tratamiento de dicha patología sea aún una asignatura pendiente para el médico de familia en atención primaria. Presentamos el caso de un adolescente varón con déficit de α-1 antitripsina desde los seis meses de edad, con aparición de angioedemas en piernas y brazos a los 11 años, diagnosticado de angioedema hereditario tipo I un año después. El diagnóstico definitivo de la enfermedad permitió instaurar un tratamiento adecuado a su patología, que consiste en la prevención de brotes que puedan comprometer la vida del paciente y, en el caso de que aparezcan, en la administración del complemento C1 inhibidor.

  1. The role of the complement system in hereditary angioedema.

    Science.gov (United States)

    Csuka, Dorottya; Veszeli, Nóra; Varga, Lilian; Prohászka, Zoltán; Farkas, Henriette

    2017-09-01

    Hereditary angioedema (HAE) is a rare, but potentially life-threatening disorder, characterized by acute, recurring, and self-limiting edematous episodes of the face, extremities, trunk, genitals, upper airways, or the gastrointestinal tract. HAE may be caused by the deficiency of C1-inhibitor (C1-INH-HAE) but another type of the disease, hereditary angioedema with normal C1-INH function (nC1-INH-HAE) was also described. The patient population is quite heterogeneous as regards the location, frequency, and severity of edematous attacks, presenting large intra- and inter-individual variation. Here, we review the role of the complement system in the pathomechanism of HAE and also present an overview on the complement parameters having an importance in the diagnosis or in predicting the severity of HAE. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. 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.

  3. 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...

  4. Angioedema

    Science.gov (United States)

    Angioneurotic edema; Welts; Allergic reaction - angioedema; Hives - angioedema ... Angioedema may be caused by an allergic reaction . During the ... The body releases histamine when the immune system detects a ...

  5. Association of celiac disease and hereditary angioedema due to C1-inhibitor deficiency. Screening patients with hereditary angioedema for celiac disease: is it worth the effort?

    Science.gov (United States)

    Csuka, Dorottya; Kelemen, Zsuzsanna; Czaller, Ibolya; Molnár, Katalin; Füst, George; Varga, Lilian; Rajczy, Katalin; Szabó, Zsófia; Miklós, Kata; Bors, András; Farkas, Henriette

    2011-03-01

    Hereditary angioedema due to C1-inhibitor deficiency is a life-threatening condition, which manifests as edematous attacks involving subcutaneous tissues and/or the upper airway/gastrointestinal mucosa. Celiac disease is a gluten-sensitive small intestinal disorder that can lead to severe villous atrophy, malabsorption, and malignancy. Both hereditary angioedema and celiac disease may present with abdominal symptoms. Our aim was to study the occurrence of celiac disease in the hereditary angioedema population, as well as to analyze the clinical course of cases with both diseases. One hundred and twenty-eight patients with hereditary angioedema were screened for celiac disease, using serological methods [antiendomysial antibodies-immunoglobulin A (IgA), antiendomysial antibodies-IgG and tissue transglutaminase-IgA, tissue transglutaminase-IgG]. Clinical data of a child with hereditary angioedema and celiac disease diagnosed earlier were added to the dataset to be analyzed. Thus, the total number of patients was 129, comprising 107 adults and 22 pediatric patients. In patients with celiac disease, molecular genetics analysis (human leukocyte antigen-DQA1, human leukocyte antigen-DQB1) was carried out along with the introduction of a gluten-free diet and regular follow-up. Four out of the 22 children were diagnosed with celiac disease in our hereditary angioedema population. The prevalence of celiac disease among our pediatric patients with hereditary angioedema (22 children) was higher than in the general population (18.1 vs. 1.2%). Switching from the wheat starch-containing tranexamic acid product to danazol and introducing a gluten-free diet mitigated abdominal symptoms of hereditary angioedema. Similarities between the symptoms of hereditary angioedema and celiac disease may cause difficulties in differential diagnosis, as well as in choosing the appropriate therapy. In our opinion, screening hereditary angioedema patients for celiac disease is warranted if

  6. [Prophylactic use of icatibant before tracheal intubation of a patient with hereditary angioedema type III. (A literature review of perioperative management of patients with hereditary angioedema type III)].

    Science.gov (United States)

    Iturri Clavero, F; González Uriarte, A; Tamayo Medel, G; Gamboa Setién, P M

    2014-01-01

    Type III hereditary angioedema is a rare familial disorder that has recently been described as a separate condition. Triggers for episodes of angioedema include surgery, dental procedures, and tracheal intubation maneuvers. Since episodes affecting the upper airway are potentially life-threatening, prophylactic treatment is recommended in these situations. The use of icatibant (Firazyr(®)), for prevention of angioedema prior to tracheal intubation, is reported in a patient with type iii hereditary angioedema. A literature review on the anesthetic management of this condition was conducted. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  7. Functional C1-inhibitor diagnostics in hereditary angioedema: assay evaluation and recommendations

    DEFF Research Database (Denmark)

    Wagenaar-Bos, Ineke G A; Drouet, Christian; Aygören-Pursun, Emel

    2008-01-01

    Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. The most widespread underlying genetic deficiency is a heterozygous deficiency of the serine protease inhibitor C1 esterase inhibitor (C1-Inh). In addition ...

  8. Disease-modifying factors in hereditary angioedema: an RNA expression-based screening

    National Research Council Canada - National Science Library

    López-Lera, Alberto; Cabo, Fátima Sánchez; Garrido, Sofía; Dopazo, Ana; López-Trascasa, Margarita

    2013-01-01

    Hereditary Angioedema due to C1-Inhibitor deficiency (HAE types I and II) is a monogenic disease characterized by sudden, self-limited episodes of cutaneous and mucosal swelling due to local deregulation of vascular permeability...

  9. Hereditary angioedema: what the gastroenterologist needs to know

    Directory of Open Access Journals (Sweden)

    Ali MA

    2014-11-01

    Full Text Available M Aamir Ali, Marie L Borum Division of Gastroenterology and Liver Diseases, George Washington University, Washington, DC, USA Abstract: Up to 93% of patients with hereditary angioedema (HAE experience recurrent abdominal pain. Many of these patients, who often present to emergency departments, primary care physicians, general surgeons, or gastroenterologists, are misdiagnosed for years and undergo unnecessary testing and surgical procedures. Making the diagnosis of HAE can be challenging because symptoms and attack locations are often inconsistent from one episode to the next. Abdominal attacks are common and can occur without other attack locations. An early, accurate diagnosis is central to managing HAE. Unexplained abdominal pain, particularly when accompanied by swelling of the face and extremities, suggests the diagnosis of HAE. A family history and radiologic imaging demonstrating edematous bowel also support an HAE diagnosis. Once HAE is suspected, C4 and C1 esterase inhibitor (C1-INH laboratory studies are usually diagnostic. Patients with HAE may benefit from recently approved specific treatments, including plasma-derived C1-INH or recombinant C1-INH, a bradykinin B2-receptor antagonist, or a kallikrein inhibitor as first-line therapy and solvent/detergent-treated or fresh frozen plasma as second-line therapy for acute episodes. Short-term or long-term prophylaxis with nanofiltered C1-INH or attenuated androgens will prevent or reduce the frequency and severity of episodes. Gastroenterologists can play a critical role in identifying and treating patients with HAE, and should have a high index of suspicion when encountering patients with recurrent, unexplained bouts of abdominal pain. Given the high rate of abdominal attacks in HAE, it is important for gastroenterologists to appropriately diagnose and promptly recognize and treat HAE, or refer patients with HAE to an allergist. Keywords: hereditary angioedema, abdominal pain, diagnosis

  10. Diagnosis and management of hereditary angioedema: an emergency medicine perspective.

    Science.gov (United States)

    Moellman, Joseph J; Bernstein, Jonathan A

    2012-08-01

    Hereditary angioedema (HAE) is a rare and often debilitating condition associated with substantial morbidity and mortality in the absence of appropriate intervention. An underlying deficiency in functional C1-inhibitor (C1-INH) protein induces a vulnerability to unchecked activation of the complement, contact, and coagulation/fibrinolytic systems. The clinical consequence is a pattern of recurring attacks of non-pitting, non-pruritic edema, the urgency of which varies by the affected site. Laryngeal edema can escalate rapidly to asphyxiation, and severe cases of abdominal swelling can lead to hypovolemic shock. This report reviews the emergency diagnosis and treatment of hereditary angioedema and the impact of recently introduced treatments on treatment in the United States. Until recently, emergency physicians in the United States were hindered by the lack of rapidly effective treatment options for HAE attacks. In this article, general clinical and laboratory diagnostic procedures are reviewed against the backdrop of two case studies: one patient presenting with a known history of HAE and one with previously undiagnosed HAE. In many countries outside the United States, plasma-derived C1-INH concentrate has for decades been the first-line treatment for acute attacks. The end of 2009 ushered in a new era in the pharmacologic management of HAE attacks in the United States with the approval of two new treatment options for acute treatment: a plasma-derived C1-INH concentrate and a kallikrein inhibitor. With access to targeted and effective treatments, emergency physicians are now better equipped for successful and rapid intervention in urgent HAE cases. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Bowen Tom

    2010-07-01

    Full Text Available 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/Réseau Canadien d'angioédème héréditaire (RCAH http://www.haecanada.com and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus 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 an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management.

  12. Prevalence of autoantibodies in a group of hereditary angioedema patients Prevalência de autoanticorpos em uma população com angioedema hereditário

    Directory of Open Access Journals (Sweden)

    Sergio Duarte Dortas Junior

    2012-04-01

    Full Text Available 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.O Angioedema Hereditário é uma doença autossômica dominante. A pesquisa de rotina para autoanticorpos não é recomendada para pacientes com Angioedema Hereditário; entretanto, a prevalência desses anticorpos em pacientes com Angioedema Hereditário não está bem documentada. Objetivamos determinar a prevalência de autoanticorpos para identificar indivíduos sob risco de desenvolver doenças autoimunes. Quinze pacientes com Angioedema Hereditário atendidos no Hospital Universitário Clementino Fraga Filho aceitaram participar do estudo. A prevalência de autoanticorpos foi de 40%. Nossos dados indicam alta prevalência de autoanticorpos em pacientes com Angioedema Hereditário. Estudos de maior escala deveriam ser considerados para determinar a significância desses autoanticorpos no acompanhamento clínico de pacientes com Angioedema Hereditário.

  13. [Hereditary angioedema in Medellín (Colombia): Clinical evaluation and quality of life appraisal].

    Science.gov (United States)

    Sánchez, María Dulfary; Cuervo, Julián; Rave, Deisi; Clemen, Gustavo; Yepes-Núñez, Juan José; Ortiz-Reyes, Blanca; Sus, Sara; Cardona, Ricardo

    2015-01-01

    Hereditary angioedema is an autosomal dominant primary immunodeficiency caused by a deficiency of the C1 inhibitor protein and characterized by recurrent episodes of subcutaneous and mucosal edema. Unpredictable and frequent crisis of angioedema affect the quality of life of individuals suffering this kind of disorder. To analyze the clinical characteristics of a family with an index case of hereditary angioedema and to determine the impact of this disease on their quality of life. Twenty six members of the family were included in the trial; 25 of them were analyzed for C4 complement and antigenic and functional C1 inhibitor blood levels. Two instruments (SF-365 and KIDSCREEN-27) were used to evaluate adult health quality and children and teenagers quality of life, respectively. Eighty three percent (83%) of individuals reporting symptoms of the condition exhibited serological criteria of hereditary angioedema type I: low levels of both C4 complement and quantitative (antigenic) and qualitative (functional) C1 inhibitor. In relation to patients' psychological and emotional performance, their quality of life was significantly affected by the symptoms of hereditary angioedema. This study provides evidence of the first family in Valle de Aburrá (Colombia) characterized as having hereditary angioedema type I. Despite the use of a generic instrument, the negative impact on the quality of life of individuals suffering this disease was also confirmed.

  14. Management of upper airway edema caused by hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Farkas Henriette

    2010-07-01

    Full Text Available Abstract Hereditary angioedema is a rare disorder with a genetic background involving mutations in the genes encoding C1-INH and of factor XII. Its etiology is unknown in a proportion of cases. Recurrent edema formation may involve the subcutis and the submucosa - the latter can produce obstruction in the upper airways and thereby lead to life-threatening asphyxia. This is the reason for the high, 30-to 50-per-cent mortality of undiagnosed or improperly managed cases. Airway obstruction can be prevented through early diagnosis, meaningful patient information, timely recognition of initial symptoms, state-of-the-art emergency therapy, and close monitoring of the patient. Prophylaxis can substantially mitigate the risk of upper airway edema and also improve the patients' quality of life. Notwithstanding the foregoing, any form of upper airway edema should be regarded as a potentially life-threatening condition. None of the currently available prophylactic modalities is capable of preventing UAE with absolute certainty.

  15. Complement factor C4 activation in patients with hereditary angioedema

    DEFF Research Database (Denmark)

    Åbom, Anne; Bygum, Anette; Koch, Claus

    2017-01-01

    Objectives: Low complement factor C4 is usually considered a valuable screening tool for patients with the potentially life-threatening hereditary angioedema with C1-inhibitor (C1-INH) deficiency (C1-INH-HAE). However, there are patients with C1-INH-HAE presenting with normal C4 levels. This means......, that C1-INH-HAE may potentially be overlooked, if screening is performed only by measurement of C4. It has been suggested that measurement of C4 activation products is better suited to avoid false negative results. Our aim was to investigate whether total antigenic C4 or non-functional C4c is a better...... measure of the increased C4 activation in C1-INH-HAE patients. Design and methods: Two different monoclonal antibodies (mAb) to human C4 were produced: one had specificity for the β-chain of C4 and would thus react with both functional and non-functional C4, and the other was developed against the factor...

  16. Angioedema hereditario: Guía de tratamiento Hereditary angioedema: A therapeutic guide

    Directory of Open Access Journals (Sweden)

    Alejandro Malbrán

    2012-04-01

    Full Text Available El angioedema hereditario (HAE es una enfermedad rara, autosómica dominante, caracterizada por episodios que comprometen la piel, el tracto gastrointestinal y la laringe. Tiene una mortalidad histórica por asfixia del 15 al 50%. Es producida por la deficiencia funcional del C1 inhibidor. La identificación de la bradiquinina como mediador principal ha estimulado el desarrollo de nuevos medicamentos para tratar la enfermedad. El tratamiento del HAE se establece en consensos internacionales. El desarrollo de guías para el tratamiento de la enfermedad permite ordenar el uso de procedimientos diagnósticos y drogas. Describimos aquí algunas características farmacológicas de los medicamentos utilizados en el tratamiento del HAE en la Argentina: el concentrado plasmático de C1 inhibidor, el antagonista de la bradiquinina, icatibant, el andrógeno atenuado danazol y los agentes anti-fibrinolíticos ácidos épsilon aminocaproico (EACA y tranexámico. Asimismo, se describe su forma de uso y del control de los eventos adversos más frecuentes, así como las recomendaciones del último consenso internacional, aplicables para conformar una primera guía de tratamiento del HAE en la Argentina.Hereditary angioedema (HAE is a rare autosomal dominant disease, characterized by episodes of edema involving the skin, gastrointestinal tract and larynx. HAE has a historical asphyxia mortality of 15% to 50%. It is the consequence of functional C1 inhibitor deficiency. The identification of bradykinin as the principal mediator of the disease has lead to the development of new drugs for its treatment. HAE management and treatment are agreed by international consensus decision. A therapeutic guide for the treatment of the disease is important to improve diagnosis and treatment. We here describe the pharmacology of drugs available for the treatment of HAE in Argentina: plasma derived C1 Inhibitor, the bradykinin antagonist: icatibant, the attenuated androgen

  17. Hereditary angioedema type III (estrogen-dependent) report of three cases and literature review*

    OpenAIRE

    Miranda, Amanda Rodrigues; de Ue, Ana Paula Fusel; Sabbag, Dominique Vilarinho; Furlani, Wellington de Jesus; de Souza, Patr?cia Karla; Rotta, Osmar

    2013-01-01

    In this article, three cases of hereditary angioedema (HAE) type III (estrogen-dependent or with normal C1 inhibitor) are reported. The HAE was initially described in women of the same family in association with high-leveled estrogenic conditions such as the use of oral contraceptives and pregnancy. There is no change in the C1 inhibitor as happens in other types of hereditary angioedema, and mutations are observed in the encoding gene of the XII factor of coagulation in several patients. The...

  18. Hereditary angioedema: Assessing the hypothesis for underlying autonomic dysfunction.

    Science.gov (United States)

    Wu, Maddalena A; Casella, Francesco; Perego, Francesca; Suffritti, Chiara; Afifi Afifi, Nada; Tobaldini, Eleonora; Zanichelli, Andrea; Cogliati, Chiara; Montano, Nicola; Cicardi, Marco

    2017-01-01

    Attacks of Hereditary Angioedema due to C1-inhibitor deficiency (C1-INH-HAE)are often triggered by stressful events/hormonal changes. Our study evaluates the relationship between autonomic nervous system (ANS) and contact/complement system activation. Twenty-three HAE patients (6 males, mean age 47.5±11.4 years) during remission and 24 healthy controls (8 males, mean age 45.3±10.6 years) were studied. ECG, beat-by-beat blood pressure, respiratory activity were continuously recorded during rest (10') and 75-degrees-head-up tilt (10'). C1-INH, C4, cleaved high molecular weight kininogen (cHK) were assessed; in 16 patients and 11 controls plasma catecholamines were also evaluated. Spectral analysis of heart rate variability allowed extraction of low-(LF) and high-(HF) frequency components, markers of sympathetic and vagal modulation respectively. HAE patients showed higher mean systolic arterial pressure (SAP) than controls during both rest and tilt. Tilt induced a significant increase in SAP and its variability only in controls. Although sympathetic modulation (LFnu) increased significantly with tilt in both groups, LF/HF ratio, index of sympathovagal balance, increased significantly only in controls. At rest HAE patients showed higher noradrenaline values (301.4±132.9 pg/ml vs 210.5±89.6pg/ml, p = 0.05). Moreover, in patients tilt was associated with a significant increase in cHK, marker of contact system activation (49.5 ± 7.5% after T vs 47.1 ± 7.8% at R, p = 0.01). Our data are consistent with altered ANS modulation in HAE patients, i.e. increased sympathetic activation at rest and blunted response to orthostatic challenge. Tilt test-induced increased HK cleavage suggests a link between stress and bradykinin production.

  19. Hereditary angioedema: Assessing the hypothesis for underlying autonomic dysfunction.

    Directory of Open Access Journals (Sweden)

    Maddalena A Wu

    Full Text Available Attacks of Hereditary Angioedema due to C1-inhibitor deficiency (C1-INH-HAEare often triggered by stressful events/hormonal changes.Our study evaluates the relationship between autonomic nervous system (ANS and contact/complement system activation.Twenty-three HAE patients (6 males, mean age 47.5±11.4 years during remission and 24 healthy controls (8 males, mean age 45.3±10.6 years were studied. ECG, beat-by-beat blood pressure, respiratory activity were continuously recorded during rest (10' and 75-degrees-head-up tilt (10'. C1-INH, C4, cleaved high molecular weight kininogen (cHK were assessed; in 16 patients and 11 controls plasma catecholamines were also evaluated. Spectral analysis of heart rate variability allowed extraction of low-(LF and high-(HF frequency components, markers of sympathetic and vagal modulation respectively.HAE patients showed higher mean systolic arterial pressure (SAP than controls during both rest and tilt. Tilt induced a significant increase in SAP and its variability only in controls. Although sympathetic modulation (LFnu increased significantly with tilt in both groups, LF/HF ratio, index of sympathovagal balance, increased significantly only in controls. At rest HAE patients showed higher noradrenaline values (301.4±132.9 pg/ml vs 210.5±89.6pg/ml, p = 0.05. Moreover, in patients tilt was associated with a significant increase in cHK, marker of contact system activation (49.5 ± 7.5% after T vs 47.1 ± 7.8% at R, p = 0.01.Our data are consistent with altered ANS modulation in HAE patients, i.e. increased sympathetic activation at rest and blunted response to orthostatic challenge. Tilt test-induced increased HK cleavage suggests a link between stress and bradykinin production.

  20. The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency

    DEFF Research Database (Denmark)

    Csuka, Dorottya; Munthe-Fog, Lea; Skjoedt, Mikkel-Ole

    2013-01-01

    Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) causes disturbances in the complement system. However, the influence of HAE-C1-INH on the lectin pathway of complement is unresolved. Thus, we studied the main initiator molecules, enzymes and regulators in the lectin pathway...... in patients with HAE-C1-INH....

  1. Safety of C1-Esterase Inhibitor in Acute and Prophylactic Therapy of Hereditary Angioedema

    DEFF Research Database (Denmark)

    Busse, Paula; Bygum, Anette; Edelman, Jonathan

    2014-01-01

    BACKGROUND: The plasma-derived, pasteurized C1-inhibitor (C1-INH) concentrate, Berinert has a 4-decade history of use in hereditary angioedema (HAE), with a substantial literature base that demonstrates safety and efficacy. Thromboembolic events have rarely been reported with C1-INH products, typ...

  2. Guideline for Hereditary Angioedema (HAE 2010 by the Japanese Association for Complement Research - Secondary Publication

    Directory of Open Access Journals (Sweden)

    Takahiko Horiuchi

    2012-01-01

    Full Text Available This guideline was provided by the Japanese Association for Complement Research targeting clinicians for making an accurate diagnosis of hereditary angioedema (HAE, and for prompt treatment of the HAE patient in Japan. This is a 2010 year version and will be updated according to any pertinent medical advancements.

  3. Presence of C1-Inhibitor Polymers in a Subset of Patients Suffering from Hereditary Angioedema

    DEFF Research Database (Denmark)

    Elenius Madsen, Daniel; Hansen, Søren Werner Karlskov; Gram, Jørgen Brodersen

    2014-01-01

    Hereditary angioedema (HAE) is a potentially life-threatening disease caused by mutations in the gene encoding the serine protease inhibitor (serpin) C1 inhibitor (C1-inh). The mutations cause decreased functional plasma levels of C1-inh, which triggers unpredictable recurrent edema attacks...

  4. The hereditary angioedema burden of illness study in Europe (HAE-BOIS- Europe)

    DEFF Research Database (Denmark)

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

    2012-01-01

    ABSTRACT: BACKGROUND: Hereditary angioedema (HAE) is a rare but serious disease marked by swelling attacks in the extremities, face, trunk, airway, or abdominal areas that can be spontaneous or the result of trauma and other triggers. It can be life-threatening due to the risk of asphyxiation...

  5. Pediatric Hereditary Angioedema as a Cause of Acute Compartment Syndrome of the Hand and Forearm: A Case Report.

    Science.gov (United States)

    Venditto, Chelsea; Jager, Zachary; LoGiudice, John; Matloub, Hani

    2017-05-01

    Compartment syndrome of the upper extremity is a surgical emergency that, when left untreated, can have dire consequences. Its causes are numerous, one of which is the uncommon entity hereditary angioedema, an autosomal dominant disease resulting in edema in a variety of potential locations, including the extremities. This is only the second time hereditary angioedema has been mentioned in the literature as a cause of compartment syndrome. We present a case of hereditary angioedema leading to hand and forearm compartment syndrome in a 13-year-old pediatric patient. Diagnosis of hereditary angioedema was made by our Rheumatology colleagues with physical exam and a thorough history, and confirmed by laboratory studies. Our patient presented with compartment syndrome of the hand and forearm and underwent hand and volar forearm fasciotomies. She was subsequently worked up for hereditary angioedema with laboratory results confirming the diagnosis. She was discharged after a 5-day hospitalization with prophylactic C1-inhibitor therapy. Hereditary angioedema is a rare but known cause of compartment syndrome of the upper extremity, and must be considered when patients present with compartment syndrome of unknown etiology. This disease can be diagnosed by laboratory studies and symptoms can be controlled with medical therapy.

  6. Hepatocellular Carcinoma in a Noncirrhotic Liver after Long-Term Use of Danazol for Hereditary Angioedema

    Directory of Open Access Journals (Sweden)

    Soraya Rahal

    2014-12-01

    Full Text Available We report a 57-year-old male who was treated with high-dose danazol for hereditary angioedema for more than 30 years; he developed hepatocellular carcinoma in the absence of cirrhosis. Despite surgical resection, he had a recurrence and received sorafenib, but had a poor skin tolerance. Such tumors arising after danazol are infrequent, and this case is highly unique due to the minor lesions found on the liver.

  7. Endocan: A Novel Marker of Endothelial Dysfunction in C1-Inhibitor-Deficient Hereditary Angioedema.

    Science.gov (United States)

    Demirturk, Mustafa; Akpinar, Timur Selcuk; Kose, Murat; Gelincik, Aslı; Colakoğlu, Bahattin; Buyukozturk, Suna

    2017-10-24

    Hereditary angioedema (HAE) related to C1-inhibitor deficiency is a rare autosomal dominant disorder. Vascular cell adhesion molecules (VCAM) are known as endothelial activation markers. Endocan (also called ESM-1) is proposed as an endothelial dysfunction indicator. We aimed to investigate endothelial activation in attack-free periods in HAE patients by measuring their levels of endocan and VCAM-1. Twenty-six HAE patients (22 female, mean age 40 ± 13 years) and 38 healthy control patients (13 female, mean age 36.9 ± 12 years) were included in the study. Peripheral blood samples were collected from HAE patients during symptom-free periods and control subjects. Endocan and VCAM-1 levels were measured using the enzyme-linked immunosorbent assay method. The median serum levels of endocan (647 ± 101 ng/mL) and VCAM-1 (500 ± 79 ng/mL) in the HAE patients were significantly higher than in the control patients (391 ± 41 and 325 ± 4; p < 0.001 for both). The increased endocan and VCAM-1 levels may reflect an endothelial activation even in attack-free periods in HAE patients. © 2017 S. Karger AG, Basel.

  8. Successful C1 inhibitor short-term prophylaxis during redo mitral valve replacement in a patient with hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Coleman Suzanne

    2010-10-01

    Full Text Available Abstract Hereditary angioedema is characterized by sudden episodes of nonpitting edema that cause discomfort and pain. Typically the extremities, genitalia, trunk, gastrointestinal tract, face, and larynx are affected by attacks of swelling. Laryngeal swelling carries significant risk for asphyxiation. The disease results from mutations in the C1 esterase inhibitor gene that cause C1 esterase inhibitor deficiency. Attacks of hereditary angioedema result from contact, complement, and fibrinolytic plasma cascade activation, where C1 esterase inhibitor irreversibly binds substrates. Patients with hereditary angioedema cannot replenish C1 esterase inhibitor levels on pace with its binding. When C1 esterase inhibitor is depleted in these patients, vasoactive plasma cascade products cause swelling attacks. Trauma is a known trigger for hereditary angioedema attacks, and patients have been denied surgical procedures because of this risk. However, uncomplicated surgeries have been reported. Appropriate prophylaxis can reduce peri-operative morbidity in these patients, despite proteolytic cascade and complement activation during surgical trauma. We report a case of successful short-term prophylaxis with C1 esterase inhibitor in a 51-year-old man with hereditary angioedema who underwent redo mitral valve reconstructive surgery.

  9. Mutational spectrum and phenotypes in Danish families with hereditary angioedema because of C1 inhibitor deficiency

    DEFF Research Database (Denmark)

    Bygum, A; Fagerberg, C R; Ponard, D

    2011-01-01

    Hereditary angioedema (HAE), type I and II, is an autosomal dominant disease with deficiency of functional C1 inhibitor protein causing episodic swellings of skin, mucosa and viscera. HAE is a genetically heterogeneous disease with more than 200 different mutations in the SERPING1 gene. A genotype......-phenotype relationship does not seem to exist in HAE, although the polymorphism c.-21T>C of exon 2 has been reported to be associated with a more severe phenotype. We aimed to establish the mutational spectrum of C1 inhibitor deficiency in Denmark and investigate the possible disease-aggravating effect of the c.-21T...

  10. Estimation of EuroQol 5-Dimensions health status utility values in hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Aygören-Pürsün E

    2016-09-01

    Full Text Available Emel Aygören-Pürsün,1 Anette Bygum,2 Kathleen Beusterien,3 Emily Hautamaki,4 Zlatko Sisic,5 Henrik B Boysen,6 Teresa Caballero7 1Angioedema Centre, Department for Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt, Germany; 2Hereditary Angioedema Centre Denmark, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark; 3Outcomes Research Strategies in Health, Washington, DC, 4Patient Reported Outcomes, Oxford Outcomes Inc., an ICON plc company, Bethesda, MD, USA; 5ViroPharma Incorporated, Chatsworth House, Maidenhead, UK; 6HAEi – Hereditary Angioedema International Patient Organization for C1 Inhibitor Deficiencies, Skanderborg, Denmark; 7Allergy Department, Hospital La Paz Institute for Health Research (IdiPaz, Biomedical Research Network on Rare Diseases U754 (CIBERER, University Hospital La Paz, Madrid, Spain 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 condition on a patient’s life; a score of 0.0 reflects death and 1.0 reflects full health.Study design and methods: The HAE-BOIS-Europe was a cross-sectional survey conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective. Survey items that overlapped conceptually with the EuroQol 5-Dimensions (EQ-5D domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey for acute attacks and between attacks.Results: Overall, a total of 111 HAE-BOIS-Europe participants completed all selected survey items and thus allowed for computation

  11. Treatment of hereditary angioedema due to C1 inhibitor deficiency in Argentina

    Directory of Open Access Journals (Sweden)

    Eloisa Malbrán

    2017-08-01

    Full Text Available The benefits of the worldwide approval of new drugs for the treatment of acute C1-INH-HAE attacks may still not reach all patients. Identifying the current barriers in the access to medication, as well as conducting a detailed assessment of the progress in this area, is essential to achieve universal treatment. Two hundred and twenty five patients registered in the Argentina Hereditary Angioedema Patient Association (AHAEPA were randomly selected and invited to participate in a web based questionnaire on accessibility to icatibant and pdC1-INH, self-treatment, delay to treatment, and coverage. The data retrieved was compared to our previous reports in 2008 and 2013. We collected 156/225 answers. One hundred and eighteen (76% patients have either pdC1-INH (n = 86, icatibant (n = 10 or both (n = 22, while 38 (24% do not have access to treatment. In 2008, 26% had access while 82% had it in 2013. Thirty-two subjects (22% self-inject themselves, similar to 29% in 2013, even though between studies, widespread self-injection training activities have taken place. However, considering injections by proxy, home treatment reached 56%. Only half of the patients decide to receive treatment early during the attack. Ninety-nine patients (63% have full coverage, thirty (19% have no coverage at all and the rest only obtain partial reimbursement. Twenty-nine families (31% share a single treatment dose of the medication, better than 36% in 2013. Argentina's C1-INH-HAE patients had a sustained improvement in their access to medication. Efforts should continue to further improve accessibility and optimal management of HAE acute attacks to all patients in the country.

  12. Use of a C1 Inhibitor Concentrate in Adults ≥65 Years of Age with Hereditary Angioedema

    DEFF Research Database (Denmark)

    Bygum, Anette; Martinez-Saguer, Inmaculada; Bas, Murat

    2016-01-01

    BACKGROUND: Treatment of hereditary angioedema (HAE) in 'older adults' (those aged ≥65 years) has not been well studied. The international Berinert Patient Registry collected data on the use of intravenous plasma-derived, pasteurized, nanofiltered C1-inhibitor concentrate (pnfC1-INH; Berinert(®)/...

  13. Clinical similarities among bradykinin-mediated and mast cell-mediated subtypes of non-hereditary angioedema : a retrospective study

    NARCIS (Netherlands)

    Schulkes, Karlijn J G; van den Elzen, Mignon T.; Hack, Erik C.; Otten, Henderikus G; Bruijnzeel-Koomen, Carla A.F.M.; Knulst, André C.

    2015-01-01

    BACKGROUND: Non-hereditary angioedema (non-HAE) is characterized by local swelling due to self-limiting, subcutaneous or submucosal extravasation of fluid, and can be divided into three subtypes. These subtypes are believed to have different pathophysiological backgrounds and are referred to in

  14. Urticaria and Prodromal Symptoms Including Erythema Marginatum in Danish Patients with Hereditary Angioedema

    DEFF Research Database (Denmark)

    Rasmussen, Eva R; Valente de Freitas, Priscila; Bygum, Anette

    2016-01-01

    Erythema marginatum is a characteristic skin rash seen in patients with hereditary angioedema (HAE); however, it can be confused with urticaria, leading to delay in correct diagnosis. The aim of this study was to clarify how often erythema marginatum is misinterpreted as urticaria, potentially...... leading physicians to refrain from testing for HAE. Few studies have been published on urticaria and prodromal symptoms in HAE, thus the incidence of these parameters were also investigated. A total of 87 patients affiliated to the national HAE Centre were included. Retrospective and prospective data...... on skin eruptions and prodromal symptoms were collected. Fifty-six percent of 87 patients had a positive history of erythema marginatum. Half of the patients had experienced erythema marginatum being misinterpreted as urticaria. The most prevalent other prodromal symptoms were other skin symptoms, malaise...

  15. Hereditary angioedema: special consideration in children, women of childbearing age, and the elderly.

    Science.gov (United States)

    Kuhlen, James L; Banerji, Aleena

    2015-01-01

    This review on hereditary angioedema (HAE) focused on special topics regarding HAE in children, women of childbearing age, and the elderly. HAE is a rare autosomal dominant bradykinin-mediated disorder characterized by recurrent attacks of subcutaneous or submucosal swelling that usually affects the face, upper airway, extremities, gastrointestinal tract, or genitalia. These recurrent attacks cause significant morbidity and can be life threatening, especially when the swelling affects the airway. Our objective was to summarize the published data available on the disease epidemiology, pathophysiology, clinical presentation, on demand and prophylactic therapy, and focus on management considerations for these special patient populations. Unique aspects of HAE in women with regard to contraception, hormone replacement therapy, pregnancy, lactation, and menopause were also reviewed.

  16. A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes

    DEFF Research Database (Denmark)

    Joseph, Kusumam; Bains, Sonia; Tholanikunnel, Baby G

    2015-01-01

    BACKGROUND: Hereditary angioedema types I and II are caused by a functional deficiency of C1 inhibitor (C1-INH) leading to overproduction of bradykinin. The current functional diagnostic assays employ inhibition of activated C1s, however, an alternative, more physiologic method, is desirable...... dilutions of normal plasma were employed to validate the ability to detect known concentration of C1-INH in the plasma as a percent of normal. HAE types I and II were then tested. The level of functional C1-INH in all HAE types I and II plasma tested were less than 40% of our normal control...... samples were considered equivocal (4 controls and 38 patients). CONCLUSIONS: Diagnosis of HAE types I and II can be ascertained by inhibition of enzymes of the bradykinin-forming cascade; namely, factor XIIa and kallikrein. Either method yields functional C1-INH levels in HAE patients (types I & II...

  17. Canadian 2003 International Consensus Algorithm For the Diagnosis, Therapy, and Management of Hereditary Angioedema.

    Science.gov (United States)

    Bowen, Tom; Cicardi, Marco; Farkas, Henriette; Bork, Konrad; Kreuz, Wolfhart; Zingale, Lorenza; Varga, Lilian; Martinez-Saguer, Inmaculada; Aygören-Pürsün, Emel; Binkley, Karen; Zuraw, Bruce; Davis, Alvin; Hebert, Jacques; Ritchie, Bruce; Burnham, Jeanne; Castaldo, Anthony; Menendez, Alejandra; Nagy, Istvan; Harmat, George; Bucher, Christoph; Lacuesta, Gina; Issekutz, Andrew; Warrington, Richard; Yang, William; Dean, John; Kanani, Amin; Stark, Donald; McCusker, Christine; Wagner, Eric; Rivard, Georges-Etienne; Leith, Eric; Tsai, Ellie; MacSween, Michael; Lyanga, John; Serushago, Bazir; Leznoff, Art; Waserman, Susan; de Serres, Jean

    2004-09-01

    C1 inhibitor deficiency (hereditary angioedema [HAE]) is a rare disorder for which there is a lack of consensus concerning diagnosis, therapy, and management, particularly in Canada. European initiatives have driven the approach to managing HAE with 3 C1-INH Deficiency Workshops held every 2 years in Hungary starting in 1999, with the third Workshop having recently been held in May 2003. The European Contact Board has established a European HAE Registry that will hopefully advance our knowledge of this disorder. The Canadian Hereditary Angioedema Society/Société d'Angioédème Héréditaire du Canada organized a Canadian International Consensus Conference held in Toronto, Ontario, Canada, on October 24 to 26, 2003, to foster consensus between major European and North American HAE treatment centers. Papers were presented by investigators from Europe and North America, and this consensus algorithm approach was discussed. There is a paucity of double-blind placebo-controlled trials in the treatment of HAE, making levels of evidence to support the algorithm less than optimal. Enclosed is the consensus algorithm approach recommended for the diagnosis, therapy, and management of HAE and agreed to by the authors of this article. This document is only a consensus algorithm approach and requires validation. As such, participants agreed to make this a living 2003 algorithm (ie, a work in progress) and agreed to review its content at future international HAE meetings. The consensus, however, has strength in that it was arrived at by the meeting of patient-care providers along with patient group representatives and individual patients reviewing information available to date and reaching agreement on how to approach the diagnosis, therapy, and management of HAE circa 2003. Hopefully evidence to support approaches to the management of HAE will approach the level of meta-analysis of randomized controlled trials in the near future.

  18. Content validity of visual analog scales to assess symptom severity of acute angioedema attacks in adults with hereditary angioedema: an interview study.

    Science.gov (United States)

    McMillan, Carolyn Vivienne; Speight, Jane; Relan, Anurag; Bellizzi, Luca; Haase, Gerald; Cicardi, Marco

    2012-01-01

    Hereditary angioedema (HAE) is a rare, debilitating, potentially life-threatening condition characterized by recurrent acute attacks of edema of the skin, face/upper airway, and gastrointestinal and urogenital tracts. During a laryngeal attack, people with HAE may be at risk of suffocation, while other attacks are often associated with intense pain, disfigurement, disability, and/or vomiting. The intensity of some symptoms is known only to the person experiencing them. Thus, interview studies are needed to explore such experience and patient-reported outcome measures (PROMs) are required for systematic assessment of symptoms in the clinical setting and in clinical trials of treatments for acute HAE attacks. The aim of this interview study was to assess the content validity and suitability of four visual analog scale (VAS) instruments for use in clinical studies. The VAS instruments were designed to assess symptoms at abdominal, oro-facial-pharyngeal-laryngeal, peripheral, and urogenital attack locations. This is the first known study to report qualitative data about the patient's experience of the rare disorder, HAE. Semi-structured exploratory and cognitive debriefing interviews were conducted with 27 adults with a confirmed clinical/laboratory diagnosis of HAE (baseline plasma level of functional plasma protein C1 esterase inhibitor [C1INH] VAS-naïve. Experience of acute angioedema attacks was first explored, noting spontaneous mentions by participants of HAE symptomatology. Cognitive debriefing of the VAS instruments was undertaken to assess the suitability, comprehensibility, and relevance of the VAS items. Asymptomatic participants completed the VAS instruments relevant to their angioedema experience, reporting as if they were experiencing an acute angioedema attack at the time. Interviews were conducted in the clinic setting in the US and Italy over an 8-month period. Participants mentioned spontaneously almost all aspects of acute angioedema attacks covered

  19. Hereditary Angioedema

    DEFF Research Database (Denmark)

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

    2014-01-01

    of life. Most studies have been conducted in adults. We report a 13-year-old boy who quickly learned self-administration, which resulted in reduced frequency and severity of attacks. The aim of this report is to emphasize that children should be considered for self-administration training...

  20. Factor XII-independent activation of the bradykinin-forming cascade: Implications for the pathogenesis of hereditary angioedema types I and II.

    Science.gov (United States)

    Joseph, Kusumam; Tholanikunnel, Baby G; Bygum, Anette; Ghebrehiwet, Berhane; Kaplan, Allen P

    2013-08-01

    We have previously reported that prekallikrein expresses an active site when it is bound to high-molecular-weight kininogen (HK) and can digest HK to produce bradykinin. The reaction is stoichiometric and inhibited by C1 inhibitor (C1-INH) or corn trypsin inhibitor. Addition of heat shock protein 90 leads to conversion of prekallikrein to kallikrein in a zinc-dependent reaction. Our goal was to determine whether these reactions are demonstrable in plasma and distinguish them from activation through factor XII. Plasma was incubated in polystyrene plates and assayed for kallikrein formation. C1-INH was removed from factor XII-deficient plasma by means of immunoadsorption. We demonstrate that prekallikrein-HK will activate to kallikrein in phosphate-containing buffers and that the rate is further accelerated on addition of heat shock protein 90. Prolonged incubation of plasma deficient in both factor XII and C1-INH led to conversion of prekallikrein to kallikrein and cleavage of HK, as was seen in plasma from patients with hereditary angioedema but not plasma from healthy subjects. These results indicate that C1-INH stabilizes the prekallikrein-HK complex to prevent HK cleavage either by prekallikrein or by prekallikrein-HK autoactivation to generate kallikrein. In patients with hereditary angioedema, kallikrein and bradykinin formation can occur without invoking factor XII activation, although the kallikrein formed can rapidly activate factor XII if it is surface bound. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  1. Hereditary angioedema as a metabolic liver disorder: novel therapeutic options and prospects for cure

    Directory of Open Access Journals (Sweden)

    Rohan Ameratuga

    2016-11-01

    Full Text Available Hereditary angioedema (HAE is a rare autosomal dominant disorder caused by mutations of the SERPING1 or the Factor 12 genes. It is potentially fatal, particularly if not identified at an early stage. Apart from androgens, which are contraindicated in children and in pregnant women, a range of effective, albeit very expensive treatments have recently become available for HAE patients. The cost of these new treatments is beyond the reach of most developing countries. At this time, there is no cure for the disorder. In spite of mutations of the SERPING1 gene, autoimmunity and infections are not prominent features of the condition. Here we present the argument that HAE should be viewed primarily as a metabolic liver disorder. This conceptual paradigm shift will stimulate basic research and may facilitate new therapeutic approaches to HAE outlined in this paper. We suggest several novel potential treatment options for HAE from the perspectives of clinical immunology, molecular biology and liver transplantation. Many of these offer the prospect of curing the disorder. The effectiveness of these options are rapidly improving in many cases and their risks are decreasing. Given the very high costs of treating HAE, some of these curative options may become feasible in the next decade.

  2. Swedish children with hereditary angioedema report good overall health and quality of life despite symptoms.

    Science.gov (United States)

    Nygren, Anders; Nordenfelt, Patrik; Lindfors, Anders; Mallbris, Lotus; Björkander, Janne; Wahlgren, Carl-Fredrik

    2016-05-01

    Few studies have been published on children with hereditary angioedema (HAE), an autosomal dominant disease caused by mutations on chromosome 11. This study explored various aspects of the disease in the Swedish paediatric population. A retrospective questionnaire was sent to all 36 Swedish children known to have HAE, and a physician carried out follow-up telephone interviews. Most of the questionnaires were completed by the parents of 31 (86%) children with HAE, with or without their input, at a median age of nine years (range 1-17), and the physician also interviewed 29. HAE symptoms were experienced by 23 children, including abdominal attacks (96%), skin swelling (78%) and swelling in the mouth and/or upper airways (52%). Psychological stress was the most common trigger for abdominal attacks and trauma and sports triggered skin swelling. The majority (n = 19) had access to complement-1 esterase inhibitor concentrate at home. Current health and quality of life were generally rated as good, independent of whether the child had experienced HAE symptoms or not. Most children with HAE had experienced abdominal attacks and skin swelling, but their overall health and quality of life were generally perceived to be good. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  3. Factor XII mutations, estrogen-dependent inherited angioedema, and related conditions

    National Research Council Canada - National Science Library

    Binkley, Karen E

    2010-01-01

    The clinical, biochemical and genetic features of the conditions known as estrogen-dependent inherited angioedema, estrogen-associated angioedema, hereditary angioedema with normal C-1 inhibitor, type...

  4. Treatment of Hereditary Angioedema: items that need to be addressed in practice parameter

    Directory of Open Access Journals (Sweden)

    Dagen Callie

    2010-05-01

    Full Text Available Abstract Background Hereditary Angioedema (HAE is a rare, autosomal dominant (AD disorder caused by a C1 esterase inhibitor (C1-inh deficiency or qualitative defect. Treatment of HAE in many parts of the world fall short and certain items need to be addressed in future guidelines. Objective To identify those individuals who should be on long-term prophylaxis for HAE. Additionally, to determine if prodromal symptoms are sensitive and specific enough to start treatment with C-1 INH and possibly other newly approved therapies. Also, to discuss who is appropriate to self-administer medications at home and to discuss training of such patients. Methods A literature review (PubMed and Google was performed and articles published in peer-reviewed journals, which addressed HAE prophylaxis, current HAE treatments, prodromal symptoms of HAE and self-administration of injected home medications were selected, reviewed and summarized. Results Individuals whom have a significant decrease in QOL or have frequent or severe attacks and who fail or are intolerant to androgens should be considered for long-term prophylaxis with C1INH. Prodromal symptoms are sensitive, but non-specific, and precede acute HAE attacks in the majority of patients. Although the treatment of prodromal symptoms could lead to occasional overtreatment, it could be a viable option for those patients able to adequately predict their attacks. Finally, self-administration, has been shown to be feasible, safe and effective for patients who require IV therapy for multiple other diseases to include, but not limited to, hemophilia. Conclusions Prophylactic therapy, treatment at the time of prodromal symptoms and self-administration at home all should allow a reduction in morbidity and mortality associated with HAE.

  5. Hereditary angioedema: health-related quality of life in Canadian patients as measured by the SF-36.

    Science.gov (United States)

    Jindal, Nina Lakhani; Harniman, Elaine; Prior, Nieves; Perez-Fernandez, Elia; Caballero, Teresa; Betschel, Stephen

    2017-01-01

    Hereditary angioedema (HAE) is a rare but serious condition characterized by recurrent spontaneous attacks of angioedema affecting superficial tissues of upper respiratory and gastrointestinal tracts. The potentially fatal and disfiguring nature of HAE impacts the health-related quality of life (HRQoL) of patients with this condition. To assess the health-related quality of life of Canadian patients with HAE using the 36-item Short-Form Health Survey (SF-36v2). Twenty-one patients living in Canada over age 18 with known diagnosis of hereditary angioedema due to C1-INH deficiency (HAE), completed the SF-36v2 (generic HRQoL questionnaire). Results were compared to Canadian normative data by converting the SF-36 scores into z scores. The SF-36v2 showed a significant reduction in general health (p = 0.0063) in patients with HAE when compared with healthy Canadians. Percentage of patients with z scores below 0.8 (large effect) was 47.6% for general health subscale, 33.3% for bodily pain and vitality subscales and 28.6% for physical component scores. Mean scores of eight dimensions ranged from 57.7 to 88.9. Mean Physical and mental component scores were 49.1 and 50.4. Internal consistency of evaluation was demonstrated by Cronbach's alpha value above 0.7 for all scales. General perception of health was significantly different in these patients, compared to Canadian normative data. This study of Canadian patients with HAE shows that General Health is most frequently affected followed by Bodily Pain and Vitality, as measured by SF-36v2. The SF-36v2 offers valuable insight to assess quality of life in patients with HAE, however a larger number of Canadian patients and specific tools for assessment are needed for better evaluation.

  6. Helicobacter pylori infection as a triggering factor of attacks in patients with hereditary angioedema

    DEFF Research Database (Denmark)

    Visy, Beáta; Füst, George; Bygum, Anette

    2007-01-01

    BACKGROUND: Helicobacter pylori infection is considered among the causative factors of urticaria and angioedema. Having conducted a study on 65 patients, Hungarian authors reported in 2001 that successful eradication of H. pylori is followed by a significant reduction in the number of attacks in ...

  7. Angioedema hereditario: Historia familiar y manifestaciones clínicas en 58 pacientes Hereditary angioedema: Family history and clinical manifestations in 58 patients

    Directory of Open Access Journals (Sweden)

    Diego S. Fernández Romero

    2009-12-01

    Full Text Available El angioedema hereditario (AEH es una enfermedad rara, autosómica dominante, caracterizada por episodios de angioedema que comprometen la piel, el tracto gastrointestinal y la laringe. Analizamos las características epidemiológicas y clínicas en una serie de 58 pacientes, 53 (91% con diagnóstico de AEH tipo I y 5 (9% con tipo II. La edad media al inicio fue de 10.8 ± 9.5 años (0.1 a 59 y de 25.8 ± 16.2 años (2 a 77 en el momento del diagnóstico, con un retraso diagnóstico de 15.3 ± 14.3 años. El promedio de ataques en los 6 meses previos a la consulta fue de 7.4 ± 7.6 (0 a 40. Cincuenta y cuatro (93% presentaron ataques cutáneos, 50 (86% abdominales, 24 (41% laríngeos y 24 (41% cutáneos y abdominales combinados. Veintisiete (46.5% nunca utilizaron medicación preventiva para la enfermedad y 17 (29% recibieron danazol en diferentes dosis por diferentes periodos de tiempo. Durante los ataques, 15 (26% pacientes recibieron C1 inhibidor endovenoso alguna vez, 7 (12% recibieron plasma fresco y 40 (69% tratamiento sintomático. Ansiedad o situaciones de estrés y traumatismos fueron los desencadenantes más frecuentes. Identificamos a 6 (10% pacientes como primera mutación y a 52 (90% con historia familiar previa. Analizamos 20 troncos familiares identificando 205 individuos en riesgo de heredar la enfermedad, 109 (53% de ellos con síntomas o diagnóstico AEH. El total de individuos con síntomas de AEH fue de 145, de los cuales 19 (13% murieron por asfixia. Disminuir el retraso diagnóstico y ofrecer una terapéutica adecuada son desafíos a afrontar en el AEH.Hereditary angioedema (HAE is a rare autosomal dominant disease, characterized by episodes of edema typically involving the skin, gastrointestinal tract and larynx. We here describe the epidemiologic and clinical characteristic of a series of 58 patients with diagnosis of HAE, 53 (91% type I and 5 (9% type II. The mean age at first symptom was 10.8 ± 9.5 years and the mean

  8. Hereditary angioedema: beyond international consensus - circa December 2010 - The Canadian Society of Allergy and Clinical Immunology Dr. David McCourtie Lecture

    Directory of Open Access Journals (Sweden)

    Bowen Tom

    2011-02-01

    Full Text Available Abstract Background The 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema was published earlier this year in this Journal (Bowen et al. Allergy, Asthma & Clinical Immunology 2010, 6:24 - http://www.aacijournal.com/content/6/1/24. Since that publication, there have been multiple phase III clinical trials published on either prophylaxis or therapy of hereditary angioedema and some of these products have changed approval status in various countries. This manuscript was prepared to review and update the management of hereditary angioedema. Objective To review approaches for the diagnosis and management of hereditary angioedema (HAE circa December 2010 and present thoughts on moving from HAE management from international evidence-based consensus to facilitate more local health unit considerations balancing costs, efficacies of treatments, and risk benefits. Thoughts will reflect Canadian and international experiences. Methods PubMed searches including hereditary angioedema and diagnosis, therapy, management and consensus were reviewed as well as press releases from various pharmaceutical companies to early December 2010. Results The 2010 International Consensus Algorithms for the Diagnosis, Therapy and Management of Hereditary Angioedema is reviewed in light of the newly published phase III Clinical trials for prevention and therapy of HAE. Management approaches and models are discussed. Conclusions Consensus approach and double-blind placebo controlled trials are only interim guides to a complex disorder such as HAE and should be replaced as soon as possible with large phase IV clinical trials, meta analyses, data base registry validation of approaches including quality of life and cost benefit analyses, safety, and head-to-head clinical trials investigating superiority or non-inferiority comparisons of available approaches. Since not all therapeutic products are available in all jurisdictions

  9. Cost-utility analysis of Ruconest® (conestat alfa) compared to Berinert® P (human C1 esterase inhibitor) in the treatment of acute, life-threatening angioedema attacks in patients with hereditary angioedema

    Science.gov (United States)

    Holko, Przemysław; Paszulewicz, Anna

    2013-01-01

    Introduction Administration of human C1 esterase inhibitor (Berinert® P) from target import is the most widespread treatment strategy for patients with hereditary angioedema (HAE). However, a therapeutic health program including Ruconest® (conestat alfa) could shorten a patient's expectancy for a life-saving treatment. Aim To evaluate the cost-utility of Ruconest® (conestat alfa) financed from public funds within the newly introduced therapeutic health program compared with Berinert® P (human C1 esterase inhibitor) in the treatment of acute angioedema attacks in adults with HAE. Material and methods The cost-utility analysis from the Polish healthcare payer's perspective was performed for 1 year (2012). The costs and health outcomes were simulated for three pairs of eligible HAE patient groups (active treatment and corresponding placebo). The incremental costs of each intervention compared with placebo were listed together (direct or indirect comparisons between options were impossible due to limited clinical data available). Results The incremental cost-utility ratios (ICURs) for the evaluated interventions compared with placebo were as follows: EUR 15,226 per QALY (Ruconest®) and EUR 27,786 per QALY (Berinert® P). The probability of cost-utility (ICUR < EUR 24,279 per QALY) assessed for Ruconest® administered in the case of acute angioedema attack was 61% and 41% for Berinert® P. Conclusions The administration of Ruconest® in acute life-threatening angioedema attacks is economically justified from the Polish healthcare payer's perspective, results in lower costs and is characterized by higher cost-utility probability compared with Berinert® P. PMID:24278067

  10. Urticaria and angioedema.

    Science.gov (United States)

    Spickett, G

    2014-01-01

    Urticaria, also known as hives, and angioedema, where the swelling occurs below the skin instead of on the skin, are extremely common but there is a misconception that the most likely cause is an allergic reaction. Chronic urticaria in particular is rarely due to allergy. Equally for angioedema, many will consider the exceptionally rare hereditary angioedema (HAE), but in fact other medical causes are the most likely, in particular the use of angiotensin-converting enzyme inhibitor (ACE-I) drugs. Approximately 3-5% of patients receiving ACE-I will develop angioedema at some time in the course of their treatment.1 Stress is a major contributor to both chronic urticaria and recurrent angioedema. Treatment needs to focus on the use of long-acting, non-sedating, antihistamines. Corticosteroids may be used acutely but not long term.

  11. Icatibant, an inhibitor of bradykinin receptor 2, for hereditary angioedema attacks: prospective experimental single-cohort study

    Directory of Open Access Journals (Sweden)

    Regis Albuquerque Campos

    Full Text Available CONTEXT AND OBJECTIVE: Hereditary angioedema (HAE with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil.DESIGN AND SETTING: Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients.METHODS: Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored.RESULTS: 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age. The symptoms were: subcutaneous edema (22/24; abdominal pain (15/24 and upper airway obstruction (10/24. The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%; 10-20 (5/24; 20.8%; 20-30 (8/24; 33.4%; 30-60 (5/24; 20.8%; and 2 hours (1/24; 4.3%. The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6.CONCLUSION: HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients.

  12. Clinical Pattern and Acute and Long-term Management of Hereditary Angioedema Due to C1-Esterase Inhibitor Deficiency.

    Science.gov (United States)

    Gómez-Traseira, C; Pérez-Fernández, E; López-Serrano, M C; García-Ara, M C; Pedrosa, M; López-Trascasa, M; Caballero, T

    2015-01-01

    Hereditary angioedema due to C1-esterase inhibitor deficiency (HAE-C1-INH) is a life-threatening disease. To describe the clinical characteristics and management of patients with HAE-C1-INH during routine clinical practice. An observational, retrospective study was performed in patients with HAE-C1-INH. Demographic, clinical, and analytical data were collected from 2 periods: period A (October 2009-September 2010) and period B (October 2007-September 2009). We studied 112 patients with HAE-C1-INH (57.1% females). Age at onset of symptoms was 14.4 years (lower in patients who had experienced attacks in the previous year). In period B (n=87), 62.1% of patients presented at least 1 edema attack (median, 3.5 attacks/patient/2 years), and 19.1% of attacks were treated. In period A (n=77), 58.4% of patients were on maintenance therapy. Stanozolol was the most widely used drug (48.9%), with a mean weekly dose of 6.7 mg. At least 1 attack was recorded in 72.7% of patients (median, 3.0 attacks/patient/year), and 31.5% of the attacks were treated. Treatment of acute attacks increased by 12.4%. Age at onset of symptoms is associated with clinical expression of disease. The higher age at onset of symptoms, the fewer number of attacks per patient and year, and the lower dose of attenuated androgens necessary to control the disease than in other series lead us to hypothesize that HAE-C1-INH could have a less severe expression in Spain. Acute attacks seem to be treated increasingly often.

  13. Recurrent angioedema - a case report

    OpenAIRE

    Martins, Sandrina; Salgado, Miguel; Raposo, Filipa; Pinto, Diana; Martinho, Isabel; Araújo, Ana Rita

    2016-01-01

    Introduction: Hereditary angioedema (HA) is a rare cause of recurrent angioedema caused by a default in the gene that encodes the C1 esterase inhibitor (C1-INH). The oedema involves predominantly the face, limbs and genital and gastrointestinal tract. The involvement of the larynx, although less frequent, is the most severe clinical expression of HA and is potentially fatal. Case report: Clinical report of an eight-year-old female with multiple episodes of angioedema. The...

  14. Strong correlation of high EBNA-1-IgG levels with edematous attacks involving upper airway mucosa in hereditary angioedema due to C1-inhibitor deficiency.

    Science.gov (United States)

    Csuka, Dorottya; Varga, Lilian; Farkas, Henriette; Füst, George

    2012-01-01

    Elevated level of IgG-type antibodies against Type 1 nuclear antigen (anti-EBNA-1-IgG) of the Epstein-Barr virus is a strong risk factor for certain autoimmune diseases. We measured anti-EBNA-1 IgG titers in 107 patients with hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH). In the sera from 33 longitudinally tested patients, we found a very strong correlation (R>0.75, p=0.0005) between anti-EBNA-1-IgG titers measured in 2004 and 2010, respectively. High (>200 U/ml) anti-EBNA-1 levels were strongly correlated with the frequency of upper airway attacks (p=0.003) and the dose requirement of C1-inhibitor concentrate (p=0.008), while no significant association with the frequency of subcutaneous and abdominal attacks was found. These novel findings indicate that the underlying/triggering mechanisms of upper airway attacks in HAE-C1-INH may differ from that of other types of attacks and measurement of the anti-EBNA-1 IgG levels may be suitable for the prediction of upper airway attacks and C1-inhibitor concentrate requirement in HAE-C1-INH patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Angioedema Phenotypes: Disease Expression and Classification.

    Science.gov (United States)

    Wu, Maddalena Alessandra; Perego, Francesca; Zanichelli, Andrea; Cicardi, Marco

    2016-10-01

    Due to marked heterogeneity of clinical presentations, comprehensive knowledge of angioedema phenotypes is crucial for correct diagnosis and choosing the appropriate therapeutic approach. One of the ways to a meaningful clinical distinction can be made between forms of angioedema occurring "with or without wheals." Angioedema with wheals (rash) is a hallmark of urticaria, either acute or chronic, spontaneous or inducible. Angioedema without wheals may still be manifested in about 10 % of patients with urticaria, but it may also occur as a separate entity. Several classifications of angioedema as part of urticaria were published over time, while a latest one, released in 2014 (HAWK group consensus, see below), provided a classification of all forms of "angioedema without wheals" distinct from urticaria, which will be the focus of the present review. At this time, the HAWK consensus classification is the best in terms of covering the pathophysiology, mediators involved, angioedema triggers, and clinical expression. According to this classification, three types of hereditary angioedema (genetic C1-INH deficiency, normal C1-INH with factor XII mutations, and unknown origin) and four types of acquired angioedema (C1-INH deficiency, related to ACE inhibitors intake, idiopathic histaminergic, and idiopathic non-histaminergic) are presented. We will review the distinctive clinical features of each phenotype in details.

  16. Socioeconomic burden of hereditary angioedema

    DEFF Research Database (Denmark)

    Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen

    2014-01-01

    who were working or in school (n = 120), 72 provided work/school absenteeism data, resulting in an estimated 20 days missing from work/school on average per year; 51% (n = 84) indicated that HAE has hindered their career/educational advancement. CONCLUSION: HAE poses a considerable burden on patients...... and their families in terms of direct medical costs and indirect costs related to lost productivity. This burden is substantial at the time of attacks and in between attacks....

  17. Angioedema cervical

    OpenAIRE

    VALENZUELA V,CATALINA; GAC E,PATRICIO; CABANÉ T,PATRICIO

    2008-01-01

    Se presenta el caso de una mujer en la edad media de la vida, hipertensa en tratamiento, con el antecedente de cirugía bariátrica, que desarrolla cuadro de masa cervical asintomática en la que, luego de descartar otras patologías por imágenes y evolución, se diagnosticó Angioedema cervical, el que tuvo regresión total, prácticamente espontánea, en los días siguientes.

  18. International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency

    DEFF Research Database (Denmark)

    Caballero, Teresa; Farkas, Henriette; Bouillet, Laurence

    2012-01-01

    section. Regional anesthesia is preferred to endotracheal intubation. Breast cancer: Attenuated androgens should be avoided. Antiestrogens can worsen angioedema symptoms. In these cases anastrozole might be an alternative. Other issues addressed include special features of HAE-C1-INH treatment in female...... devices, and progestins can be used. Pregnancy: Attenuated androgens are contraindicated and should be discontinued before attempting conception. Plasma-derived human C1 inhibitor concentrate (pdhC1INH) is preferred for acute treatment, short-term prophylaxis, or long-term prophylaxis. Tranexamic acid...... labor and delivery might not be clinically indicated, but pdhC1INH therapeutic doses (20 U/kg) should be available. Nevertheless, each case should be treated based on HAE-C1-INH symptoms during pregnancy and previous labors. pdhC1INH prophylaxis is advised before forceps or vacuum extraction or cesarean...

  19. Angioedema due to Systemic Isotretinoin Therapy

    Directory of Open Access Journals (Sweden)

    Pelin Üstüner

    2014-01-01

    Full Text Available Angioedema is the swelling of the mucosal membranes as a variant of urticaria induced by hereditary C1 esterase inhibitor enzyme deficiency, certain foods, or drugs. Herein, we report the case of a 23-year-old woman, with mild-moderate acne presenting with widespread facial angioedema on the 2nd day of systemic isotretinoin treatment. The patient had taken no drugs other than isotretinoin in the preceding days and had no known food allergy. Her angioedema was resolved after the isotretinoin was discontinued. We want to draw the attention of dermatologists to this rare adverse allergic effect of isotretinoin which is frequently used in the treatment of acne vulgaris.

  20. Microflora and chemical composition of dental plaque from subjects with hereditary fructose intolerance.

    OpenAIRE

    Hoover, C I; Newbrun, E; Mettraux, G; Graf, H

    1980-01-01

    We compared the microbiological and chemical composition of dental plaque from subjects with hereditary fructose intolerance who restrict their dietary sugar intake with that of control subjects who do not. The two groups showed no significant differences in chemical composition of plaque: the mean protein, carbohydrate, calcium, magnesium, and phosphate contents were similar. Dental plaque from both groups contained similar numbers of total colony-forming units per microgram of plaque protei...

  1. Refractory Angioedema in a Patient with Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Zahra Habibagahi

    2015-07-01

    Full Text Available Angioedema secondary to C1 inhibitor deficiency has been rarely reported to be associated with systemic lupus erythematosus. A genetic defect of C1 inhibitor produces hereditary angioedema, which is usually presented with cutaneous painless edema, but edema of the genital area, gastrointestinal and laryngeal tracts have also been reported. In lupus patients, angioedema may be the result of an acquired type of C1 inhibitor deficiency, most probably due to antibody formation directed against the C1 inhibitor molecule. Herein we report a new case of lupus nephritis that developed angioedema and a rapid course of disease progression with acute renal failure and alveolar hemorrhage without response to high dose steroid and plasmapheresis.

  2. Hives and Angioedema

    Science.gov (United States)

    ... water, pressure on the skin, emotional stress and exercise. Underlying medical conditions. Hives and angioedema also occasionally occur in response to blood transfusions, immune system disorders such as lupus, some types of cancer such as lymphoma, certain ...

  3. Angiotensin Converting Enzyme-induced Angioedema - A Dangerous New Epidemic

    DEFF Research Database (Denmark)

    Rasmussen, Eva Rye; Mey, Kristianna; Bygum, Anette

    2013-01-01

    to asphyxia has increased. This is mainly due to pharmaceuticals such as angiotensin converting enzyme-inhibitors, which are extensively used worldwide. Some aspects of the pathophysiology have been elucidated and the vasoactive molecule bradykinin is shown to be one of the main causative agents....... The diagnosis is often delayed and traditional treatment usually ineffective. Complement C1 inhibitor concentrate and bradykinin receptor antagonists, normally used to treat patients with hereditary angioedema, have shown good results when used in patients with bradykinin-mediated angioedema. This review...

  4. Angioedema: 5 years' experience, with a review of the disorder's presentation and treatment.

    Science.gov (United States)

    Megerian, C A; Arnold, J E; Berger, M

    1992-03-01

    Angioedema is a problem that the otolaryngologist-head and neck surgeon is often asked to treat. This report concerns 17 patients admitted for care during a 5-year period. At their initial presentation, 94% of these patients manifested signs and symptoms of angioedema in the head and neck; three of them required urgent tracheotomy or intubation. As treatment of complement-mediated angioedema is distinct, an etiology-specific diagnostic and treatment protocol is presented. Of the patients, 35% had recent initiation of angiotensin-converting enzyme (ACE) inhibitor therapy for hypertension, and 6% demonstrated classic hereditary angioedema. However, the majority of them (59%) had unclear etiologies for their symptoms. Since angioedema is the final result of several possible abnormalities, a thorough knowledge of the differential diagnosis and clinical presentation is vital to patient management.

  5. Burden of Illness in Hereditary Angioedema

    DEFF Research Database (Denmark)

    Bygum, Anette; Aygören-Pürsün, Emel; Beusterien, Kathleen

    2015-01-01

    attacks, and passing HAE to children, reduced work/school productivity, and limited career/educational achievement. Patient caregivers also experienced worry and work/activity interruption during the attacks. In conclusion, a conceptual model was developed illustrating the hypothesized relationships among...... of HAE on health-related quality of life (HRQoL): (i) unnecessary treatments and procedures, (ii) symptom triggers, (iii) attack impacts, (iv) caregiver impacts, and (v) long-term impacts. Patients for example experienced unnecessary medical procedures due to diagnostic delays, anxiety and fear about...

  6. Burden of Illness in Hereditary Angioedema

    DEFF Research Database (Denmark)

    Bygum, Anette; Aygören-Pürsün, Emel; Beusterien, Kathleen

    2015-01-01

    of HAE on health-related quality of life (HRQoL): (i) unnecessary treatments and procedures, (ii) symptom triggers, (iii) attack impacts, (iv) caregiver impacts, and (v) long-term impacts. Patients for example experienced unnecessary medical procedures due to diagnostic delays, anxiety and fear about...... attacks, and passing HAE to children, reduced work/school productivity, and limited career/educational achievement. Patient caregivers also experienced worry and work/activity interruption during the attacks. In conclusion, a conceptual model was developed illustrating the hypothesized relationships among...

  7. The humanistic burden of hereditary angioedema

    DEFF Research Database (Denmark)

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

    2014-01-01

    % experienced an attack in more than one site. The impact of HAE on daily activities was high during attacks and did not vary significantly by body site affected; patients also reported that HAE impacted their daily activities between attacks. Patients reported substantial anxiety about future attacks......, traveling, and passing HAE to their children. Based on Hospital Anxiety and Depression Scale scores, 38 and 14% had clinically meaningful anxiety and depression, respectively. Despite standard of care, HAE patients still have frequent and painful attacks. Patients experience substantial impairment...

  8. Trifluoperazine-Induced Angioedema

    Directory of Open Access Journals (Sweden)

    Mugtaba Osman

    2014-01-01

    Full Text Available Angioedema is a serious adverse drug reaction that can rarely be associated with trifluoperazine treatment. We present the case of a 44-year-old male with an established diagnosis of schizoaffective disorder, for which trifluoperazine therapy was considered. He presented to the emergency department with bilateral lower limb oedematous painful erythematous swelling that eased off completely when trifluoperazine was stopped. The possibility of allergic reaction, such as angioedema, should always be kept in mind by psychiatrists and mental health professionals when prescribing trifluoperazine antipsychotic.

  9. Incidence of cardiac arrhythmias in asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

    Science.gov (United States)

    Shizukuda, Yukitaka; Tripodi, Dorothy J; Zalos, Gloria; Bolan, Charles D; Yau, Yu-Ying; Leitman, Susan F; Waclawiw, Myron A; Rosing, Douglas R

    2012-03-15

    It is not well known whether systemic iron overload per se in hereditary hemochromatosis (HH) is associated with cardiac arrhythmias before other signs and symptoms of cardiovascular disease occur. In the present study, we examined the incidence of cardiac arrhythmia in cardiac asymptomatic subjects with HH (New York Heart Association functional class I) and compared it to that in age- and gender-matched normal volunteers. The 42 subjects with HH and the 19 normal control subjects were recruited through the National Heart, Lung, and Blood Institute-sponsored "Heart Study of Hemochromatosis." They completed 48-hour Holter electrocardiography ambulatory monitoring at the baseline evaluation. The subjects with HH were classified as newly diagnosed (group A) and chronically treated (group B) subjects. All subjects with HH had C282Y homozygosity, and the normal volunteers lacked any HFE gene mutations known to cause HH. Although statistically insignificant, the incidence of ventricular and supraventricular ectopy tended to be greater in the combined HH groups than in the controls. Supraventricular ectopy was more frequently noted in group B compared to in the controls (ectopy rate per hour 11.1 ± 29.9 vs 1.5 ± 3.5, p cardiac arrhythmias was not significantly reduced after 6 months of intensive iron removal therapy in the group A subjects. No life-threatening arrhythmias were observed in our subjects with HH. In conclusion, our data suggest that the incidence of cardiac arrhythmias is, at most, marginally increased in asymptomatic subjects with HH. A larger clinical study is warranted to further clarify our observation. Published by Elsevier Inc.

  10. Glucose metabolism after normalization of markers of iron overload by venesection in subjects with hereditary hemochromatosis.

    Science.gov (United States)

    Hatunic, Mensud; Finucane, Francis M; Norris, Suzanne; Pacini, Giovanni; Nolan, John J

    2010-12-01

    Hereditary hemochromatosis (HH) is associated with abnormal glucose metabolism (AGM). We investigated the effect on glucose metabolism of normalization of the markers of iron overload by phlebotomy in subjects with HH. We prospectively studied 11 newly diagnosed subjects with HH and AGM using a standard 75-g oral glucose tolerance test. Basal quantitative insulin sensitivity check index (QUICKI) and stimulated oral glucose insulin sensitivity index (OGIS) insulin sensitivity was calculated from glucose and insulin data, whereas β-cell function was assessed using C-peptide concentration after adjusting for ambient insulin sensitivity. After normalization of ferritin and transferrin saturations by venesection for 12 (range, 8-16) months, subjects were studied again using the same methods. From 11 subjects with AGM at the time that HH was diagnosed, 7 had impaired glucose tolerance (IGT) and 4 had type 2 diabetes mellitus (T2DM). Normalization of the iron stores (ferritin and transferrin) improved the glucose tolerance status of 4 patients with IGT (to normal glucose tolerance), whereas 2 of those with IGT progressed to T2DM. In 5 patients, glucose tolerance status did not change (4 T2DM and 1 IGT). The area under the insulin and the C-peptide curve during the oral glucose tolerance test and the hepatic insulin extraction increased (P = .05), whereas no statistically significant changes occurred in insulin sensitivity. However, the disposition index, a measure of the ability of insulin release to compensate for insulin resistance, improved significantly (P = .02). Normalization of ferritin and transferrin saturation by venesection in subjects with HH and AGM led to improvements in some, but not all, measures of insulin secretion and action. Most patients with AGM had an improvement in glucose tolerance status, probably due to the augmented action of insulin in peripheral tissues. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Angioedema: Perioperative management.

    Science.gov (United States)

    Maynard, Andrew A; Burger, Christina F; Schlesinger, Joseph J

    2017-01-01

    To describe the perioperative management of a patient with acquired angioedema (AAE). A 66-year-old Caucasian male presented from an outside hospital with a history of acquired angioedema and gastrointestinal stromal tumor-related intractable urticaria and mastocytosis. He was admitted for urgent laparoscopic partial gastrectomy, secondary to gastric outlet obstruction symptomatology. Previous combined attacks were characterized by a widespread rash, abdominal pain and respiratory distress resulting in hospitalization. Following preoperative consultation with the patient's allergist and a hospital pharmacist, he was treated preoperatively with fresh frozen plasma and his home prednisone dose. C1-inhibitor (Berinert®) was on standby along with epinephrine, given that the underlying etiology (C1- inhibitor deficiency vs histaminergic) was not known. There were no intraoperative complications, and the patient was discharged home 3 days after the procedure. Optimization of perioperative outcomes in patients, especially during urgent or emergent surgery, with a history of angioedema requires the development of a patient-specific perioperative plan, including prophylaxis, rescue therapies and opioid-sparing strategies.

  12. Hereditary angioderma: an uncommon cause of acute abdomen. Abdominal computed tomography and ultrasound findings; Angioedema hereditario: una causa infrecuente de abdomen agudo. Hallazgos en la TC e ecografia abdominal

    Energy Technology Data Exchange (ETDEWEB)

    Cruz, R.A. de la; Oliver, J. M.; Bueno, A.; Albillos, J. C. [Fundacion Hospital Alcorcon. Madrid (Spain)

    2002-07-01

    We present an uncommon case of acute abdomen in a patient with hereditary angioderma. The ultrasound and CT findings described may suggest this diagnosis, thus avoiding useless surgical interventions in patients in whom the disease has not been previously diagnosed. (Author) 19 refs.

  13. Pathophysiology, clinical manifestation and management of angioedema - our experience

    Directory of Open Access Journals (Sweden)

    Aleksić Aleksandra

    2015-01-01

    Full Text Available Introduction. Angioedema is characterized by subcutaneous and/or submucosal swelling usually localized to the lips, eyelids, tongue, oral cavity, larynx and pharynx. Various types of angioedema, caused by different pathophysiologic mechanisms, can have the same or very similar clinical picture and require different diagnostic and therapeutic procedures. The immediate threat to life as a result of rapidly developed edema of the pharynx and larynx with airway obstruction requires endotracheal intubation or emergency tracheotomy. Standard therapy, which includes epinephrine, second-generation antihistamines and steroids, is not effective in the treatment of all types of angioedema. Objective. On the basis of the clinical presentation and course of angioedema, this retrospective study was aimed at contributing to a better understanding of the etiopathogenesis of the disease and at helping determine the most effective available treatment modalities. Methods. This retrospective study included patients treated under the diagnosis of angioedema of the upper aerodigestive tract between 2000 and 2012 in the Department of Otorhinolaryngology, Clinical Center of Banja Luka. Results. A total of 76 subjects were included in the study. The average age was 62.8 years. There were 40 (52.6% male and 36 (47.4% female patients. The largest number of patients (44.7% had type II angioedema. Almost half of the patients or 36 patients (47.4% were on treatment with an angiotensinconverting enzyme inhibitor (ACEi, but there was no statistically significant difference under the total number of patients (p=0.678. Conclusion. Better understanding of pathophysiologic mechanisms and the adoption of diagnostic protocols contributes to more effective treatment of angioedema.

  14. Recent Advances in Drug-Induced Angioedema

    Directory of Open Access Journals (Sweden)

    Naoko Inomata

    2012-01-01

    Full Text Available Angioedema is the end result of deep dermal, subcutaneous and/or mucosal swelling, and is potentially a life- threatening condition in cases where the pharynx or larynx is involved. Drug-induced angioedema has been reported to occur in response to a wide range of drugs and vaccines. Drug-induced angioedema, like other cutaneous drug reactions, has been reported to be most frequently elicited by beta-lactam antibiotics and nonsteroidal anti-inflammatory drugs, although reliable data from epidemiologic studies are scarce. Recent reports suggested an increasing role of angiotensin-converting enzyme inhibitors (ACEIs in the causation of life- threatening angioedema. ACEI-related angioedema is never accompanied by urticaria and occurs via a kinin- dependent mechanism. ACEI-related angioedema not only can start years after beginning the treatment, but it can then recur irregularly while under that treatment. Furthermore, allergy tests are unreliable for the diagnosis of ACEI-related angioedema, and so the relationship between angioedema and ACEIs is often missed and consequently quite underestimated. Accordingly, better understanding of the kinin-dependent mechanism, which is particular to angioedema, is necessary for the appropriate management of drug-induced angioedema.

  15. Hereditary Pancreatitis

    Science.gov (United States)

    ... E-News Sign-Up Home Hereditary Pancreatitis Hereditary Pancreatitis Hereditary Pancreatitis (HP) is a rare genetic condition characterized by ... of pancreatic attacks, which can progress to chronic pancreatitis . Symptoms include abdominal pain, nausea, and vomiting. Onset ...

  16. Cricotirotomía en paciente con angioedema de lengua secundario a inhibidor del enzima convertidor de la angiotensina

    OpenAIRE

    Acle Cervera, Leticia; Morales Angulo, Carmelo; García Zornoza, Roberto; Rubio Suárez, Antonio

    2013-01-01

    [ES] El angioedema hereditario por Inhibidores de la enzima convertidora de angiotensina (IECA) es un trastorno muy infrecuente. Suele afectar a la mucosa de la vía aérea supeior y producir cuadros obstructivos de rápida evolución con necesidad de tratamiento urgente. Se presenta el caso de un paciente en tratamiento con IECA y se revisa la prevalencia, fisiopatología y manejo de los angioedemas por tratamiento con IECA, así como los últimos tratamientos. [EN] Hereditary...

  17. Pharmacotherapy for Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Systematic Review.

    Science.gov (United States)

    Lawlor, Claire M; Ananth, Ashwin; Barton, Blair M; Flowers, Thomas C; McCoul, Edward D

    2017-11-01

    Objective Angioedema is a potentially life-threatening complication of angiotensin-converting enzyme inhibitor (ACEI) use, occurring in up to 0.5% of users. Although the pathophysiology of ACEI-induced angioedema is attributable to elevated serum bradykinin, standard management typically includes corticosteroids and antihistamines. We sought to summarize the evidence supporting pharmacotherapy for ACEI-induced angioedema. Data Sources PubMed, MEDLINE, and Embase portals. Methods A systematic literature review was conducted according to the PRISMA guidelines. Databases were queried by 3 independent reviewers for English-language studies published between 1980 and 2017. The initial search screened for all occurrences of "angioedema" and then was further refined to include studies of ACEI-related cases and exclude hereditary angioedema. Results Five articles representing 218 cases were identified, including 3 randomized controlled trials and 2 prospective case series with historical controls. One of 2 studies of icatibant (bradykinin B2 receptor antagonist) found more rapid symptom improvement than that with a control group of corticosteroids and antihistamines. Two studies of ecallantide (plasma kallikrein inhibitor) and 1 study of C1 inhibitor replacement found no significant benefit over control. No studies were identified that compared the efficacy of corticosteroids with antihistamines, of one dose with another, of fresh frozen plasma, or of combination therapy. Conclusion The efficacy of treatment of ACEI-induced angioedema with bradykinin antagonists, kallikrein inhibitor, and C1 inhibitor warrants further study. Although consistent benefit of these medications has not been demonstrated, their use has not caused harm. One study examining off-label use of icatibant has demonstrated efficacy over control. In addition, further study is needed to establish the efficacy and mechanism of action of standard pharmacotherapy such as corticosteroids and antihistamines in

  18. Clinical and Laboratory Characteristics That Differentiate Hereditary Angioedema in 72 Patients with Angioedema

    Directory of Open Access Journals (Sweden)

    Isao Ohsawa

    2014-01-01

    Conclusions: Early onset of AE, positive family history, recurrent AE in the extremities and GI tract, and suffocation are distinctive characteristics of HAE. A low serum level of C4 is a useful marker for making a differential diagnosis of HAE.

  19. Classification, diagnosis, and approach to treatment for angioedema

    DEFF Research Database (Denmark)

    Cicardi, M; Aberer, W; Banerji, A

    2014-01-01

    angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired...

  20. The Use of Plasma-Derived Complement C1-Esterase Inhibitor Concentrate (Berinert®) in the Treatment of Angiotensin Converting Enzyme-Inhibitor Related Angioedema

    DEFF Research Database (Denmark)

    Hermanrud, Thorbjørn; Duus, Nicolaj; Bygum, Anette

    2016-01-01

    concentrate is a well-established treatment option of hereditary and acquired complement C1-esterase inhibitor deficiency, which are also mediated by an increased level of bradykinin resulting in recurrent angioedema. We here present a case of severe angiotensin converting enzyme-inhibitor related angioedema...... (ACEi-AE) of the hypopharynx that completely resolved rapidly after the infusion of plasma-derived C1-inhibitor concentrate adding to the sparse reports in the existing literature.......Angioedema of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to pharmaceuticals influencing the generation or degradation of the vasoactive molecule bradykinin. Plasma-derived C1-esterase inhibitor...

  1. Hereditary Neuropathies

    Science.gov (United States)

    ... the appearance of an inverted champagne glass) or scoliosis (curvature of the spine). The symptoms of hereditary neuropathies may be apparent ... the appearance of an inverted champagne glass) or scoliosis (curvature of the spine). The symptoms of hereditary neuropathies may be apparent ...

  2. The Angiotensin-Converting-Enzyme-Induced Angioedema.

    Science.gov (United States)

    Bas, Murat

    2017-02-01

    The bradykinin B2 receptor antagonist icatibant is effective in angiotensin-converting enzyme inhibitor-induced angioedema. The drug is not approved officially for this indication and has to be administered in an emergency situation off-label. Corticosteroids or antihistamines do not seem to work in this condition. The effectiveness of C1-esterase-inhibitor in angiotensin-converting enzyme-induced angioedema must be verified in a double-blind study. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. The role of serial physical examinations in the management of angioedema involving the head and neck: A prospective observational study

    Directory of Open Access Journals (Sweden)

    Gary Linkov

    2016-03-01

    Full Text Available Objective: To elucidate the progression of angioedema of the head and neck with routine management and to assess the utility of serial physical exams and fiberoptic laryngoscopy in its management. Methods: This study was a prospective observational research. From 2013 to 2014, a prospective observational study was conducted at a tertiary referral center. Forty patient were approached, 7 refused, 33 (18–90 years old were enrolled. Patients presented with angioedema involving the head and neck over a 12 month period were asked to participate in the study. Physical examination and fiberoptic laryngoscopy were performed at presentation and then repeated at least 1 h later. Results: Thirty-three patients with head and neck angioedema from any cause were enrolled (mean age 58, range 23–89 years. The upper lip was the most commonly involved site (58%. On reevaluation, 82% of patients reported subjective improvement in symptoms. The association between subjective improvement and the physical exam, including fiberoptic laryngoscopy findings, was statistically significant (P < 0.001. Conclusion: In stable patients with angioedema of any head and neck subsite, self-reported symptoms are associated with clinical stability or improvement as assessed by physical signs and fiberoptic laryngoscopy. Patients' symptoms may be an appropriate surrogate to monitor clinical status without the need for routine serial physical examinations or fiberoptic laryngoscopy, though further study is needed. Keywords: Angioedema, Physical examination, Fiberoptic laryngoscopy

  4. How Not to Be Misled by Disorders Mimicking Angioedema

    DEFF Research Database (Denmark)

    Andersen, Michelle Fog; Longhurst, Hilary J; Rasmussen, Eva Rye

    2016-01-01

    with subcutaneous or submucosal swelling and falsely be assumed to be angioedema. The clinicians at the emergency department and in the immunology/allergy clinics must be skilled at recognizing the features of angioedema and its differential diagnosis. METHODS: The review is based on a literature search...

  5. Suspected tartrazine-induced acute urticaria/angioedema is only rarely reproducible by oral rechallenge.

    Science.gov (United States)

    Nettis, E; Colanardi, M C; Ferrannini, A; Tursi, A

    2003-12-01

    Tartrazine has been frequently linked to several diseases. However, a cause-and-effect role for tartrazine in these illnesses, especially in urticaria, has not always been established. The aim of this study is to determine the incidence of intolerance to tartrazine among subjects who experienced an acute episode of urticaria/angioedema following the ingestion of a meal or a product containing this substance. This was a retrospective study based on analysis of data of patients reported to have experienced episodes of urticaria and/or angioedema after ingesting meals or products containing tartrazine. At the first visit to the outpatients clinic, a careful anamnesis had been taken. Patients had then been submitted to the following diagnostic tests: IgE tests to common inhalant allergens and food allergens and a double-blind placebo-controlled challenge with tartrazine. A total of 102 subjects were enrolled in the study: 19 (18.6%) showed at least one relevant positive reaction to an IgE test for food allergy. Only one subject (1%) had reactions after ingestion of 5 mg of tartrazine, given on day 5. She did not have adverse reactions to placebo. This study shows that the percentage of acute urticaria and/or angioedema induced by tartrazine is very low (1%). In view of our results, we suggest that all physicians with patients who have suffered adverse reactions that could be attributed to tartrazine should also carefully evaluate other possible causes.

  6. 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.

  7. Drug-induced angioedema: experience of Italian emergency departments.

    Science.gov (United States)

    Bertazzoni, G; Spina, M T; Scarpellini, M G; Buccelletti, F; De Simone, M; Gregori, M; Valeriano, V; Pugliese, F R; Ruggieri, M P; Magnanti, M; Susi, B; Minetola, L; Zulli, L; D'Ambrogio, F

    2014-06-01

    Acute angioedema represents a cause of admission to the emergency department requiring rapid diagnosis and appropriate management to prevent airway obstruction. Several drugs, including angiotensin-converting enzyme inhibitors (ACE-I), nonsteroidal anti-inflammatory drugs (NSAIDs) and oral antidiabetics, have been reported to induce angioedema. The aim of this prospective observational study conducted in a setting of routine emergency care was to evaluate the incidence and extent of drug-induced non-histaminergic angioedema in this specific clinical setting, and to identify the class of drugs possibly associated with angioedema. Patients admitted to seven different emergency departments (EDs) in Rome with the diagnosis of angioedema and urticaria were enrolled during a 6-month period. Of the 120,000 patients admitted at the EDs, 447 (0.37 %) were coded as having angioedema and 655 (0.5 %) as having urticaria. After accurate clinical review, 62 cases were defined as drug-induced, non-histaminergic angioedema. NSAIDs were the most frequent drugs (taken by 22 out of 62 patients) associated with the angioedema attack. Of the remaining patients, 15 received antibiotic treatment and 10 antihypertensive treatment. In addition, we observed in our series some cases of angioedema associated with drugs (such as antiasthmatics, antidiarrheal and antiepileptics) of which there are few descriptions in the literature. The present data, which add much needed information to the existing limited literature on drug-induced angioedema in the clinical emergency department setting, will provide more appropriate diagnosis and management of this potentially life-threatening adverse event.

  8. [Quality control of DNA testing in hereditary diseases

    NARCIS (Netherlands)

    Ouweland, A.M.W. van den; Scheffer, H.

    2001-01-01

    The laboratories performing diagnostic studies regarding hereditary diseases and the specialists providing hereditary counselling are housed in clinical genetic centres. The laboratories are subject to the Special Medical Performances Act and have had licenses from the Ministry. The DNA diagnostic

  9. Anesthetic management of late pressure angioedema

    Directory of Open Access Journals (Sweden)

    Inês Furtado

    Full Text Available Abstract Background and objectives: Late pressure angioedema is a rare form of angioedema in which light pressure stimulus can lead to edema after 1-12 h. This uncommon and unreported entity is especially important in patients who undergo general anesthesia, for whom the usual harmless supine position, intravenous catheter insertion, standard monitoring, airway management and ventilation can lead to life threatening consequences as the trigger is a physical stimulus. Case report: In this report, we describe a successful perioperative anesthetic management of a 30 year old patient, proposed for intra-ocular lens insertion, with a severe form of the disease with peri-oral, tongue and limb edema presentation. Conclusion: Due to lack of quality evidence, our conduct was based on the pathophysiology mechanisms of the syndrome, histamine and pro-inflammatory cytokines release, with special focus on a careful peri-operative assessment and prophylaxis, minimization of all the possible pressure stimulus, especially in the airway structures, and a strict post-operative monitoring.

  10. Angioedema por rellenos faciales: Descripción de cinco casos Facial angioedema after filler injections: Description of five cases

    Directory of Open Access Journals (Sweden)

    Micaela A. Cosatti

    2010-12-01

    Full Text Available En los últimos años se ha incrementado la utilización de sustancias de relleno facial con fines estéticos. Estos productos, originalmente considerados inertes, se asocian con diversos efectos adversos localizados alrededor del sitio de la aplicación. Describimos a 5 mujeres con antecedentes de inyecciones de sustancia de relleno facial que presentaron como síntoma inicial angioedema facial duro y persistente seguido por la aparición de nódulos subcutáneos. Todas las pacientes fueron derivadas al servicio de alergia por sospecha de angioedema de causa alérgica sin respuesta al tratamiento con antihistamínicos. El angioedema inició 27.6 meses (1 a 48 luego de la inyección del producto, y las pacientes evolucionaron con brotes y remisiones que fueron tratados con corticoides orales y en 2 oportunidades con inyecciones locales. El tiempo medio desde el inicio de los síntomas hasta la remisión del angioedema fue 8.75 meses (1 a 24. A octubre de 2009 cuatro pacientes se mantuvieron en remisión persistente, luego de un seguimiento clínico de 24.5 meses (7 a 36. Una paciente continúa con exacerbaciones luego de 11 meses de iniciados los síntomas. Las sustancias de relleno facial pueden producir angioedema como evento adverso y deben ser consideradas en el diagnóstico diferencial del angioedema persistente. Sólo responden al tratamiento con esteroides y en algunos casos esteroides dependientes, con ciclosporina. La frecuencia de angioedema por rellenos faciales entre pacientes con angioedema asistidos en la Unidad de Asma, Alergia e Inmunología Clínica fue del 0.5%.The use of fillers for cosmetic purposes is becoming increasingly frequent. Although initially considered inert, these products produce adverse reactions around the injection site. We present 5 cases of women with a history of filler injections who presented a hard and persistent angioedema followed by local subcutaneous nodules . They were referred to the allergist for

  11. A case report of suspected angioedema in a child after ...

    African Journals Online (AJOL)

    infective and nonsteroidal anti-inflammatory drugs; also concomitant use of traditional medicines which is prevalent in some cultures. Cutaneous drug allergy is a common manifestation of adverse drug reactions. Keywords: Angioedema ...

  12. Delayed angioedema during therapy with angiotensin-converting enzyme inhibitors

    Directory of Open Access Journals (Sweden)

    Janković Slobodan M.

    2011-01-01

    Full Text Available Introduction. Angiotensin-converting enzyme inhibitors are leading cause of drug-induced angioedema, with incidence of 0.1 to 0.2%. The angioedema is not of immune nature; in predisposed individuals it is caused by accumulation of vasoactive mediators due to reduced activity of angiotensinconverting enzyme. Case report. We presented a 63-year old male patient suffering from hypertension and chronic obstructive pulmonary disease, who had developed two episodes of angioedema during a 5-year long therapy with enalapril. The first episode happened after three, and the second after five years of the therapy. On both occasions, the patient was admitted to the hospital and tracheotomy was avoided in the last moment. Conclusion. Long-term therapy with angiotensin-converting enzyme inhibitors could be associated with delayed angioedema, especially in patients with inflammation of airways caused by infection or chronic irritation.

  13. Hereditary hemochromatosis

    Directory of Open Access Journals (Sweden)

    Stephen A. Geller

    2015-03-01

    Full Text Available Hereditary hemochromatosis (HH is the most commonly identified autosomal recessive genetic disorder in the white population, characterized by increased intestinal iron absorption and secondary abnormal accumulation in parenchymal organs, not infrequently accompanied by functional impairment. This entity is associated with mutations of the HFE gene (located on the short arm of chromosome 6 at location 6p22.2; closely linked to the HLA-A3 locus, which encodes the HFE protein, a membrane protein thought to regulate iron absorption by affecting the interaction between transferrin receptor and transferrin.

  14. 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.

  15. Ticagrelor-Induced Angioedema: A Rare and Unexpected Phenomenon

    Directory of Open Access Journals (Sweden)

    Rajeev Seecheran

    2017-01-01

    Full Text Available Angioedema can cause potentially life-threatening airway obstruction. This case report describes an exceedingly rare episode of ticagrelor-induced hypersensitivity reaction, manifesting as angioedema with periorbital and likely respiratory involvement. The heart team should be vigilant for this precarious condition which may require emergent airway management. Desensitization protocols and alternative regimens (e.g., clopidogrel, prasugrel, and addition of an adjunctive anticoagulant should be considered when there is an absolute indication for antiplatelet therapy.

  16. Ticagrelor-Induced Angioedema: A Rare and Unexpected Phenomenon.

    Science.gov (United States)

    Seecheran, Rajeev; Seecheran, Valmiki; Persad, Sangeeta; Lalla, Sasha; Seecheran, Naveen Anand

    2017-01-01

    Angioedema can cause potentially life-threatening airway obstruction. This case report describes an exceedingly rare episode of ticagrelor-induced hypersensitivity reaction, manifesting as angioedema with periorbital and likely respiratory involvement. The heart team should be vigilant for this precarious condition which may require emergent airway management. Desensitization protocols and alternative regimens (e.g., clopidogrel, prasugrel, and addition of an adjunctive anticoagulant) should be considered when there is an absolute indication for antiplatelet therapy.

  17. Small Bowel Angioedema Secondary to Angiotensin-Converting Enzyme Inhibitors

    Science.gov (United States)

    Hurairah, Abu

    2016-01-01

    Small bowel angioedema induced by angiotensin-converting enzyme (ACE) inhibitors is a rare clinicopathologic entity. It frequently poses a diagnostic challenge and is often not recognized before surgical exploration. The present study illustrates that clinical awareness for this condition and adequate use of radiologic investigations can help make the correct diagnosis of ACE inhibitor-associated angioedema, thus avoiding the cost and morbidity associated with unnecessary interventions. PMID:28133581

  18. Small Bowel Angioedema Secondary to Angiotensin-Converting Enzyme Inhibitors

    OpenAIRE

    Inayat, Faisal; Hurairah, Abu

    2016-01-01

    Small bowel angioedema induced by angiotensin-converting enzyme (ACE) inhibitors is a rare clinicopathologic entity. It frequently poses a diagnostic challenge and is often not recognized before surgical exploration. The present study illustrates that clinical awareness for this condition and adequate use of radiologic investigations can help make the correct diagnosis of ACE inhibitor-associated angioedema, thus avoiding the cost and morbidity associated with unnecessary interventions.

  19. Is Pancreatic Cancer Hereditary?

    Science.gov (United States)

    ... Board Patient Education / Basics of Pancreatic Cancer Is pancreatic cancer hereditary? Cancer of the pancreas is a genetic ... found in cigarette smoke. The genetics of hereditary pancreatic cancer is a focus of research at Johns Hopkins. ...

  20. Antihypertensive drug associated angioedema: effect modification by race/ethnicity.

    Science.gov (United States)

    Reichman, Marsha E; Wernecke, Michael; Graham, David J; Liao, Jiemin; Yap, John; Chillarige, Yoganand; Southworth, Mary Ross; Keeton, Stephine; Goulding, Margie R; Mott, Katrina; Kelman, Jeffrey A

    2017-10-01

    Assess angioedema risk with exposure to angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) compared with beta-blockers, by race/ethnicity. New-user cohorts of Medicare beneficiaries 65 years or older initiating ACEI, ARB, or beta-blocker treatment from March 2007 to March 2014 were constructed. Angioedema incidence rates by drug and race/ethnicity were computed for 1-30 and 31-365 days of treatment. Cox proportional hazards regression was used to examine angioedema risk between cohorts. Angioedema incidence rates (per 1000 person years) in beta-blocker users were 1.80 (whites), 4.11 (blacks), 1.89 (Asians), and 2.10 (Hispanics); in ACEI users, 4.03, 23.77, 2.94, and 4.27; and in ARB users, 1.73, 3.11, 1.10, and 1.90, respectively. Incidence rates were significantly higher in the first 30 days of exposure for all drug × race/ethnic groups. Overall, angioedema risk increased among ACEI users (hazard ratio, 2.91; 95% confidence interval, 2.75-3.07) but not ARB users (0.93, 0.85-1.02) versus beta-blocker users. Angioedema risk with ACEIs versus beta-blockers increased more in blacks (6.28, 5.44-7.24) than whites (2.33, 2.19-2.48), Hispanics (2.04, 1.36-3.07), and Asians (1.48, 0.94-2.35). Compared with white beta-blocker users, angioedema risk was increased 2.9-fold in whites, 20.2-fold in blacks, and 2.3-fold in other race/ethnic groups combined during the first 30 days of ACEI exposure. There was significant effect modification of angioedema risk by race and ACEI use for blacks, but not for other race/ethnicity groups. Angioedema risk was significantly greater in the first 30 days of exposure for all, and highest among blacks. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Epidemiology of angioedema without wheals in an allergy and immunology center.

    Science.gov (United States)

    Malbrán, Eloisa; Fernández Romero, Diego; Juri, Maria Cecilia; Larrauri, Blas J; Malbrán, Alejandro

    2015-01-01

    We describe the diagnostic epidemiology, the clinical course, the family history and the response to treatment of patients with angioedema without wheals (AWW) at an Allergy and Immunology Clinical Center. We reviewed the case records of all patients at our office from January 1997 to April 2013. We recorded sex, age, age at onset of symptoms, family history of angioedema, number of visits to the office, type of angioedema, and response to treatment from those patients with angioedema without wheals. We classified angioedema according to its pathophysiology. We also describe those patients with angioedema mimics. From a total of 17,823 new patients, 303 had a presumptive diagnosis of angioedema without wheals. Twenty-three patients had an angioedema mimic. Forty percent were male and 60% were female. Average age at first visit was 40.6. Average number of visits was 2.4. Fifty-seven patients referred a family history. We attributed idiopathic angioedema to 55.7% of patients, 24.3% were drug related, 15.7% were due to C1 inhibitor deficiency, 2.1% were drug related+idiopathic angioedema, 1.4% were type III and 0.7% had exercise-induced angioedema. Ninety six percent of 53 evaluable idiopathic angioedema patients referred a benefit with anti-histamine therapy. AWW was a rare cause of consultation. Most of our patients had anti H1 responsive idiopathic angioedema and none had allergic angioedema. Women cases prevailed over men's. Family history and average age of onset of symptoms were different among the different types of angioedema.

  2. Isotretinoin induced rash, urticaria, and angioedema: a case report

    Directory of Open Access Journals (Sweden)

    Zonunsanga

    2015-10-01

    Full Text Available Isotretinoin is a vitamin A analogue, which is readily isomerized to tretinoin. It causes normalization of abnormal keratinisation. It also reduces sebum secretion. It also has anti-inflammatory as well as antibacterial properties. It has some adverse effects like teratogenecity, hypertriglyceridemia, pancreatitis, dryness of skin, cheilitis, altered liver functions etc. A 25 years old unmarried lady presented with acne vulgaris, who did not showed improvements with conventional (antibiotics therapy was given isotretinoin. She developed maculopapular rash, urticaria and angioedema Isotretinoin induced urticarial rashes and angioedema is rarely reported as far as our knowledge is concerned.

  3. How Not to Be Misled by Disorders Mimicking Angioedema

    DEFF Research Database (Denmark)

    Andersen, Michelle Fog; Longhurst, Hilary J; Rasmussen, Eva Rye

    2016-01-01

    BACKGROUND: Angioedema is a vascular reaction involving the lower dermis, subcutis and/or submucosal tissue and causing a temporary localized swelling in any part of the body. For many health care professionals, the diagnosis presents an ongoing challenge; several disorders may manifest with subc......BACKGROUND: Angioedema is a vascular reaction involving the lower dermis, subcutis and/or submucosal tissue and causing a temporary localized swelling in any part of the body. For many health care professionals, the diagnosis presents an ongoing challenge; several disorders may manifest...

  4. Urticaria and Angioedema – More than just Skin Deep!

    African Journals Online (AJOL)

    Family practitioners frequently encounter patients presenting with urticaria and angioedema. Patients attribute the symptoms to allergy, but the answer is not usually straightforward. The clinician needs to think like a detective and use a detailed history and clinical evaluation to inform the choice of investigations. The.

  5. Angiotensin converting enzyme induced angioedema: The need for ...

    African Journals Online (AJOL)

    Angiotensin converting enzyme induced angioedema: The need for patient education. ... The complication can be life threatening with serious morbidity and mortality if not promptly diagnosed from drug history and properly handled within the emergency unit. Apart from taking drug history concerning ACE inhibitor use in ...

  6. Fatal angioedema induced by angiotensin conversion enzyme (ACE ...

    African Journals Online (AJOL)

    2009-02-09

    Feb 9, 2009 ... ACE inhibitors are often prescribed in the treatment of hypertension, heart failure and kidney disease. These drugs are on the Essential Drugs List, and are therefore used at primary to tertiary health care levels in South Africa. Angioedema is considered a rare, but potentially fatal side-effect of this agent, ...

  7. Fatal angioedema induced by angiotensin conversion enzyme (ACE ...

    African Journals Online (AJOL)

    ACE inhibitors are often prescribed in the treatment of hypertension, heart failure and kidney disease. These drugs are on the Essential Drugs List, and are therefore used at primary to tertiary health care levels in South Africa. Angioedema is considered a rare, but potentially fatal side-effect of this agent, with a reported ...

  8. Alterations of coagulation and fibrinolysis in patients with angioedema due to C1-inhibitor deficiency

    Science.gov (United States)

    van Geffen, M; Cugno, M; Lap, P; Loof, A; Cicardi, M; van Heerde, W

    2012-01-01

    Patients with functional deficiency of C1-inhibitor (C1-INH) suffer from recurrent acute attacks (AA) of localized oedema associated with activation of the contact system, complement and fibrinolysis. To unravel further the role of coagulation and fibrinolysis in the pathophysiology of C1-INH deficiency, we performed simultaneous thrombin and plasmin generation measurements in plasma from patients with hereditary angioedema (HAE) due to C1-INH deficiency during AA (n = 23), in remission (R) (n = 20) and in controls (n = 20). During AA thrombin generation after in-vitro activation of plasma was higher than in controls, as demonstrated by shorter thrombin peak-time (P fibrinolysis inhibitor (TAFI) in patients during AA providing possible evidence for a regulatory effect on fibrinolysis. Plasminogen activator inhibitor-1 (PAI-1) was reduced in patients during AA indicating, together with the observed reduction of plasmin generation, the consumption of fibrinolytic factors. In conclusion, our results support the involvement of coagulation and fibrinolysis in the pathophysiology of HAE and show the possible application of simultaneous measurement of thrombin and plasmin generation to evaluate different clinical conditions in HAE patients. PMID:22288590

  9. [Hereditary ovarian cancer].

    Science.gov (United States)

    Zikán, M; Foretová, L; Cibula, D; Kotlas, J; Pohlreich, P

    2006-05-01

    This article reviews the topic of hereditary ovarian cancer, describes persons at risk of hereditary disposition to cancer and gives instructions for genetic counselling and molecular analysis, including contacts to specialized centres in the Czech Republic. Review. Institute of Biochemistry and Experimental Oncology, Charles University in Prague. Hereditary ovarian cancer occurs in three autosomal dominant syndromes: appropriate hereditary ovarian cancer (HOC), hereditary breast and ovarian cancer (HBOC) and hereditary non-poliposis colorectal cancer (HNPCC). Physician in practice or specialist at the clinic should focus interest on patients form families with frequent occurrence of breast and/or ovarian cancer, patients with early onset disease or tumour duplicity (breast and ovarian cancer). Hereditary disposition to ovarian (and breast) cancer could be assessed by molecular genetic analysis of two main susceptibility genes BRCA1 and BRCA2, or other genes in families with diverse tumours. Molecular genetic analysis should be in any cases indicated by experienced clinical genetic. In the Czech Republic, the consensus of genetic and clinical care of risk patients was published and specialized centres for families with hereditary predisposition were settled in Prague and Brno. Persons with hereditary susceptibility to cancer constitute noted group where painstaking dispensarisation and preventive care may prevent malignancy or detect it in the early stage.

  10. Disease Severity, Activity, Impact, and Control and How to Assess Them in Patients with Hereditary Angioedema

    DEFF Research Database (Denmark)

    Bygum, Anette; Busse, Paula; Caballero, Teresa

    2017-01-01

    within the same patient over time. During the past few years, several new on demand and prophylactic therapies have become available for HAE, allowing for individualized treatment. Therefore, to optimize HAE management, it is important to determine in all patients, the severity of their attacks...

  11. 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

    )/Reseau Canadien d'angioedeme hereditaire (RCAH) (www.haecanada.com) and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring) held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus...

  12. Health-related quality of life in Danish children with hereditary angioedema

    DEFF Research Database (Denmark)

    Aabom, Anne; Nguyen, Dan; Fisker, Niels

    2017-01-01

    have considerable impact on the health-related quality of life (HRQoL) in adult patients. Half the patients with C1-INH-HAE develop symptoms before the age of 10 years. However, the HRQoL in children with C1-INH-HAE is almost unexplored. Objective: To investigate HRQoL in Danish children with C1...... were the PedsQL (Child Self-Report and Parent Proxy-Report forms); the Children's Dermatology Life Quality Index; a nonvalidated, diseasespecific quality-of-life questionnaire; and two visual analog scales that rated general health. Results: The HRQoL scores in our study were comparable with the normal......-INH-HAE, including possible correlations to disease severity and attack frequency. Methods: All Danish children ages 2-18 years with C1-INH-HAE were invited to complete questionnaires regarding HRQoL; 14 (93%) agreed. Child self-report forms were used for children ages ≥5 years. The instruments used...

  13. Misdiagnosis trends in patients with hereditary angioedema from the real-world clinical setting

    DEFF Research Database (Denmark)

    Zanichelli, Andrea; Longhurst, Hilary J; Maurer, Marcus

    2016-01-01

    ) and appendicitis (50 of 185). A variety of other misdiagnoses were reported, including a substantial number of gastrointestinal disorders (excluding appendicitis). Misdiagnosis rates were similar between males (41.1%) and females (46.5%) and between C1-INH-HAE type I (43.7%) and type II (51.6%). Patients...... patients without (1.7 years; P appendicitis. Misdiagnosis results in marked delays in receiving the correct...

  14. Psychometric Field Study of Hereditary Angioedema Quality of Life Questionnaire for Adults

    DEFF Research Database (Denmark)

    Prior, Nieves; Remor, Eduardo; Pérez-Fernández, Elia

    2016-01-01

    , and Short Form 36-item Health Survey Version 2.0 (SF-36v2) were pilot tested internationally. Item reduction was based on both descriptive and exploratory factor analysis. Psychometric properties were assessed. RESULTS: Cross-cultural adaptation of the HAE-QoL was performed in 18 countries. The draft...... with and without psychiatric and/or psychological care (median: 74 vs 103; P ≤ .001). CONCLUSIONS: The HAE-QoL, currently available in 18 languages, showed good reliability and validity evidence....

  15. Clinical characteristics and real-life diagnostic approaches in all Danish children with hereditary angioedema

    DEFF Research Database (Denmark)

    Aabom, Anne; Andersen, Klaus E; Fagerberg, Christina

    2017-01-01

    approaches are limited. Our aim was to investigate the entire Danish cohort of children with HAE and non-HAE children of HAE patients for diagnostic approaches and clinical characteristics. RESULTS: We included 41 children: 22 with HAE and 19 non-HAE. Of the HAE children, 14 were symptomatic-median age...... concentrate. Unlike in other countries, androgens were not used in our pediatric cohort. Home therapy with C1 inhibitor concentrate was established in 9 cases: 6 children were trained in self-administration and 3 children were treated by parents. Of the children, 10 had been diagnosed by symptoms, including 3...

  16. Activation of the ficolin-lectin pathway during attacks of hereditary angioedema

    DEFF Research Database (Denmark)

    Csuka, Dorottya; Munthe-Fog, Lea; Hein, Estrid

    2014-01-01

    enrolled. We analyzed blood samples drawn during attacks, and obtained 35 samples from the same patients during symptom-free periods. The serum levels of ficolin-2, ficolin-3, MASP-2, ficolin-3/MASP-2 complex, C1-INH, and C4, as well as the extent of ficolin-3-mediated terminal complement complex (FCN3-TCC......) deposition, were measured using ELISA-based methods. RESULTS: Levels of MASP-2 and of the ficolin-3/MASP-2 complex were elevated (P TCC was lower (P TCC...

  17. HEREDITARY BREAST CANCER

    Directory of Open Access Journals (Sweden)

    E. M. Bit-Sava

    2013-01-01

    Full Text Available Hereditary breast cancer occurs in 5–20 % of cases and it is associated with inherited mutations in particular genes, such as BRCA1 и BRCA2 in most cases. The CHEK2, PTEN, TP53, ATM, RAD51, BLM, PALB2, Nbs genes are associated with low and median risks ofdeveloping breast cancer. Molecular genetic studies identify germinal mutations underlying hereditary breast cancer. In most cases hereditary breast cancer refers to triple-negative phenotype, which is the most aggressive type of breast cancer, that does not express the genes for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2. The review presents the diagnostic and treatment methods of hereditary breast cancer. Clinical-morphological aspects allow the new diagnostic and treatment methods of hereditary breast cancer to be identified. Poly (ADP-ribose polymerase (PARP inhibitors demonstrate the potential for effective treatment of BRCA-associated breast cancer.

  18. Attitude towards pre-implantation genetic diagnosis for hereditary cancer

    NARCIS (Netherlands)

    Lammens, Chantal; Bleiker, Eveline; Aaronson, Neil; Vriends, Annette; Ausems, Margreet; Jansweijer, Maaike; Wagner, Anja; Sijmons, Rolf; van den Ouweland, Ans; van der Luijt, Rob; Spruijt, Liesbeth; Garcia, Encarna Gomez; Ruijs, Marielle; Verhoef, Senno

    2009-01-01

    The use of pre-implantation genetic diagnosis (PGD) for hereditary cancer is subject to on-going debate, particularly among professionals. This study evaluates the attitude towards PGD and attitude-associated characteristics of those concerned: family members with a hereditary cancer predisposition.

  19. Angioedema hereditario: Guía de tratamiento

    OpenAIRE

    Alejandro Malbrán; Diego S. Fernández Romero; Alejandra Menéndez

    2012-01-01

    El angioedema hereditario (HAE) es una enfermedad rara, autosómica dominante, caracterizada por episodios que comprometen la piel, el tracto gastrointestinal y la laringe. Tiene una mortalidad histórica por asfixia del 15 al 50%. Es producida por la deficiencia funcional del C1 inhibidor. La identificación de la bradiquinina como mediador principal ha estimulado el desarrollo de nuevos medicamentos para tratar la enfermedad. El tratamiento del HAE se establece en consensos internacionales. El...

  20. [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. Copyright © 2012. Published by Elsevier Masson SAS.

  1. Diagnosis and Treatment of Urticaria and Angioedema: A Worldwide Perspective

    Science.gov (United States)

    2012-01-01

    Urticaria and angioedema are common clinical conditions representing a major concern for physicians and patients alike. The World Allergy Organization (WAO), recognizing the importance of these diseases, has contributed to previous guidelines for the diagnosis and management of urticaria. The Scientific and Clinical Issues Council of WAO proposed the development of this global Position Paper to further enhance the clinical management of these disorders through the participation of renowned experts from all WAO regions of the world. Sections on definition and classification, prevalence, etiology and pathogenesis, diagnosis, treatment, and prognosis are based on the best scientific evidence presently available. Additional sections devoted to urticaria and angioedema in children and pregnant women, quality of life and patient-reported outcomes, and physical urticarias have been incorporated into this document. It is expected that this article will supplement recent international guidelines with the contribution of an expert panel designated by the WAO, increasing awareness of the importance of urticaria and angioedema in medical practice and will become a useful source of information for optimum patient management worldwide. PMID:23282382

  2. Subjectivity

    Directory of Open Access Journals (Sweden)

    Jesús Vega Encabo

    2015-11-01

    Full Text Available In this paper, I claim that subjectivity is a way of being that is constituted through a set of practices in which the self is subject to the dangers of fictionalizing and plotting her life and self-image. I examine some ways of becoming subject through narratives and through theatrical performance before others. Through these practices, a real and active subjectivity is revealed, capable of self-knowledge and self-transformation. 

  3. Learning about Hereditary Hemochromatosis

    Science.gov (United States)

    Skip to main content Learning About Hereditary Hemochromatosis Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research ...

  4. Hereditary fructose intolerance

    Science.gov (United States)

    Fructosemia; Fructose intolerance; Fructose aldolase B-deficiency; Fructose-1, 6-bisphosphate aldolase deficiency ... substances build up in the liver. Hereditary fructose intolerance is inherited, which means it can be passed ...

  5. Assessment of 105 Patients with Angiotensin Converting Enzyme-Inhibitor Induced Angioedema

    DEFF Research Database (Denmark)

    Rasmussen, Eva Rye; von Buchwald, Christian; Wadelius, Mia

    2017-01-01

    Objective. To asses a cohort of 105 consecutive patients with angiotensin converting enzyme-inhibitor induced angioedema with regard to demographics, risk factors, family history of angioedema, hospitalization, airway management, outcome, and use of diagnostic codes used for the condition. Study ...

  6. Pharmacogenetics of ACE inhibitor-induced angioedema and cough: a systematic review and meta-analysis

    NARCIS (Netherlands)

    Mahmoudpour, Seyed Hamidreza; Leusink, Maarten; van der Putten, Lisa; Terreehorst, Ingrid; Asselbergs, Folkert W.; de Boer, Anthonius; Maitland-van der Zee, Anke H.

    2013-01-01

    Angioedema and cough are the two most important adverse effects of ACE inhibitors (ACEIs). Evidence exists that ACEI-related angioedema/cough is partly genetically determined and several genes have been identified to play a role in the development of ACEI-related adverse effects. This study was

  7. Dipeptidyl peptidase-4 inhibitor induced angioedema - an overlooked and potentially lethal adverse drug reaction?

    DEFF Research Database (Denmark)

    Scott, Susanne Irene; Andersen, Michelle Fog; Aagaard, Lise

    2018-01-01

    Introduction Angioedema is a potentially fatal adverse drug reaction of some medications, as swellings of the upper airways can cause death by asphyxiation. Angiotensin converting enzyme-inhibitors are widely known to cause angioedema but less is known about the association between dipeptidyl...

  8. [Hereditary kidney diseases in children].

    Science.gov (United States)

    Zhang, Yan-qin; Ding, Jie; Wang, Fang; Zhang, Hong-wen

    2013-04-18

    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.

  9. Hereditary cancer syndromes.

    Science.gov (United States)

    Rahner, Nils; Steinke, Verena

    2008-10-01

    Persons carrying mutations for hereditary cancer syndromes are at high risk for the development of tumors at an early age, as well as the synchronous or metachronous development of multiple tumors of the corresponding tumor spectrum. The genetic causes of many hereditary cancer syndromes have already been identified. About 5% of all cancers are part of a hereditary cancer syndrome. Selective literature review, including evidence-based guidelines and recommendations. Clinical criteria are currently available according to which many hereditary cancer syndromes can be diagnosed or suspected and which point the way to further molecular genetic analysis. A physician can easily determine whether these criteria are met by directed questioning about the patient's personal and family medical history. The identification of the causative germ line mutation in the family allows confirmation of the diagnosis in the affected individual and opens up the option of predictive testing in healthy relatives. Mutation carriers for hereditary cancer syndromes need long-term medical surveillance in a specialized center. It is important that these persons should be identified in the primary care setting and then referred for genetic counseling if molecular genetic testing is to be performed in a targeted, rational manner.

  10. Tongue abscess: a rare occurrence possibly mimicking angioedema

    Directory of Open Access Journals (Sweden)

    Alessandro Riccardi

    2013-10-01

    Full Text Available Despite the popularity of tongue piercing in recent years, the finding of a tongue abscess is considered extremely rare by international literature. The few available reports refer to a situation generally well documented objectively, posing problems of differential diagnosis for cancer, metastases, cysts, foreign bodies, intraparenchymal hemorrhage, macroglossia and edema of various origins. An acute enlargement of the tongue can be difficult to diagnose especially if there are no mucosal breaks or inflammation, and it may obstruct the upper airway and be a clinical challenge. Here we report a case observed in our emergency department which, at presentation, seemed suggestive for an angioedema.

  11. Hereditary gastric cancer.

    Science.gov (United States)

    Oliveira, Carla; Seruca, Raquel; Carneiro, Fátima

    2009-01-01

    Gastric cancer is a heterogeneous and highly prevalent disease, being the fourth most common cancer and the second leading cause of cancer associated death worldwide. Most cases are sporadic and familial clustering is observed in about 10% of the cases. Hereditary gastric cancer accounts for a very low percentage of cases (1-3%) and a single hereditary syndrome - Hereditary Diffuse Gastric Cancer (HDGC) - has been characterised. Among families that fulfil the clinical criteria for HDGC, about 40% carry CDH1 germline mutations, the genetic cause of the others being unknown. The management options for CDH1 asymptomatic germline carriers are intensive endoscopic surveillance and prophylactic gastrectomy. In this chapter we review the pathophysiology and clinicopathological features of HDGC and discuss issues related with genetic testing and management of family members.

  12. [Hereditary systemic autoinflammatory diseases].

    Science.gov (United States)

    Aróstegui, Juan I

    2011-01-01

    Systemic autoinflammatory diseases encompass different rare clinical entities characterized by recurrent acute inflammatory episodes secondary to a dysregulated inflammatory process. Since their first clinical descriptions, the Mendelian hereditary nature of some of them became evident, with their genetic and molecular basis being recently elucidated. There are disease-causing mutations in genes encoding for different proteins involved in the innate immune response and inflammation. Herein, we will introduce the reader to an updated review of the main clinical, physiopathological and therapeutic features of the different hereditary systemic autoinflammatory diseases. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  13. Angioedema: Classification, management and emerging therapies for the perioperative physician

    Directory of Open Access Journals (Sweden)

    Lopa Misra

    2016-01-01

    Full Text Available Angioedema is a rare condition which manifests as sudden localised, non-pitting swelling of certain body parts including skin and mucous membranes. It is vital that anaesthesiologists understand this condition, as it may present suddenly in the perioperative period with airway compromise. To identify literature for this review, the authors searched the PubMed, Medline, Embase, Scopus and Web of Science databases for English language articles covering a 10-year period, 2006 through 2016. Angioedema can be either mast-cell mediated or bradykinin-induced. Older therapies for histaminergic symptoms are well known to anaesthesiologists (e.g., adrenaline, anti-histamines and steroids, whereas older therapies for bradykinin-induced symptoms include plasma and attenuated androgens. New classes of drugs for bradykinin-induced symptoms are now available, including anti-bradykinin, plasma kallikrein inhibitor and C1 esterase inhibitors. These can be used prophylactically or as rescue medications. Anaesthesiologists are in a unique position to coordinate perioperative care for this complex group of patients.

  14. Angioedema hereditario: Tratamiento del ataque agudo en la Argentina

    Directory of Open Access Journals (Sweden)

    Alejandro Malbrán

    2014-06-01

    Full Text Available En el mundo, el angioedema hereditario (HAE afecta a 1 de cada 50 000 personas. Produce episodios de angioedema cutáneo, abdominal y laríngeos que generan gran incapacidad. La mortalidad por la enfermedad oscila entre 15 y 50%. Aunque en Argentina un concentrado plasmático de C1 inhibidor (pdC1INH ha estado aprobado y disponible por décadas para el tratamiento del ataque agudo, solo 15 (26% de 58 pacientes había recibido pdC1INH alguna vez hasta el año 2008, y solo 2(3.4% lo usaban regularmente. Luego de la aprobación de los nuevos medicamentos para HAE, incluido el icatibant en Argentina y de la publicación de las guías terapéuticas, 42 (82% de 51 pacientes del grupo original tienen pdC1INH para tratar el próximo ataque. Sin embargo, 16 (18% de estos pacientes continúan sin acceso a la medicación y otros 15 (35.7% acceden a través de otro enfermo en forma espuria. Solo 12 (28.6% de los pacientes con el medicamento puede auto tratarse en su domicilio. La mejora en el acceso a la medicación es importante pero debe extenderse a todos los afectados y facilitarse el auto-tratamiento.

  15. 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

  16. 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

  17. ACE-I Angioedema: Accurate Clinical Diagnosis May Prevent Epinephrine-Induced Harm

    Directory of Open Access Journals (Sweden)

    R. Mason Curtis

    2016-06-01

    Full Text Available Introduction: Upper airway angioedema is a life-threatening emergency department (ED presentation with increasing incidence. Angiotensin-converting enzyme inhibitor induced angioedema (AAE is a non-mast cell mediated etiology of angioedema. Accurate diagnosis by clinical examination can optimize patient management and reduce morbidity from inappropriate treatment with epinephrine. The aim of this study is to describe the incidence of angioedema subtypes and the management of AAE. We evaluate the appropriateness of treatments and highlight preventable iatrogenic morbidity. Methods: We conducted a retrospective chart review of consecutive angioedema patients presenting to two tertiary care EDs between July 2007 and March 2012. Results: Of 1,702 medical records screened, 527 were included. The cause of angioedema was identified in 48.8% (n=257 of cases. The most common identifiable etiology was AAE (33.1%, n=85, with a 60.0% male predominance. The most common AAE management strategies included diphenhydramine (63.5%, n=54, corticosteroids (50.6%, n=43 and ranitidine (31.8%, n=27. Epinephrine was administered in 21.2% (n=18 of AAE patients, five of whom received repeated doses. Four AAE patients required admission (4.7% and one required endotracheal intubation. Epinephrine induced morbidity in two patients, causing myocardial ischemia or dysrhythmia shortly after administration. Conclusion: AAE is the most common identifiable etiology of angioedema and can be accurately diagnosed by physical examination. It is easily confused with anaphylaxis and mismanaged with antihistamines, corticosteroids and epinephrine. There is little physiologic rationale for epinephrine use in AAE and much risk. Improved clinical differentiation of mast cell and non-mast cell mediated angioedema can optimize patient management.

  18. Angioedema por rellenos faciales: Descripción de cinco casos

    Directory of Open Access Journals (Sweden)

    Micaela A. Cosatti

    2010-12-01

    Full Text Available En los últimos años se ha incrementado la utilización de sustancias de relleno facial con fines estéticos. Estos productos, originalmente considerados inertes, se asocian con diversos efectos adversos localizados alrededor del sitio de la aplicación. Describimos a 5 mujeres con antecedentes de inyecciones de sustancia de relleno facial que presentaron como síntoma inicial angioedema facial duro y persistente seguido por la aparición de nódulos subcutáneos. Todas las pacientes fueron derivadas al servicio de alergia por sospecha de angioedema de causa alérgica sin respuesta al tratamiento con antihistamínicos. El angioedema inició 27.6 meses (1 a 48 luego de la inyección del producto, y las pacientes evolucionaron con brotes y remisiones que fueron tratados con corticoides orales y en 2 oportunidades con inyecciones locales. El tiempo medio desde el inicio de los síntomas hasta la remisión del angioedema fue 8.75 meses (1 a 24. A octubre de 2009 cuatro pacientes se mantuvieron en remisión persistente, luego de un seguimiento clínico de 24.5 meses (7 a 36. Una paciente continúa con exacerbaciones luego de 11 meses de iniciados los síntomas. Las sustancias de relleno facial pueden producir angioedema como evento adverso y deben ser consideradas en el diagnóstico diferencial del angioedema persistente. Sólo responden al tratamiento con esteroides y en algunos casos esteroides dependientes, con ciclosporina. La frecuencia de angioedema por rellenos faciales entre pacientes con angioedema asistidos en la Unidad de Asma, Alergia e Inmunología Clínica fue del 0.5%.

  19. Rituximab therapy in a patient with low grade B-cell lymphoproliferative disease and concomitant acquired angioedema

    Directory of Open Access Journals (Sweden)

    Kaur R

    2014-12-01

    Full Text Available Ravdeep Kaur, Aerik Anthony Williams, Catherine Baker Swift, Jason W Caldwell Wake Forest University School of Medicine, Wake Forest University, Winston-Salem, NC, USA Abstract: Acquired angioedema is often associated with significant morbidity. An underlying lymphatic malignancy, autoimmune disorder, adenocarcinoma, or other malignancy may be present. Screening for these disorders should occur in all patients with acquired angioedema as treatment may result in resolution of angioedema. Keywords: complement, C1-INH deficiency, ecallantide, hemopathy

  20. Hereditary Renal Diseases.

    Science.gov (United States)

    Mehta, Lakshmi; Jim, Belinda

    2017-07-01

    Hereditary kidney disease comprises approximately 10% of adults and nearly all children who require renal replacement therapy. Technologic advances have improved our ability to perform genetic diagnosis and enhanced our understanding of renal and syndromic diseases. In this article, we review the genetics of renal diseases, including common monogenic diseases such as polycystic kidney disease, Alport syndrome, and Fabry disease, as well as complex disorders such as congenital anomalies of the kidney and urinary tract. We provide the nephrologist with a general strategy to approach hereditary disorders, which includes a discussion of commonly used genetic tests, a guide to genetic counseling, and reproductive options such as prenatal diagnosis or pre-implantation genetic diagnosis for at-risk couples. Finally, we review pregnancy outcomes in certain renal diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. 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 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...

  2. BSACI guideline for the management of chronic urticaria and angioedema.

    Science.gov (United States)

    Powell, R J; Leech, S C; Till, S; Huber, P A J; Nasser, S M; Clark, A T

    2015-03-01

    This guidance for the management of patients with chronic urticaria and angioedema has been prepared by the Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is aimed at both adult physicians and paediatricians practising in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a Web-based system. Their comments and suggestions were carefully considered by the Standards of Care Committee. Where evidence was lacking, a consensus was reached by the experts on the committee. Included in this management guideline are clinical classification, aetiology, diagnosis, investigations, treatment guidance with special sections on children with urticaria and the use of antihistamines in women who are pregnant or breastfeeding. Finally, we have made recommendations for potential areas of future research. © 2015 John Wiley & Sons Ltd.

  3. [Cold-induced urticaria and angioedema. Classification, diagnosis and therapy].

    Science.gov (United States)

    Krause, K; Degener, F; Altrichter, S; Ardelean, E; Kalogeromitros, D; Magerl, M; Metz, M; Siebenhaar, F; Weller, K; Maurer, M

    2010-09-01

    The onset of wheals and/or angioedema following the exposure to cold may be associated with a number of different diseases. Most frequently this occurs in cold contact urticaria, a type of physical urticaria, which is characterized by a positive cold stimulation test. The clinical symptoms are based on cold-dependent mast cell activation with subsequent release of proinflammatory mediators. In cases of negative or atypical reaction to cold stimulation testing rare acquired atypical or familiar cold urticaria forms may be suspected. Strict avoidance of cold should be recommended as far as possible. As the underlying causes of cold contact urticaria are widely unknown, the symptomatic use of non-sedating antihistamines is the treatment of first choice. The very rare familiar cold auto-inflammatory syndrome (FCAS) is based on CIAS1/NLRP3 mutations and may be treated effectively by neutralization of pathogenic interleukin 1beta.

  4. 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.

  5. HFE-Associated Hereditary Haemochromatosis

    OpenAIRE

    Eijkelkamp, Emmeke J; Yapp, Thomas R; Powell, Lawrie W

    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 gene (HFE) in 1996 and two candidate mutations; the C282Y mutation has been shown to be responsible for the majority of the hereditary hemochromatosis cases worldwide. The gene discovery has led ...

  6. Genetics Home Reference: hereditary hyperekplexia

    Science.gov (United States)

    ... Neuromuscular Disorders Health Topic: Sudden Infant Death Syndrome Genetic and Rare Diseases Information Center (1 link) Hereditary hyperekplexia Additional NIH Resources (1 link) National Institute ...

  7. Genetics Home Reference: hereditary fructose intolerance

    Science.gov (United States)

    ... Home Health Conditions Hereditary fructose intolerance Hereditary fructose intolerance Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Hereditary fructose intolerance is a condition that affects a person's ability ...

  8. Genetics Home Reference: hereditary diffuse gastric cancer

    Science.gov (United States)

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

  9. Andrógenos en el tratamiento de mantenimiento a largo plazo del angioedema hereditario. ¿Es el momento de pensar en otras opciones?

    OpenAIRE

    Frías Iniesta, Jesús

    2016-01-01

    El angioedema hereditario (AEH) es una enfermedad transmitida con un patrón autosómico dominante, caracterizada por la presencia de angioedema recurrente y ocasionada por un defecto de la enzima conocida como inhibidor de C1. El principal mediador involucrado en el desarrollo del angioedema es la bradicinina

  10. Canine hereditary ataxia.

    Science.gov (United States)

    Urkasemsin, Ganokon; Olby, Natasha J

    2014-11-01

    The hereditary ataxias are a group of neurodegenerative diseases that cause a progressive (or episodic) cerebellar ataxia. A large number of different disorders have been described in different breeds of purebred dog, and in some instances, more than one disorder occurs in a single breed, creating a confusing clinical picture. The mutations associated with these disorders are being described at a rapid rate, potentially changing our ability to prevent, diagnose, and treat affected dogs. A breed-related neurodegenerative process should be suspected in any pure bred dog with slowly progressive, symmetric signs of ataxia. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. HFE-associated hereditary hemochromatosis

    NARCIS (Netherlands)

    Eijkelkamp, EJ; Yapp, TR; Powell, LW

    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

  12. EAMJ Oct Hereditary.indd

    African Journals Online (AJOL)

    HEREDITARY GINGIVAL FIBROMATOSIS: REPORT OF FAMILY CASE SERIES. E. G. WAGAIYU, R. N. NG'ANG'A and A. M. KEMOLI. SUMMARY. Hereditary gingival hyperplasia (HGF) is a rare condition characterised by hyperplastic, dense fibrous connective tissue with acanthotic gingival epithelium. A family presented.

  13. Fasciculations in human hereditary disease.

    Science.gov (United States)

    Finsterer, Josef; Aliyev, Rahim

    2015-06-01

    Fasciculations are a manifestation of peripheral nerve hyperexcitability in addition to myokymia, neuromyotonia, cramps, or tetany. Fasciculations occur in hereditary and non-hereditary diseases. Among the hereditary diseases, fasciculations are most frequently reported in familial amyotrophic lateral sclerosis (FALS), and spinal muscular atrophy (SMA). Among the non-hereditary diseases, fasciculations occur most frequently in peripheral nerve hyperexcitability syndromes (Isaac's syndrome, voltage-gated potassium channelopathy, cramp fasciculation syndrome, Morvan syndrome). If the cause of fasciculations remains unknown, they are called benign. Systematically reviewing the literature about fasciculations in hereditary disease shows that fasciculations can be a phenotypic feature in bulbospinal muscular atrophy (BSMA), GM2-gangliosidosis, triple-A syndrome, or hereditary neuropathy. Additionally, fasciculations have been reported in familial amyloidosis, spinocerebellar ataxias, Huntington's disease, Rett syndrome, central nervous system disease due to L1-cell adhesion molecule (L1CAM) mutations, Fabry's disease, or Gerstmann-Sträussler disease. Rarely, fasciculations may be a phenotypic feature in patients with mitochondrial disorders or other myopathies. Fasciculations are part of the phenotype in much more genetic disorders than commonly assumed. Fasciculations not only occur in motor neuron disease, but also in hereditary neuropathy, spinocerebellar ataxia, GM2-gangliosidosis, Huntington's disease, Rett syndrome, Fabry's disease, Gerstmann-Sträussler disease, mitochondrial disorders, or muscular dystrophies.

  14. Angioedema hereditario: Guía de tratamiento

    Directory of Open Access Journals (Sweden)

    Alejandro Malbrán

    2012-04-01

    Full Text Available El angioedema hereditario (HAE es una enfermedad rara, autosómica dominante, caracterizada por episodios que comprometen la piel, el tracto gastrointestinal y la laringe. Tiene una mortalidad histórica por asfixia del 15 al 50%. Es producida por la deficiencia funcional del C1 inhibidor. La identificación de la bradiquinina como mediador principal ha estimulado el desarrollo de nuevos medicamentos para tratar la enfermedad. El tratamiento del HAE se establece en consensos internacionales. El desarrollo de guías para el tratamiento de la enfermedad permite ordenar el uso de procedimientos diagnósticos y drogas. Describimos aquí algunas características farmacológicas de los medicamentos utilizados en el tratamiento del HAE en la Argentina: el concentrado plasmático de C1 inhibidor, el antagonista de la bradiquinina, icatibant, el andrógeno atenuado danazol y los agentes anti-fibrinolíticos ácidos épsilon aminocaproico (EACA y tranexámico. Asimismo, se describe su forma de uso y del control de los eventos adversos más frecuentes, así como las recomendaciones del último consenso internacional, aplicables para conformar una primera guía de tratamiento del HAE en la Argentina.

  15. Life Threatening Idiopathic Recurrent Angioedema Responding to Cannabis

    Directory of Open Access Journals (Sweden)

    Amit Frenkel

    2015-01-01

    Full Text Available We present a case of a 27-year-old man with recurrent episodes of angioedema since he was 19, who responded well to treatment with medical grade cannabis. Initially, he responded to steroids and antihistamines, but several attempts to withdraw treatment resulted in recurrence. In the last few months before prescribing cannabis, the frequency and severity of the attacks worsened and included several presyncope events, associated with scrotal and neck swelling. No predisposing factors were identified, and extensive workup was negative. The patient reported that he was periodically using cannabis socially and that during these periods he was free of attacks. Recent data suggest that cannabis derivatives are involved in the control of mast cell activation. Consequently, we decided to try a course of inhaled cannabis as modulators of immune cell functions. The use of inhaled cannabis resulted in a complete response, and he has been free of symptoms for 2 years. An attempt to withhold the inhaled cannabis led to a recurrent attack within a week, and resuming cannabis maintained the remission, suggesting a cause and effect relationship.

  16. Angioedema in a 47-year-old woman with hypocomplementemic urticarial vasculitis syndrome.

    Science.gov (United States)

    Jones, Julie M; Reich, Keith A; Raval, Deena G

    2012-02-01

    Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a type III hypersensitivity reaction characterized by urticaria with persistent acquired hypocomplementemia. Although HUVS is uncommon, it is important for physicians to be familiar with this disease, as the initial presentation is often life-threatening angioedema. The author reports the case of a 47-year-old white woman with a history of HUVS. She presented to an outpatient clinic complaining of a rash and difficulty swallowing. Urticaria and angioedema were diagnosed. The patient was given epinephrine in the clinic and then transferred to the hospital. Laboratory testing confirmed urticaria, and the patient was given intravenous methylprednisolone sodium succinate and an additional dose of epinephrine. After 1 week, the patient's angioedema improved.

  17. Hereditary pancreatitis for the endoscopist

    Science.gov (United States)

    Patel, Milan R.; Eppolito, Amanda L.

    2013-01-01

    Hereditary pancreatitis shares a majority of clinical and morphologic features with chronic alcoholic pancreatitis, but may present at an earlier age. The term hereditary pancreatitis has primarily been associated with mutations in the serine protease 1 gene (PRSS1) which encodes for cationic trypsinogen. PRSS1 mutations account for approximately 68–81% of hereditary pancreatitis. Mutations in other genes, primarily serine protease inhibitor Kazal type 1 (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) are also associated with hereditary pancreatitis. While chronic alcoholic pancreatitis may develop in the fourth or fifth decades, patients with hereditary pancreatitis may develop symptoms in the first or second decades of life. Hereditary pancreatitis is diagnosed either by detecting a causative gene mutation or by the presence of chronic pancreatitis in two first-degree or three second-degree relatives, in two or more generations, without precipitating factors and with a negative workup for known causes. Patients with hereditary pancreatitis may have recurrent acute pancreatitis and may develop pancreatic exocrine and endocrine insufficiency. Hereditary pancreatitis may involve premature trypsinogen activation or decreased control of trypsin. Recurrent inflammation can lead to acute pancreatitis and subsequently to chronic pancreatitis with parenchymal calcification. There is a markedly increased risk of pancreatic carcinoma compared with the general population. Patients are often referred for evaluation of pancreatitis, biliary or pancreatic ductal dilatation, jaundice, biliary obstruction, pancreatic duct stone or stricture, pancreatic pseudocysts, and for evaluation for malignancy. Medical treatment includes pancreatic enzyme supplementation, nutritional supplementation, diabetes management, and palliation of pain. Patients should avoid tobacco use and alcohol exposure. Hereditary pancreatitis is reviewed and recommendations for

  18. Angiodema due to oral acitretin and isotretinoin Angioedema por acitretina e isotretinoína oral

    Directory of Open Access Journals (Sweden)

    Roberto Rheingantz da Cunha Filho

    2011-08-01

    Full Text Available Angioedema may be caused by nonsteroidal antiinflammatory drugs, angiotensin- converting enzyme inhibitors, radiocontrast media, antibiotics, sea food etc. It can involve an allergic (IgE-mediated or non-allergic hypersensitivity reaction, both with a similar clinical presentation. While angioedema due to isotretionin has been described previously, this is the first description of angiodema due to acitretin. We report two uncommon cases of palpebral and labial angiodema due to retinoids, by acitretin and oral isotretinoin respectively: a 48-year-old man with psoriasis and a 24-year-old woman with severe acne resistant to antibiotics and topical drugs. In both cases the reaction persisted through-out treatment with these drugs, but resolved quickly after discontinuation. Reintroduction of the drugs brought on angioedema againAngioedema pode ser causado por diversos fármacos como : antiinflamatórios não-esteroidais, inibidores da ECA, contrastes, antibióticos e frutos do mar, entre outras causas. Pode ser uma reação alérgica, mediada por IgE, ou não-alérgica, com apresentações clínicas semelhantes. Angioedema por isotretinoína já foi relatado, mas não por acitretina. Relatamos dois casos, uma com angioedema palpebral e um labial, por acitretina e isotretinoína, respectivamente: um paciente de 48 anos com psoríase e uma paciente de 24 anos com acne resistente à terapia convencional. Em ambos casos a afecção persistiu durante o tratamento, resolveu com a interrupção e recidivou com reexposição

  19. [Hereditary and familial colorectal cancer].

    Science.gov (United States)

    Balaguer, Francesc

    2014-09-01

    Up to 5% of all colorectal cancer cases are caused by a known hereditary syndrome. These hereditary types often need a higher degree of clinical suspicion to be diagnosed and require specific and specialized management. In addition, diagnosing hereditary colorectal cancer has significant consequences not only for the patient, for whom there are effective preventative measures, but also for their families, who could be carriers of the condition. The most significant advances in the field of colorectal cancer have come from the diagnosis and characterization of these syndromes. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  20. 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.

  1. 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...

  2. Hereditary Fructose Intolerance

    Directory of Open Access Journals (Sweden)

    N.V. Nagornaya

    2014-06-01

    Full Text Available Hereditary fructose intolerance, the prevalence of which is 1 : 20,000 population, is diagnosed much less frequently than is found in child and adult populations. Presented pathology is caused by a deficiency in ferment aldolase B and block of fructose transformation in the gastrointestinal tract with the accumulation of unprocessed fructose in the intestine, manifesting by characteristic symptom and numerous biochemical changes in the body. The disease is asymptomatic until a person begins to use fructose, sucrose or sorbitol. This article describes the fructose metabolism, genetic aspects of the discussing disease, the diversity of its clinical manifestations. The authors presented modern diagnostic criteria and international approaches to diet therapy.

  3. Hereditary iron and copper deposition

    DEFF Research Database (Denmark)

    Aaseth, Jan; Flaten, Trond Peder; Andersen, Ole

    2007-01-01

    Hereditary deposition of iron (primary haemochromatosis) or copper (Wilson's disease) are autosomal recessive metabolic disease characterized by progressive liver pathology and subsequent involvement of various other organs. The prevalence of primary haemochromatosis is approximately 0.5%, about...

  4. Self-administration of intravenous C1-inhibitor therapy for hereditary angioedema and associated quality of life benefits

    DEFF Research Database (Denmark)

    Bygum, Anette; Andersen, Klaus Ejner; Mikkelsen, Carsten Sauer

    2009-01-01

    the impact of self-administered home therapy with intravenous C1-INH concentrate on QOL in patients with HAE. Nine patients experiencing frequent or severe debilitating HAE attacks were offered self-administration of C1-INH concentrate. QOL was assessed prior to and following home therapy using...... for the individual and combined components also improved significantly. No serious complications were documented during a follow-up period of 27 to 72 months. Self-administration of C1-INH improved QOL on both physical and psychological parameters. Patients were able to resume a normal life without restrictions...

  5. Elucidating the Mechanism of Gain of Toxic Function From Mutant C1 Inhibitor Proteins in Hereditary Angioedema

    Science.gov (United States)

    2017-10-01

    antibodies to 5 specifically blot wild-type C1INH in the pathologic polymers.. A FLAG tag was placed into the wild-type C1INH cDNA located immediately... constructs . The table below shows the results of this experiment. Origin of mutation Co-Transfection Construct A1AT Equiv. Replicate 1 Replicate 2... Construct n/a WT-C1INH n/a 1.00 1.01 A1AT E429K-Mu-C1INH Z 0.74 0.68 A1AT H421D-Mu-C1INH King’s 0.66 0.67 A1AT S148F-Mu-C1INH Silyama 0.71 0.54

  6. International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

    DEFF Research Database (Denmark)

    Farkas, H; Martinez-Saguer, I; Bork, K

    2017-01-01

    -HAE information card and medicine for emergency use. The regulatory approval status of the drugs for prophylaxis and for acute treatment is different in each country. Plasma-derived C1-INH, recombinant C1-INH, and ecallantide are the only agents licensed for the acute treatment of pediatric patients. Clinical...

  7. Risk of angioedema associated with levetiracetam compared with phenytoin: Findings of the observational health data sciences and informatics research network.

    Science.gov (United States)

    Duke, Jon D; Ryan, Patrick B; Suchard, Marc A; Hripcsak, George; Jin, Peng; Reich, Christian; Schwalm, Marie-Sophie; Khoma, Yuriy; Wu, Yonghui; Xu, Hua; Shah, Nigam H; Banda, Juan M; J Schuemie, Martijn

    2017-08-01

    Recent adverse event reports have raised the question of increased angioedema risk associated with exposure to levetiracetam. To help address this question, the Observational Health Data Sciences and Informatics research network conducted a retrospective observational new-user cohort study of seizure patients exposed to levetiracetam (n = 276,665) across 10 databases. With phenytoin users (n = 74,682) as a comparator group, propensity score-matching was conducted and hazard ratios computed for angioedema events by per-protocol and intent-to-treat analyses. Angioedema events were rare in both the levetiracetam and phenytoin groups (54 vs. 71 in per-protocol and 248 vs. 435 in intent-to-treat). No significant increase in angioedema risk with levetiracetam was seen in any individual database (hazard ratios ranging from 0.43 to 1.31). Meta-analysis showed a summary hazard ratio of 0.72 (95% confidence interval [CI] 0.39-1.31) and 0.64 (95% CI 0.52-0.79) for the per-protocol and intent-to-treat analyses, respectively. The results suggest that levetiracetam has the same or lower risk for angioedema than phenytoin, which does not currently carry a labeled warning for angioedema. Further studies are warranted to evaluate angioedema risk across all antiepileptic drugs. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  8. Hereditary xanthinuria. Evidence for enhanced hypoxanthine salvage.

    OpenAIRE

    Mateos, F A; Puig, J G; Jiménez, M L; Fox, I H

    1987-01-01

    We tested the hypothesis that there is an enhanced rate of hypoxanthine salvage in two siblings with hereditary xanthinuria. We radiolabeled the adenine nucleotide pool with [8-14C]adenine and examined purine nucleotide degradation after intravenous fructose. The cumulative excretion of radioactivity during a 5-d period was 9.7% and 9.1% of infused radioactivity in the enzyme-deficient patients and 6.0 +/- 0.7% (mean +/- SE) in four normal subjects. Fructose infusion increased urinary radioac...

  9. Abordagem anestésica de doente com angioedema hereditário proposto para cirurgia electiva

    OpenAIRE

    Conceição, Luís; Martinho, Hélder; Azenha, Marta

    2014-01-01

    O angioedema hereditário é uma entidade rara, com transmissão autossómica dominante, causada por deficiência no inibidor de C1. Esta condiciona uma ativação descontrolada da via clássica do complemento e da cascata das cininas, sendo responsável por episódios de angioedema com possível comprometimento da via aérea. Os autores descrevem um caso clínico de um doente com 36 anos com angioedema hereditário tipo I proposto para colecistectomia electiva sob anestesia geral, tendo sido tomadas algum...

  10. Hereditary Renal Cancer Syndromes

    Science.gov (United States)

    Haas, Naomi B.

    2013-01-01

    Inherited susceptibility to kidney cancer is a fascinating and complex topic. Our knowledge about types of genetic syndromes associated with an increased risk of disease is continually expanding. Currently, there are 10 syndromes associated with an increased risk of all types of renal cancer, which are reviewed herein. Clear cell renal cancer is associated with von Hippel Lindau disease, chromosome 3 translocations, PTEN hamartomatous syndrome and mutations in BAP1, as well as several of the genes encoding the proteins comprising the succinate dehydrogenase complex (SDHB/C/D). Type 1 papillary renal cancers arise in conjunction with germline mutations in MET and type 2 as part of Hereditary Leiomyomatosis and Renal Cell Cancer (FH mutations). Chromophone and oncocytic renal cancers are predominantly associated with Birt Hogg Dubé syndrome. Angiomyolipomas are commonly and their malignant counterpart epitheliod angiomyolipomas rarely are found in patients with Tuberous Sclerosis Complex. The targeted therapeutic options for the renal cancer associated with these diseases are just starting to expand, and are an area of active clinical research. PMID:24359990

  11. Hereditary xanthinuria. Evidence for enhanced hypoxanthine salvage.

    Science.gov (United States)

    Mateos, F A; Puig, J G; Jiménez, M L; Fox, I H

    1987-03-01

    We tested the hypothesis that there is an enhanced rate of hypoxanthine salvage in two siblings with hereditary xanthinuria. We radiolabeled the adenine nucleotide pool with [8-14C]adenine and examined purine nucleotide degradation after intravenous fructose. The cumulative excretion of radioactivity during a 5-d period was 9.7% and 9.1% of infused radioactivity in the enzyme-deficient patients and 6.0 +/- 0.7% (mean +/- SE) in four normal subjects. Fructose infusion increased urinary radioactivity to 7.96 and 9.16 X 10(6) cpm/g creatinine in both patients and to 4.73 +/- 0.69 X 10(6) cpm/g creatinine in controls. The infusion of fructose increased total urinary purine excretion to a mean of 487% from low-normal baseline values in the patients and to 398 +/- 86% in control subjects. In the enzyme-deficient patients, the infusion of fructose elicited an increase of plasma guanosine from undetectable values to 0.7 and 0.9 microM. With adjustments made for intestinal purine loss, these data support the hypothesis that there is enhanced hypoxanthine salvage in hereditary xanthinuria. Degradation of guanine nucleotides to xanthine bypasses the hypoxanthine salvage pathway and may explain the predominance of this urinary purine compound in xanthinuria.

  12. [Ataxias and hereditary spastic paraplegias].

    Science.gov (United States)

    Schüle, R; Schöls, L

    2017-07-01

    Hereditary ataxias and spastic paraplegias are genetic disorders with age-dependent nearly complete penetrance. The mostly monogenetic etiology allows one to establish the diagnosis, study pathogenesis and to develop new causative therapeutic approaches for these diseases. Both the causative genes as well as the clinical presentation overlap considerably between hereditary ataxias and spastic paraplegias. This strongly argues towards a united classification for these two groups of diseases. Next generation sequencing technologies have greatly expanded the number of genes known to be causative for hereditary ataxias and spastic paraplegias and allow simultaneous time- and cost-effective diagnostic testing of > 200 genes. However, repeat expansions and large genomic deletions must be considered separately. Here, we suggest a pragmatic algorithm for genetic testing in hereditary ataxias and spastic paraplegias that we have developed in our specialized outpatient clinics. Detailed phenotyping remains crucial to interpret the multitude of genetic variants discovered by high throughput sequencing techniques. Despite recent technical advances, a substantial proportion of ataxia and spastic paraplegia families are still without a molecular diagnosis. Beside new and so far undetected ataxia and spasticity genes, unusual mutation types including noncoding variants and polygenic inheritance patterns may contribute. Because of these clinical, genetic, and technological challenges, patients with hereditary ataxias and spastic paraplegias should be referred to specialized centers offering research and clinical studies. This will also help to recruit representative patient cohorts for upcoming interventional trials.

  13. 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

  14. Pathology of hereditary breast cancer

    OpenAIRE

    van der Groep, Petra; van der Wall, Elsken; van Diest, Paul J.

    2011-01-01

    Background Hereditary breast cancer runs in families where several members in different generations are affected. Most of these breast cancers are caused by mutations in the high penetrance genes BRCA1 and BRCA2 accounting for about 5% of all breast cancers. Other genes that include CHEK2, PTEN, TP53, ATM, STK11/LKB1, CDH1, NBS1, RAD50, BRIP1 and PALB2 have been described to be high or moderate penetrance breast cancer susceptibility genes, all contributing to the hereditary breast cancer spe...

  15. Consensus statement on the diagnosis, management, and treatment of angioedema mediated by Bradykinin. Part. II: treatment, follow-up, and special situations

    OpenAIRE

    Caballero, T.; Baeza, M. L.; Cabañas, R.; Campos, A.; Cimbollek, S.; Gómez-Traseira, C.; González-Quevedo, T.; Guilarte, M.; Jurado-Palomo, J.; Larco, J. I.; López-Serrano, M. C.; López-Trascasa, M.; Marcos, C.; Muñoz- Caro, J. M.; Pedrosa, M.

    2011-01-01

    Background: There are no previous Spanish guidelines or consensus statements on bradykinin-induced angioedema. Aim: To draft a consensus statement on the management and treatment of angioedema mediated by bradykinin in light of currently available scientifi c evidence and the experience of experts. This statement will serve as a guideline to health professionals. Methods: The consensus was led by the Spanish Study Group on Bradykinin-Induced Angioedema, a working group of the Spanish...

  16. Immunophenotyping of hereditary breast cancer

    NARCIS (Netherlands)

    van der Groep, P.|info:eu-repo/dai/nl/304810789

    2009-01-01

    Hereditary breast cancer runs in families where several family members in different generations are affected. Most of these breast cancers are caused by mutations in the high penetrance genes BRCA1 and BRCA2 which account for about 5% of all breast cancers. However, mutations in BRCA1 and BRCA2 may

  17. 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.

  18. Genetics Home Reference: hereditary hemochromatosis

    Science.gov (United States)

    ... several genes, including HAMP , HFE , HFE2 , SLC40A1 , and TFR2 , can cause hereditary hemochromatosis . Type 1 hemochromatosis results ... the HFE2 or HAMP gene. Mutations in the TFR2 gene cause type 3 hemochromatosis, and mutations in ...

  19. ACE Inhibitor-Induced Angioedema of the Intestine: Case Report, Incidence, Pathophysiology, Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    Gavin Oudit

    2001-01-01

    Full Text Available A case report of fosinopril-induced angioedema of the intestine with a chronic course accompanied by multiple acute exacerbations is described. Angiotensin-converting enzyme (ACE inhibitor-induced angioedema of the intestine (AIAI occurs in a minority of patients taking an ACE inhibitor. The clinical presentation encompasses acute abdominal symptoms, pronounced bowel edema and ascites with occasional facial and/or oropharyngeal swelling. AIAI is diagnosed based on the temporal relationship between the symptomatic presentation and drug use, absence of alternative diagnoses including other causes of angioedema, and the prompt resolution of symptoms upon discontinuation of the ACE inhibitor. Prompt radiological investigation (abdominal computerized tomography and/or ultrasound is critical in making an early diagnosis and in preventing unnecessary surgical intervention. There is a female predominance of AIAI, which may reflect the interaction of estradiol with the various pathways involved in the pathophysiology of AIAI. Management of AIAI consists mainly of conservative measures and discontinuation of the ACE inhibitor. Angiotensin II receptor antagonists should not be considered as appropriate alternatives. Awareness and knowledge of AIAI are important because of the increasing use of ACE inhibitors, current delays in making the diagnosis, obvious management strategies once the diagnosis is made and the dysutility of alternative diagnoses, which may lead to considerable morbidity. AIAI must be considered in patients taking ACE inhibitors who develop gastrointestinal complaints irrespective of the duration of the therapy.

  20. Genetic Variants of Thymic Stromal Lymphopoietin in Nonsteroidal Anti-Inflammatory Drug-Induced Urticaria/Angioedema.

    Science.gov (United States)

    Plaza-Serón, María Del Carmen; Blanca-López, Natalia; Pérez-Sánchez, Natalia; Doña, Inmaculada; Acosta-Herrera, Marialbert; Pino-Yanes, María; Flores, Carlos; Cornejo-García, José Antonio; Perkins, James R; Molina, Ana; Torres, Maria José; Blanca, Miguel; Canto, María Gabriela; Ayuso, Pedro

    2016-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequent agents involved in hypersensitivity drug reactions, with NSAID-induced urticaria and/or angioedema (NIUA) being the most common entity. Mast cells are key players in NIUA and are activated by thymic stromal lymphopoietin (TSLP). This cytokine functions through recognition by its receptor, composed of IL7Rα (interleukin-7 receptor alpha) and TSLPR (TSLP receptor). These genes have been previously associated with other inflammatory diseases. We assessed the genetic association between single nucleotide polymorphisms (SNPs) in TSLP, IL7R and TSLPR and NIUA in Spanish individuals, using genotyped and imputed data. A total of 369 unrelated NIUA patients and 580 NSAID-tolerant control subjects were included, and 6 SNPs in TSLP, 6 in IL7R and 3 in TSLPR were genotyped. Further variants were imputed using Mach and the 1,000 Genomes Project (Phase 3) data. Association testing and statistical analyses were performed with Mach2dat and R. A total of 139 SNPs were tested for association following quality control. Two SNPs in TSLP (rs1816678 and rs764917) showed a nominal association (p = 0.033 and 0.024, respectively) with NIUA, although these results were not statistically significant after correcting for multiple comparisons. Although TSLP, IL7R and TSLPR are important genes involved in the development of the inflammatory response, we found no significant genetic association with NIUA in our population for common SNPs in these genes. © 2016 S. Karger AG, Basel.

  1. Syringomyelia in hereditary multiple exostosis.

    Science.gov (United States)

    Legare, Janet M; Modaff, Peggy; Iskandar, Bermans J; Pauli, Richard M

    2016-11-01

    We describe five children with Hereditary Multiple Exostosis (HME) who also had syringomyelia. Of these, four had a tethered cord/fibrolipoma. No spinal osteochondromas were found in these patients. All had antecedent neurological signs or symptoms that prompted spinal imaging with MRI. Of all patients with HME seen in the Midwest Regional Bone Dysplasia Clinic from 1982 to present, 44% (17/39) of patients had signs or symptoms concerning for possible cord-related neurological findings. However, only 10 of 39 had spinal imaging. Assuming that all individuals with syringomyelia were identified, then 5/39 (13%) were in that way affected. This, of course, is a minimal estimate given that many were not imaged. The incidence of syringomyelia appears to be increased in this population, and seems to be unrelated to spinal osteochondromas. A low threshold for obtaining spinal MRI in patients with Hereditary Multiple Exostosis seems rational. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. 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....

  3. Hereditary aspects of prostate cancer.

    OpenAIRE

    McLellan, D. L.; Norman, R. W.

    1995-01-01

    OBJECTIVE: To review current literature on the hereditary aspects of prostate cancer and to evaluate the importance of family history in history taking and screening for prostate cancer. DATA SOURCES: MEDLINE was searched for articles in English or French published between Jan. 1, 1956, and Oct. 31, 1994, with the use of MeSH headings "prostatic neoplasms," "genetics" and "chromosomes." Additional references were selected from the bibliographies of articles found during the search. STUDY SELE...

  4. Autoimmune thyroid disease as a risk factor for angioedema in patients with chronic idiopathic urticaria: a case-control study

    Directory of Open Access Journals (Sweden)

    Ruy Felippe Brito Gonçalves Missaka

    Full Text Available CONTEXT AND OBJECTIVE: An association between chronic idiopathic urticaria (CIU and autoimmune thyroid disease (ATD has been reported. However, there have not been any reports on whether ATD raises the risk of angioedema, which is a more severe clinical presentation of CIU. Thus, the aim of the present study was to evaluate whether the risk of angioedema is increased in patients with CIU and ATD. DESIGN AND SETTING: Case-control study including 115 patients with CIU at a tertiary public institution. METHODS: The patients were evaluated with regard to occurrence of angioedema and presence of ATD, hypothyroidism or hyperthyroidism. RESULTS: Angioedema was detected in 70 patients (60.9%. There were 22 cases (19.1% of ATD, 19 (16.5% of hypothyroidism and nine (7.8% of hyperthyroidism. The risk among patients with ATD was 16.2 times greater than among those without this thyroid abnormality (confidence interval, CI = 2.07-126.86. The odds ratio for hypothyroidism was 4.6 (CI = 1.00-21.54 and, for hyperthyroidism, 3.3 (CI = 0.38-28.36. CONCLUSIONS: Patients with CIU and ATD presented greater risk of angioedema, which reinforces the idea that a relationship exists between this allergic condition and thyroid autoimmunity. This finding could imply that such patients require specifically directed therapy.

  5. [Hereditary carcinoma: pathogenesis and diagnosis].

    Science.gov (United States)

    Jungck, M

    2000-01-01

    Effective prevention of cancer in patients with a hereditary disposition to malignant tumours was made possible by intensive prevention programs and molecular diagnosis. Taken hereditary non-polyposis colorectal cancer (HNPCC) as an example this article deals with the pathogenesis and molecular diagnosis in hereditary dispositions to cancer. HNPCC is inherited in an autosomal-dominant fashion and caused by germline mutations in genes responsible for detection an removal of DNA-basepair-mismatches (DNA-mismatch-repair-genes). The error rate in DNA replication is reduced thousandfold by these genes. A defective DNA-mismatch-repair results in tumours if the increased mutation rate causes alterations of tumour-suppressor- or oncogenes. HNPCC patients develop colorectal cancer but also tumours of the renal pelvis, the ureter, the small bowel, the endometrium and less often in other organs. The clinical presentation of these tumours may be characteristic, the clinical diagnosis may be guided by different clinical criteria catalogues. The suspicion is proven by the identification of a germline mutation in DNA-mismatch-repair-genes. This laborious diagnostic procedure is often preceded by prescreening procedures as the detection of microsatellite instability or immunohistochemical tests. Once the germline mutation is identified in a affected family member, the first degree relatives may be tested for this mutation. If they have inherited the mutation, they harbour a extremely high risk for developing cancer and therefore may be included in prevention programs. This so called predictive testing must be preceded by genetic counseling.

  6. Oncologic Management of Hereditary Colorectal Cancer

    OpenAIRE

    Yacoub, George; Nagalla, Srikanth; Aklilu, Mebea

    2012-01-01

    Colorectal cancer (CRC) is the second most common cancer in females and the third most common cancer diagnosed in males. Familial CRC comprises ~20 to 30% of all CRC cases. Lynch syndrome (LS), previously called hereditary nonpolyposis CRC (HNPCC), is the most common of the hereditary CRC syndromes. In this review, the oncological management of hereditary colorectal cancer from the medical oncologist perspective is discussed with special emphasis on Lynch syndrome. Lynch syndrome is character...

  7. Disease: H01006 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01006 Hereditary angioedema Hereditary angioedema (HAE) is a rare genetic disorde...r, manifested by recurrent episodes of angioedema localized to the skin or mucosa of the gastrointestinal tr...act or larynx. The laryngeal angioedema is potentially lethal. The classic forms, HAE types I and II, result...6100 PMID:14572810 (description, gene) ... AUTHORS ... Davis AE 3rd ... TITLE ... The pathogenesis of hereditary angioedema... (drug) ... AUTHORS ... Antoniu SA ... TITLE ... Therapeutic approaches in hereditary angioedema. ... JOURNAL ... Clin

  8. Genetics Home Reference: hereditary multiple osteochondromas

    Science.gov (United States)

    ... Health Topic: Benign Tumors Health Topic: Bone Diseases Genetic and Rare Diseases Information Center (1 link) Hereditary multiple osteochondromas Educational Resources (6 links) Cleveland Clinic: ...

  9. Genetics Home Reference: hereditary hemorrhagic telangiectasia

    Science.gov (United States)

    ... Osler-Weber-Rendu syndrome Health Topic: Arteriovenous Malformations Genetic and Rare Diseases Information Center (1 link) Hereditary hemorrhagic telangiectasia Additional NIH Resources (1 link) National ...

  10. SEOM clinical guidelines for hereditary cancer.

    Science.gov (United States)

    Graña, Begoña; Lastra, Enrique; Llort, Gemma; Brunet, Joan; Isla, Dolores

    2011-08-01

    Research in genetics has facilitated the identification of highly penetrant genes responsible for a large number of diseases. In the oncology field, genetic counselling and gene testing are focused on the two most common syndromes in familial cancer: hereditary breast and ovarian cancer syndrome (HBOC) and hereditary non-polyposis colorectal cancer or Lynch syndrome (LS). The objective of this guideline in hereditary cancer is to summarise the current state of knowledge and make recommendations in the areas of diagnosis, prevention and treatment of hereditary cancer.

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

    OpenAIRE

    Liu, Wen-Zhi; Jin, Feng; ZHANG, ZHEN-HAI; Wang, Shu-Bao

    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.

  12. Sociodemographic and clinical characteristics, causal factors and evolution of a group of patients with chronic urticaria-angioedema

    Directory of Open Access Journals (Sweden)

    Maria Regina Cavariani Silvares

    Full Text Available CONTEXT AND OBJECTIVE: Chronic urticaria-angioedema is a common, multiple-cause complaint. The aim was to investigate the sociodemographic and clinical characteristics, causal and aggravating factors and evolution of urticaria-angioedema. DESIGN AND SETTING: This was a descriptive prospective study carried out at the Dermatology outpatient clinic of Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (Unesp. METHODS: A total of 125 patients with chronic urticaria-angioedema were evaluated to obtain sociodemographic data, anamnesis, dermatological and general clinical data and laboratory data, emphasizing causal and aggravating factors and complaint evolution. RESULTS: Chronic urticaria-angioedema occurred mainly in females (mean age: 35 years, but also in men (mean age: 32 years. White color and living in urban areas also predominated. There was no preferential time for symptoms to appear, and nighttime was the most commonly reported time for clinical worsening. Around half of the patients had urticaria associated with angioedema. There were no associated factors in most of the cases, and stress was the most commonly reported aggravating factor. The cause was ascertained in 37.6% of our cases. The mean duration of follow-up was 11.7 months. Around 60% of the patients evolved with the problem under control, 32% improved, 9% had no change in dermatological condition and only one patient worsened. CONCLUSIONS: Chronic urticaria-angioedema was more common among middle-aged women. It is a long-term disease, and its cause was explained in about one-third of the patients. Half of the patients presented disease control after treatment lasting an average of approximately one year.

  13. Sociodemographic and clinical characteristics, causal factors and evolution of a group of patients with chronic urticaria-angioedema.

    Science.gov (United States)

    Silvares, Maria Regina Cavariani; Coelho, Kunie Iabuki Rabello; Dalben, Ivete; Lastória, Joel Carlos; Abbade, Luciana Patrícia Fernandes

    2007-09-06

    Chronic urticaria-angioedema is a common, multiple-cause complaint. The aim was to investigate the sociodemographic and clinical characteristics, causal and aggravating factors and evolution of urticaria-angioedema. This was a descriptive prospective study carried out at the Dermatology outpatient clinic of Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (Unesp). A total of 125 patients with chronic urticaria-angioedema were evaluated to obtain sociodemographic data, anamnesis, dermatological and general clinical data and laboratory data, emphasizing causal and aggravating factors and complaint evolution. Chronic urticaria-angioedema occurred mainly in females (mean age: 35 years), but also in men (mean age: 32 years). White color and living in urban areas also predominated. There was no preferential time for symptoms to appear, and nighttime was the most commonly reported time for clinical worsening. Around half of the patients had urticaria associated with angioedema. There were no associated factors in most of the cases, and stress was the most commonly reported aggravating factor. The cause was ascertained in 37.6% of our cases. The mean duration of follow-up was 11.7 months. Around 60% of the patients evolved with the problem under control, 32% improved, 9% had no change in dermatological condition and only one patient worsened. Chronic urticaria-angioedema was more common among middle-aged women. It is a long-term disease, and its cause was explained in about one-third of the patients. Half of the patients presented disease control after treatment lasting an average of approximately one year.

  14. [Hereditary breast and ovarian cancer].

    Science.gov (United States)

    Lax, S F

    2017-05-01

    Hereditary breast and ovarian carcinomas are frequently caused by germline mutations of the BRCA1 and BRCA2 genes (BRCA1/2 syndromes) and are often less associated with other hereditary syndromes such as Li-Fraumeni and Peutz-Jeghers. The BRCA1/2 proteins have a special role in DNA repair. Therefore, loss of function due to mutation causes an accumulation of mutations in other genes and subsequent tumorigenesis at an early age. BRCA1/2 mutations are irregularly distributed over the length of the genes without hot spots, although special mutations are known. Breast and ovarian cancer occur far more frequently in women with BRCA1/2 germline mutations compared with the general population. Breast cancer occurs increasingly from the age of 30, ovarian cancer in BRCA1 syndrome from the age of 40 and BRCA2 from the age of 50. Suspicion of a BRCA syndrome should be prompted in the case of clustering of breast cancer in 1st degree relatives, in particular at a young age, if breast and ovarian cancer have occurred, and if cases of male breast cancer are known. Breast carcinomas with medullary differentiation seem to predominate in BRCA syndromes, but other carcinoma types may also occur. BRCA germline mutations seem to occur frequently in triple-negative breast carcinomas, whereas an association with ductal carcinoma in situ (DCIS) is rare. Ovarian carcinomas in BRCA syndromes are usually high-grade serous, mucinous carcinomas and borderline tumors are unusual. Pathology plays a special role within the multidisciplinary team in the recognition of patients with hereditary cancer syndromes.

  15. 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...... of putative causal variants and the clinical application of new HBOC genes in cancer risk management and treatment decision-making....... 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...

  16. Hereditary & familial colorectal cancer : Identification, characteristics, surveillance

    NARCIS (Netherlands)

    Kallenberg, F.G.J.

    2017-01-01

    Of all colorectal cancer (CRC) cases, 15-20% is related to familial or hereditary factors. Diagnosing familial and hereditary CRC syndromes is important for several reasons. One of these is that surveillance colonoscopies can reduce CRC incidence and mortality importantly. A complete family history

  17. Hereditary cerebral small vessel disease and stroke

    DEFF Research Database (Denmark)

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

    2017-01-01

    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 of this system...

  18. 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...

  19. Transient angioedema of small bowel secondary to intravenous iodinated contrast medium

    Directory of Open Access Journals (Sweden)

    Kirankumar N Kulkarni

    2014-01-01

    Full Text Available We report the clinical details and imaging findings of a case of transient angioedema of the small bowel following intravenous administration of non-ionic iodinated contrast material in a 17 year old female with no predisposing risk factors. Findings included long segment, symmetric, circumferential, low-density, bowel wall thickening involving the duodenum, jejunum, and most of the ileum on computed tomography scan obtained at 7 min following intravenous contrast material injection. This entity is self-limiting with a favourable clinical outcome and requires no specific treatment but only aggressive clinical monitoring.

  20. [Facial and oropharyngeal angioedema in patient with alimentary fish allergy. Diagnosis and treatment].

    Science.gov (United States)

    Pino Rivero, V; Rodríguez Carmona, M; Iglesias González, R J; del Castillo Beneyto, F

    2007-01-01

    Vegetal or animal food can produce hipersensibility reactions IgE mediated of diverse intensity. We report the case of a 54 years old woman without previous allergic antecedents who after eating frozen fish had to go to Emergencies due to angioedema especially in face and oropharynx. The ENT exploration by fibroscopia descarted laryngeal edema but the patient showed initially respiratory symptoms so she was treated with SC adrenalina and then steroids during her admission. The diagnosis of alimentary alergia would be confirmed after by Allergology with cutaneous test prick type.

  1. Allergic contact dermatitis mimicking angioedema due to paraphenylendiamine hypersensitivity: a case report.

    Science.gov (United States)

    Tukenmez Demirci, Gulsen; Kivanc Altunay, Ilknur; Atis, Guldehan; Kucukunal, Asli

    2012-09-01

    Active sensitization to paraphenylendiamine (PPD) and related compounds from temporary black henna tattoos has become an epidemic in the recent years. Hair dyes also include PPD like black henna tatoos which cause allergic contact dermatitis. Skin lesions of allergic contact dermatitis from PPD are mostly seen as an exudative erythema, an erythema multiforme-like eruption or a bullous contact dermatitis. We, herein, report a 27 year-old woman with an angioedema-like reaction occurring after the first exposure to hair dye who was unaware of being previously sensitized to PPD from black henna tattoo.

  2. The molecular classification of hereditary endocrine diseases.

    Science.gov (United States)

    Ye, Lei; Ning, Guang

    2015-12-01

    Hereditary endocrine diseases are an important group of diseases with great heterogeneity. The current classification for hereditary endocrine disease is mostly based upon anatomy, which is helpful for pathophysiological interpretation, but does not address the pathogenic variability associated with different underlying genetic causes. Identification of an endocrinopathy-associated genetic alteration provides evidence for differential diagnosis, discovery of non-classical disease, and the potential for earlier diagnosis and targeted therapy. Molecular diagnosis should be routinely applied when managing patients with suspicion of hereditary disease. To enhance the accurate diagnosis and treatment of patients with hereditary endocrine diseases, we propose categorization of endocrine diseases into three groups based upon the function of the mutant gene: cell differentiation, hormone synthesis and action, and tumorigenesis. Each category was further grouped according to the specific gene function. We believe that this format would facilitate practice of precision medicine in the field of hereditary endocrine diseases.

  3. Phenotype standardization of angioedema in the head and neck region caused by agents acting on the angiotensin system

    NARCIS (Netherlands)

    Wadelius, M.; Marshall, S. E.; Islander, G.; Nordang, L.; Karawajczyk, M.; Yue, Q.-Y.; Terreehorst, I.; Baranova, E. V.; Hugosson, S.; Sköldefors, K.; Pirmohamed, M.; Maitland-van der Zee, A.-H.; Alfirevic, A.; Hallberg, P.; Palmer, C. N. A.

    2014-01-01

    Angioedema is a potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. To study the genetic etiology of this rare adverse event, international consortia and multicenter recruitment of patients are needed. To reduce patient

  4. Determinants of angiotensin-converting enzyme inhibitor (ACEI) intolerance and angioedema in the UK Clinical Practice Research Datalink

    NARCIS (Netherlands)

    Mahmoudpour, Seyed Hamidreza; Baranova, Ekaterina Vitalievna; Souverein, Patrick C; Asselbergs, Folkert W; de Boer, Anthonius; Maitland-van der Zee, Anke Hilse

    2016-01-01

    AIM: The aim of the present study was to describe the occurrence and determinants of angiotensin-converting enzyme (ACE) inhibitor (ACEI) intolerance and angioedema (AE) among patients initiating ACEI therapy in a real-world primary care population. METHODS: Two nested case-control studies were

  5. Angioedema adquirido autoimune de difícil controle em paciente com lúpus eritematoso sistêmico Intractable acquired autoimmune angioedema in a patient with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Vilson Furlanetto Junior

    2010-02-01

    Full Text Available O angioedema adquirido é causado por diferentes medicamentos e doenças linfoproliferativas, e tem sido raramente relacionado com a presença de doenças autoimunes. Descrevemos aqui uma paciente de 47 anos com lúpus eritematoso sistêmico (LES com envolvimento cutâneo importante que desenvolveu angioedema recorrente localizado em face incluindo lábios e pálpebras, membros superiores e tórax, não acompanhado de urticária e com dosagem do inibidor de C1 esterase reduzida. A utilização de antimaláricos, glicocorticoides e pulsoterapia com metilprednisolona associada ao uso de azatioprina não determinou melhora. A paciente utilizou também danazol sem sucesso, e apresentou resposta clínica somente após ter sido submetida a múltiplas sessões de plasmaferese, ocorrendo inclusive resolução de extenso angioedema na mucosa do trato gastrointestinal.Acquired angioedema is caused by different drugs and lymphoproliferative diseases, and rarely it has also been related to the presence of auto-immune disorders. We report the case of a 47 year old female with systemic lupus erythematosus (SLE and severe cutaneous involvement who developed recurrent localized angioedema of the face, including lips and eye lids, upper limbs, and thorax, not associated with urticaria, and with reduced levels of C1 esterase inhibitor. Treatment with antimalarials, glucocorticoids, and pulse therapy with methylprednisolone associated with azathioprine did not improve her condition. The patient was also unsuccessfully treated with danazol, and she only showed clinical response after several sessions of plasmapheresis, including resolution of the extensive edema of the gastrointestinal tract.

  6. Utility of routine laboratory testing in management of chronic urticaria/angioedema.

    Science.gov (United States)

    Tarbox, James A; Gutta, Ravi C; Radojicic, Cristine; Lang, David M

    2011-09-01

    Laboratory tests are routinely ordered to identify or rule out a cause in patients with chronic urticaria/angioedema (CUA). The results of these tests are usually within normal limits or unremarkable. To investigate the proportion of abnormal test results in patients with CUA leading to a change in management and in outcomes of care. Retrospective analysis of a random sample of adult patients with CUA from 2001-2009. Cases totaled 356: 166 with urticaria and angioedema (AE), 187 with urticaria, and 3 with only AE. Patients were predominately women (69.1%) and white (75.6%), with a mean age of 48 ± 15 years. Abnormalities were commonly seen in complete blood counts (34%) and in complete metabolic panels (9.4%). Among the 1,872 tests that were ordered, results of 319 (17%) were abnormal. Of 356 patients, 30 underwent further testing because of abnormalities in laboratory work. This represented 30 of 1,872 tests (1.60%). Only 1 patient benefited from a subsequent change in management. Laboratory testing in CUA patients referred for an Allergy and Immunology evaluation rarely lead to changes in management resulting in improved outcomes of care. Copyright © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. Eruption of urticaria and angioedema induced by binging and purging in an anorexia nervosa patient.

    Science.gov (United States)

    Latzer, Itay Tokatly; Agmon-Levin, Nancy; Somech, Raz; Stein, Daniel

    2016-08-01

    Anorexia nervosa is a perplexing psycho-biological disorder with a systemic nature, which can present in almost every organ and system of the body. Among the different presentations of starvation, several immunological and dermatological manifestations have been documented. To the best of our knowledge the occurrence of urticaria and angioedema in patients with binge or purge behaviors has yet to be documented. We present a 16-year-old female patient diagnosed with anorexia nervosa binge/purge type, who presented with urticaria and angioedema shortly after binge/purge episodes that subsided when these behaviors ceased. Other possible causes for the urticaria were ruled out. This finding may represent a form of inducible urticaria, exacerbated in low-weight patients by the occurrence of binge/purge behaviors. We wish to report this observation in an attempt to widen the scope of the physical signs that may accompany eating disorders and bring this specific phenomenon into awareness. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:822-825). © 2016 Wiley Periodicals, Inc.

  8. Recurrent Laryngeal Edema Imitating Angioedema Caused by Dislocated Screw after Anterior Spine Surgery

    Directory of Open Access Journals (Sweden)

    Piotr Wójtowicz

    2015-01-01

    Full Text Available The anterior cervical spine surgery is a common procedure to stabilize vertebrae damaged by various diseases. The plates and screws are usually used in the spine fixation. This kind of instrumentation may detach from the bones which is a rare but well-known complication. A 77-year-old male presented to the otorhinolaryngology department with throat pain, choking, and dysphagia. At first the angioedema was diagnosed and he was treated conservatively. The endoscopy revealed laryngeal edema, being more defined on the right side with right vocal fold paresis. CT scans showed the stabilizing plate with two screws attached tightly and the back-out of the third screw toward soft tissue of the neck. In the meantime, his condition deteriorated and he needed tracheotomy. In few days the surgical removal of the dislocated screw was performed successfully. Although two-month follow-up reported no obstruction of the larynx, the vocal folds paresis with gradual functional improvement was observed. Long-term complication of anterior spine surgery sometimes may suggest laryngeal angioedema at first. If the conservative treatment is ineffective and there is a history of anterior spine surgery, the clinicians should consider the displacement of the plate or screws in differential diagnosis.

  9. A Case of Miller Fisher Syndrome, Thromboembolic Disease, and Angioedema: Association or Coincidence?

    Science.gov (United States)

    Salehi, Nooshin; Choi, Eric D; Garrison, Roger C

    2017-01-16

    BACKGROUND Miller Fisher Syndrome is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia, and is considered to be a variant of Guillain-Barre Syndrome. Miller Fisher Syndrome is observed in approximately 1-5% of all Guillain-Barre cases in Western countries. Patients with Miller Fisher Syndrome usually have good recovery without residual deficits. Venous thromboembolism is a common complication of Guillain-Barre Syndrome and has also been reported in Miller Fisher Syndrome, but it has generally been reported in the presence of at least one prothrombotic risk factor such as immobility. A direct correlation between venous thromboembolism and Miller Fisher Syndrome or Guillain-Barre Syndrome has not been previously described. CASE REPORT We report the case of a 32-year-old Hispanic male who presented with acute, severe thromboembolic disease and concurrently demonstrated characteristic clinical features of Miller Fisher Syndrome including ophthalmoplegia, ataxia, and areflexia. Past medical and family history were negative for thromboembolic disease, and subsequent hypercoagulability workup was unremarkable. During the course of hospitalization, the patient also developed angioedema. CONCLUSIONS We describe a possible association between Miller Fisher Syndrome, thromboembolic disease, and angioedema.

  10. [Epidemiology of monogenic hereditary diseases in Rostov oblast: population dynamic factors determining the differentiation of the load of hereditary diseases in eight districts].

    Science.gov (United States)

    Zinchenko, R A; Amelina, S S; Shokarev, R A; Val'kov, R A; Val'kova, T I; Vetrova, N V; Kriventsova, N V; El'chinova, G I; Petrova, N V; Khlebnikova, O V

    2009-04-01

    Analysis of the diversity of monogenic hereditary diseases in eight raions (districts) of Rostov oblast (region) of Russia (Tsimlyansk, Volgodonskoi, Tselina, Egorlykskaya, Millerovo, Tarasovskaya, Rodionovo-Nesvetaiskaya, and Matveevo-Kurgan raions) has been summarized. The total sample size was 320925 subjects. The spectrum of hereditary diseases detected in the eight districts comprises 187 diseases, including 99 autosomal dominant (AD), 72 autosomal recessive (AR), and 16 X-linked diseases. The mean prevalence rate of each disease in the total population has been calculated. Accumulation of individual diseases in different regions of Rostov oblast has been calculated; the disease accumulation has been compared with that in some populations of Russia examined earlier. Cluster analysis using the data on the frequencies of genes of hereditary diseases has shown the gene geographic position of the Rostov oblast population among the following ethnic populations of Russia: Russians (Kostroma, Kirov, and Rostov oblasts and Krasnodar krai), Chuvashes (Chuvashia), Adygeans (Adygea), Maris (Marii El), and Udmurts (Udmurtia).

  11. Hereditary colorectal cancer syndromes and genetic testing.

    Science.gov (United States)

    Macaron, Carole; Leach, Brandie H; Burke, Carol A

    2015-01-01

    Colorectal cancer (CRC) is a leading cause of cancer and cancer deaths in the Western world. Approximately 5-10% of CRC are hereditary, due to a defined genetic cause. Individuals and families affected with a hereditary CRC syndrome exhibit benign and malignant extra-intestinal tumors, require aggressive cancer screening and benefit from management by a multi-disciplinary team of professionals. The clinical manifestations, genetic causes and current management of patients with hereditary colon cancer syndrome is provided. © 2014 Wiley Periodicals, Inc.

  12. Phenotypic heterogeneity of hereditary gynecologic cancers: a report from the Creighton hereditary cancer registry.

    Science.gov (United States)

    Casey, Murray Joseph; Bewtra, Chhanda; Lynch, Henry T; Snyder, Carrie; Stacy, Mark; Watson, Patrice

    2013-12-01

    To determine the validity of observations suggesting a significant dichotomy of gynecologic cancers determined by linkage to specific genetic defects associated with two major autosomal dominant hereditary cancer syndromes; the Creighton University Hereditary Cancer Registry was searched for female carriers of germ line mutations in BRCA1 and BRCA2, associated with the Hereditary Breast Ovarian Cancer syndrome, and in the mismatch repair (MMR) genes MLH1, MSH2 and MSH6, associated with Lynch syndrome, who were registered with invasive uterine, ovarian, fallopian tube or peritoneal cancers between January 1, 1959 and December 31, 2010. From 217 such cases, a total of 174 subjects, consisting of 95 BRCA1 and BRCA2 mutation carriers and 79 carriers of mutations in MMR genes, were identified who had current signed Health Insurance Portability and Accountability Act forms and complete primary diagnostic pathology reports and clinical records. Data meticulously extracted from these cases were categorized and statistically analyzed. There were highly significant differences between carriers of BRCA1 and BRCA2 mutations and carriers of MMR gene mutations in the proportion of serous carcinomas compared with endometrioid carcinomas of the uterus, including cervix and endometium (p cancers (p cancer, and endometrioid carcinoma was found in two of four MMR gene mutation carriers with fallopian tube cancers. All other fallopian tube cancers were serous carcinomas. Seven BRCA1 and one BRCA2 mutation carriers were diagnosed with primary peritoneal serous carcinoma; no peritoneal carcinomas were registered in MMR gene mutation carriers. Nine of 14 gynecologic cancers with associated endometriosis in mutation carriers were endometrioid or endometrioid mixed carcinomas compared with just three of other histologic types. Primary breast cancers, that characterize the HBOC syndrome, were much more frequent in BRCA1 and BRCA2 mutation carriers; while multiple gynecologic cancers and

  13. Diagnostic Approach to Hereditary Colorectal Cancer Syndromes

    Science.gov (United States)

    Kalady, Matthew F.; Heald, Brandie

    2015-01-01

    Approximately 5 to 10% of colorectal cancers develop within a known hereditary syndrome. Specific underlying genetic mutations drive the clinical phenotype and it is imperative to determine the genetic etiology to provide meaningful surveillance and intervention. Recognizing potential patients and families with a hereditary predisposition is the first step in management. Syndromes can be categorized according to polyp burden as polyposis or nonpolyposis. Clinical assessment should start with a personal and family medical history, physical examination, and evaluation for the presence and type of colorectal polyps or cancers. Key information is gained from these simple steps and should guide the specific genetic analysis for diagnosis. Genetic counseling is a critical component to any hereditary colorectal cancer program and should be conducted before genetic testing to provide education about the implications of test results. This review focuses on the thought process that drives initial clinical evaluation and guides genetic testing for patients with suspected hereditary colorectal cancer syndromes. PMID:26664327

  14. 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...

  15. 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 ...

  16. [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

  17. Genetics Home Reference: hereditary antithrombin deficiency

    Science.gov (United States)

    ... may have an increased risk for pregnancy loss (miscarriage) or stillbirth. Related Information What does it mean ... Meer J. High long-term absolute risk of recurrent venous thromboembolism in patients with hereditary deficiencies of ...

  18. The Genetics Of Blood Disorders: Hereditary Hemoglobinopathies.

    OpenAIRE

    Sonati M.F.; Costa F.F.

    2015-01-01

    Objective: To summarize recently published data on the pathophysiology, diagnosis and treatment of sickle cell diseases and β-Thalassemias, the most relevant hereditary hemoglobinopathies in the global population. Sources: Searches were run on the MEDLINE and SCIELO databases, limited to the period from 2003 to May 2008, using the terms hereditary hemoglobinopathies, sickle cell diseases and β-thalassemia. Two books and two chapters were also included. Summary of the findings: More than 2,000...

  19. 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.

  20. A Review of Hereditary Fructose Intolerance

    OpenAIRE

    Mogoş Tiberius; Iacobini Andra Evelin

    2016-01-01

    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...

  1. [Consensus on hereditary cancer between the Spanish Oncology Society and the primary care societies].

    Science.gov (United States)

    Robles, L; Balmaña, J; Barrel, I; Grandes, S; Graña, B; Guillén, C; Marcos, H; Ramírez, D; Redondo, E; Sánchez, J

    2013-01-01

    It is believed that 5% of all cancers are hereditary, on being caused by mutations in the germinal line in cancer susceptibility genes. The hereditary pattern in the majority of cases is autosomal dominant. Genetic tests are only recommended to individuals whose personal or family history is highly suggestive of a hereditary cancer. The appropriate assessment of these individuals and their families must be performed in Cancer Genetic Counselling Units (UCGC). Representatives of the Spanish Medical Oncology Society (Sociedad Española de Oncología Médica [SEOM]) and the three primary care scientific societies: Spanish Society of Family and Community Medicine (Sociedad Española de Medicina de Familia y Comunitaria [SEMFyC]), Spanish Society of Primary Care Physicians (Sociedad Española de Médicos de Atención Primaria [SEMERGEN]) and the Spanish Society of General and Family Doctors (Sociedad Española de Médicos Generales y de Familia [SEMG]), met to prepare this consensus document on hereditary cancer. The consensus identified the three main aspects: how to identify subjects at risk of hereditary cancer; how to refer to a UCGC; and the usefulness of the assessment and genetic studies. A document, with the text fully agreed by all the participants, has been prepared. It contains a summary of the principal characteristics of the care for individuals with hereditary cancer. It shows how to; identify them, assess them, refer them to a UCGC. How to assess their genetic risk, perform genetic studies, as well as prevention measures and reduction of the risk is also presented. This consensus document is a landmark in the relationships with several Scientific Societies that represent the professionals who provide care to individuals with cancer and their families, and will help to improve care in hereditary cancer in Spain. Copyright © 2013. Publicado por Elsevier España.

  2. Hereditary autoinflammatory syndromes : with emphasis on hyper-IgD and periodic fever syndrome

    NARCIS (Netherlands)

    Simon, A.

    2004-01-01

    The subject of this thesis is a group of rare hereditary disorders, collectively called auto-inflammatory syndromes, with a specific focus on the hyper-IgD and periodic fever syndrome. The autoinflammatory syndromes are characterized by lifelong recurrent episodes with fever, usually accompanied by

  3. The Design of Studies to Evaluate Hereditary and Environmental Contributions to the Etiology of Behavioral Disorders.

    Science.gov (United States)

    Rosenthal, David

    The introductory discussion focuses on the change in the current scientific climate regarding the role of heredity in the etiology of behavioral disorders. The author and his colleagues embarked on a series of studies, using naturally occurring adoptions as their subject source, to tease apart hereditary and environmental factors thought to be…

  4. Hereditary sensory neuropathy type I

    Science.gov (United States)

    Auer-Grumbach, Michaela

    2008-01-01

    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 neuropathy, or decaying skin

  5. 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

  6. Acutely Onset Amiodarone-Induced Angioedema in a Patient with New Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Hossein Vakili

    2014-01-01

    Full Text Available A 50-year-old man was admitted to our emergency department due to new episode of palpitation. He had history of angioplasty of right coronary artery (RCA with drug eluting stent 2 years ago. His electrocardiogram revealed atrial fibrillation (AF. Intravenous amiodarone 150 mg during 10 minutes and then 1 mg/min infusion were started to achieve rate control and pharmacologic conversion to sinus rhythm. After 60 minutes of starting amiodarone infusion, he developed swelling of the skin around his mouth and eyes, and also mucosa of the mouth, eyes and tongue. To conclude, angioedema should be considered a rare side effect of amiodarone which is used broadly in cardiovascular field.

  7. Hereditary Predispositions to Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Sarah A. Bannon

    2016-05-01

    Full Text Available Myelodysplastic syndromes (MDS are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e.g., Fanconi anemia (FA, dyskeratosis congenita (DC, Diamond–Blackfan anemia (DBA, and Shwachman–Diamond syndrome (SBS, hallmarked by clinically-recognizable phenotypes (e.g., radial ray anomalies in FA and significantly increased risks for MDS and/or acute myeloid leukemia (AML in the setting of bone marrow failure. However, additional families with multiple cases of MDS or AML have long been reported in the medical literature with little known regarding potential hereditary etiologies. Over the last decade, genomic investigation of such families has revealed multiple genes conferring inherited risks for MDS and/or AML as the primary malignancy, including RUNX1, ANKRD26, DDX41, ETV6, GATA2, and SRP72. As these syndromes are increasingly appreciated in even apparently de novo presentations of MDS, it is important for hematologists/oncologists to become familiar with these newly-described syndromes. Herein, we provide a review of familial MDS syndromes and practical aspects of management in patients with predisposition syndromes.

  8. Hereditary Portfolio Optimization with Taxes and Fixed Plus Proportional Transaction Costs—Part II

    Directory of Open Access Journals (Sweden)

    Mou-Hsiung Chang

    2007-01-01

    Full Text Available This paper is the continuation of the paper entitled “Hereditary portfolio optimization with taxes and fixed plus proportional transaction costs I” that treats an infinite-time horizon hereditary portfolio optimization problem in a market that consists of one savings account and one stock account. Within the solvency region, the investor is allowed to consume from the savings account and can make transactions between the two assets subject to paying capital-gain taxes as well as a fixed plus proportional transaction cost. The investor is to seek an optimal consumption-trading strategy in order to maximize the expected utility from the total discounted consumption. The portfolio optimization problem is formulated as an infinite dimensional stochastic classical impulse control problem due to the hereditary nature of the stock price dynamics and inventories. This paper contains the verification theorem for the optimal strategy. It also proves that the value function is a viscosity solution of the QVHJBI.

  9. Late-onset Leber hereditary optic neuropathy.

    Science.gov (United States)

    Pfeiffer, Margaret L; Hashemi, Nafiseh; Foroozan, Rod; Lee, Andrew G

    2013-01-01

    While Leber hereditary optic neuropathy typically causes bilateral visual loss in the second through fourth decades, we highlight visual loss from Leber hereditary optic neuropathy in older patients to characterize the clinical features of this cohort. Retrospective case series. Patients seen between January 2003 and July 2012 at Baylor College of Medicine and between April 2010 and July 2012 at The Methodist Hospital in Houston, Texas. Patients with visual loss from genetically confirmed Leber hereditary optic neuropathy were identified via retrospective chart review. Clinical courses of patients. Five patients with visual loss from genetically confirmed Leber hereditary optic neuropathy were greater than 60 years of age at the time of visual loss (range 62-70 years, mean 66.4 ± 3.0). This series reinforces the importance of including Leber hereditary optic neuropathy in the differential diagnosis of patients of any age with optic neuropathy. © 2013 The Authors. Clinical and Experimental Ophthalmology © 2013 Royal Australian and New Zealand College of Ophthalmologists.

  10. A patient with steroids and antihistaminic drug allergy and newly occurred chronic urticaria angioedema: what about omalizumab?

    Science.gov (United States)

    Kutlu, A; Karabacak, E; Aydin, E; Ozturk, S; Bozkurt, B

    2014-08-01

    In this case report, successful use of omalizumab in the treatment of chronic urticarial and angioedema in a 24-year-old female patient with an allergic reaction history to almost every drug including steroids and antihistamines was presented. She also had allergy against a large number of foods, which were confirmed by oral provocation, specific Immunoglobulin E and allergy skin test. © The Author(s) 2014.

  11. Genetics Home Reference: distal hereditary motor neuropathy, type V

    Science.gov (United States)

    ... neuropathy, type V Distal hereditary motor neuropathy, type V Printable PDF Open All Close All Enable Javascript ... collapse boxes. Description Distal hereditary motor neuropathy, type V is a progressive disorder that affects nerve cells ...

  12. The Korean Hereditary Breast Cancer Study: Review and Future Perspectives

    National Research Council Canada - National Science Library

    Kang, Eunyoung; Kim, Sung-Won

    2013-01-01

    .... In 2007, the Korean Hereditary Breast Cancer (KOHBRA) Study was established to obtain evidence for the accurate risk assessment and management of hereditary breast and ovarian cancer (HBOC) in Korea...

  13. 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.

  14. The metabolomic signature of Leber's hereditary optic neuropathy reveals endoplasmic reticulum stress.

    Science.gov (United States)

    Chao de la Barca, Juan Manuel; Simard, Gilles; Amati-Bonneau, Patrizia; Safiedeen, Zainab; Prunier-Mirebeau, Delphine; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Gueguen, Naïg; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Ferré, Marc; Bris, Céline; Kouassi Nzoughet, Judith; Bocca, Cinzia; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Lenaers, Guy; Martinez, M Carmen; Procaccio, Vincent; Reynier, Pascal

    2016-11-01

    Leber's hereditary optic neuropathy (MIM#535000), the commonest mitochondrial DNA-related disease, is caused by mutations affecting mitochondrial complex I. The clinical expression of the disorder, usually occurring in young adults, is typically characterized by subacute, usually sequential, bilateral visual loss, resulting from the degeneration of retinal ganglion cells. As the precise action of mitochondrial DNA mutations on the overall cell metabolism in Leber's hereditary optic neuropathy is unknown, we investigated the metabolomic profile of the disease. High performance liquid chromatography coupled with tandem mass spectrometry was used to quantify 188 metabolites in fibroblasts from 16 patients with Leber's hereditary optic neuropathy and eight healthy control subjects. Latent variable-based statistical methods were used to identify discriminating metabolites. One hundred and twenty-four of the metabolites were considered to be accurately quantified. A supervised orthogonal partial least squares discriminant analysis model separating patients with Leber's hereditary optic neuropathy from control subjects showed good predictive capability (Q 2cumulated = 0.57). Thirty-eight metabolites appeared to be the most significant variables, defining a Leber's hereditary optic neuropathy metabolic signature that revealed decreased concentrations of all proteinogenic amino acids, spermidine, putrescine, isovaleryl-carnitine, propionyl-carnitine and five sphingomyelin species, together with increased concentrations of 10 phosphatidylcholine species. This signature was not reproduced by the inhibition of complex I with rotenone or piericidin A in control fibroblasts. The importance of sphingomyelins and phosphatidylcholines in the Leber's hereditary optic neuropathy signature, together with the decreased amino acid pool, suggested an involvement of the endoplasmic reticulum. This was confirmed by the significantly increased phosphorylation of PERK and eIF2α, as well as

  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. Therapeutic Strategies for Hereditary Kidney Cancer.

    Science.gov (United States)

    Sidana, Abhinav; Srinivasan, Ramaprasad

    2016-08-01

    The study of hereditary forms of kidney cancer has vastly increased our understanding of metabolic and genetic pathways involved in the development of both inherited and sporadic kidney cancers. The recognition that diverse molecular events drive different forms of kidney cancers has led to the preclinical and clinical development of specific pathway-directed strategies tailored to treat distinct subgroups of kidney cancer. Here, we describe the molecular mechanisms underlying the pathogenesis of several different types of hereditary renal cancers, review their clinical characteristics, and summarize the treatment strategies for the management of these cancers.

  17. 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.

  18. [Recurrent urinary lithiasis revealing hereditary xanthinuria].

    Science.gov (United States)

    Bahlous, Afef; Gasmi, Manef; Mohsni, Amira; Abdelmoula, Jaouida

    2007-09-01

    Hereditary xanthinuria, due to a purine metabolism disorder, is a rare cause of urinary lithiasis in children. We report the case of a child aged 3 and a half years, who presented recurrent urinary lithiasis that led to destruction of the right kidney. Infrared spectrophotometric analysis of the calculus concluded that it was composed of 100% xanthine. Laboratory tests showed hypouricemia and hypouricosuria with elevated urinary excretion of oxypurines. These findings led to a diagnosis of hereditary xanthinuria. Early diagnosis of this rare disease is essential to avoid its complications. Metabolic causes must be sought in children with lithiasis.

  19. Analysis of mutations in the SOS-1 gene in two Polish families with hereditary gingival fibromatosis.

    Science.gov (United States)

    Gawron, K; Bereta, G; Nowakowska, Z; Łazarz-Bartyzel, K; Potempa, J; Chomyszyn-Gajewska, M; Górska, R; Plakwicz, P

    2017-10-01

    To establish whether two families from Malopolska and Mazovia provinces in Poland are affected by hereditary gingival fibromatosis type 1, caused by a single-cytosine insertion in exon 21 of the Son-of-Sevenless-1 gene. Six subjects with hereditary gingival fibromatosis and five healthy subjects were enrolled in the study. Gingival biopsies were collected during gingivectomy or tooth extraction and used for histopathological evaluation. Total RNA and genomic DNA were purified from cultured gingival fibroblasts followed by cDNA and genomic DNA sequencing and analysis. Hereditary gingival fibromatosis was confirmed by periodontal examination, X-ray, and laboratory tests. Histopathological evaluation showed hyperplastic epithelium, numerous collagen bundles, and abundant-to-moderate fibroblasts in subepithelial and connective tissue. Sequencing of exons 19-22 of the Son-of-Sevenless-1 gene did not reveal a single-cytosine insertion nor other mutations. Patients from two Polish families under study had not been affected by hereditary gingival fibromatosis type 1, caused by a single-cytosine insertion in exon 21 of the Son-of-Sevenless-1 gene. Further studies of the remaining regions of this gene as well as of other genes are needed to identify disease-related mutations in these patients. This will help to unravel the pathogenic mechanism of gingival overgrowth. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  20. Approaches to the diagnosis and management of patients with a history of nonsteroidal anti-inflammatory drug-related urticaria and angioedema.

    Science.gov (United States)

    Kowalski, Marek L; Woessner, Katharine; Sanak, Marek

    2015-08-01

    Nonsteroidal anti-inflammatory drug (NSAID)-induced urticarial and angioedema reactions are among the most commonly encountered drug hypersensitivity reactions in clinical practice. Three major clinical phenotypes of NSAID-induced acute skin reactions manifesting with angioedema, urticaria, or both have been distinguished: NSAID-exacerbated cutaneous disease, nonsteroidal anti-inflammatory drug-induced urticaria/angioedema (NIUA), and single NSAID-induced urticaria and angioedema. In some patients clinical history alone might be sufficient to establish the diagnosis of a specific type of NSAID hypersensitivity, whereas in other cases oral provocation challenges are necessary to confirm the diagnosis. Moreover, classification of the type of cutaneous reaction is critical for proper management. For example, in patients with single NSAID-induced reactions, chemically nonrelated COX-1 inhibitors can be safely used. However, there is cross-reactivity between the NSAIDs in patients with NSAID-exacerbated cutaneous disease and NIUA, and thus only use of selective COX-2 inhibitors can replace the culprit drug if the chronic treatment is necessary, although aspirin desensitization will allow for chronic treatment with NSAIDs in some patients with NIUA. In this review we present a practical clinical approach to the patient with NSAID-induced urticaria and angioedema. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. [Preventive resection of hereditary diffuse gastric cancer

    NARCIS (Netherlands)

    Hoogerbrugge-van der Linden, N.; Ligtenberg, M.J.L.; Nagengast, F.M.; Bonenkamp, J.J.; Krieken, J.H.J.M. van

    2006-01-01

    Hereditary diffuse gastric cancers are rare, accounting for at most 1-3% of gastric cancers. It can be caused by a mutation in the tumour-suppressor gene CDH1. A healthy person carrying a CDH1 mutation has a cumulative risk of developing gastric cancer of 70-80%. In most cases, gastric cancer is

  2. Hereditary spherocytosis. | Hassan | Annals of African Medicine

    African Journals Online (AJOL)

    Hereditary spherocytosis (HS) is a familial hemolytic disorder with marked heterogeneity of clinical features, ranging from an asymptomatic condition to a fulminant hemolytic anemia. Although a positive family history of spherocytosis increases the risk for this disorder, it may be sporadic in some cases. In severe cases the ...

  3. Presumed hereditary retinal degenerations: Ibadan experience ...

    African Journals Online (AJOL)

    Background: Retinitis pigmentosa (RP) is a hereditary retinal degenerative condition with no known treatment. Associated ocular conditions, such as cataract and glaucoma, when present further worsen vision, but these conditions are often treatable. There are, however, no known reports of cataract or glaucoma surgery in ...

  4. 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

  5. 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.

  6. Hereditary spectrin deficiency in Golden Retriever dogs

    NARCIS (Netherlands)

    Slappendel, Robbert J.; van Zwieten, Rob; van Leeuwen, Martin; Schneijdenberg, Chris T. W. M.

    2005-01-01

    Spectrin deficiency with increased erythrocyte osmotic fragility (OF) is a hallmark of hereditary spherocytosis, which is the most common congenital hemolytic anemia in humans of northern European ancestry. A radioimmunoassay revealed that erythrocyte spectrin concentration was 50-65% of normal in 5

  7. 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

  8. 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

  9. Severe angioedema in myxedema coma: a difficult airway in a rare endocrine emergency.

    Science.gov (United States)

    Lee, Christopher H; Wira, Charles R

    2009-10-01

    Myxedema coma is the most lethal manifestation of hypothyroidism. It is a true medical emergency and can result in profound hemodynamic instability and airway compromise. Myxedema coma currently remains a diagnostic challenge due to the rarity of cases seen today, and failure to promptly initiate therapy with replacement thyroid hormone can be fatal. As thyroid hormone therapy can take days or weeks to reverse the manifestations of myxedema coma, interim supportive therapy is critical while awaiting clinical improvement. Some patients will require endotracheal intubation in the emergency department (ED), and physicians should be aware that unanticipated posterior pharyngeal edema in myxedema coma could severely complicate airway management. Although mechanical ventilation is a well-described adjunctive therapy for myxedema coma, reports of the potential difficulty in securing a definitive airway in these patients are rare. We describe a case of an unidentified woman who presented to the ED with myxedema coma requiring urgent endotracheal intubation and was found to have extensive posterior pharyngeal angioedema inconsistent with her relatively benign external examination. This case highlights the typical features of myxedema coma and discusses our necessity for a rescue device in definitive endotracheal tube placement. Emergency physicians should anticipate a potentially difficult airway in all myxedema coma patients regardless of the degree of external facial edema present.

  10. Type I anaphylactic reaction due to contrast induced angioedema causing neck swelling: the role of sitting fiberoptic bronchoscopy in emergent intubation

    Directory of Open Access Journals (Sweden)

    Ali Dabbagh

    2016-07-01

    Full Text Available Contrast induced angioedema is a rapidly progressive state involving a number of organ systems including the upper airway tract; which is usually a type I anaphylactic reaction also known as immediate hypersensitivity reaction. Prompt preservation of the respiratory tract is the cornerstone of this situation. The use of fiberoptic bronchoscope for tracheal intubation though very helpful, has some special considerations due to the anatomic distortions created by edema.This manuscript describes a patient with contrast induced angioedema managed successfully. Serum levels of IgE were highly increased during the first hours after the event; while serum levels of complement were normal. However, rapid airway management and prophylactic intubation saved the patient and prevented the possible aftermath of airway obstruction.Keywords: airway management; type I anaphylactic reaction, angioedema; fiberoptic bronchoscope.Conflict of interest: none of the authors has any conflict of interest.

  11. Facial Oedema Is Not Always Angioedema: A Case of Spontaneous Pneumomediastinum with Subcutaneous Emphysema during COPD Exacerbation

    Directory of Open Access Journals (Sweden)

    Sarah Damanti

    2015-10-01

    Full Text Available We report a case of acute facial oedema in an elderly hospitalized patient which was initially misdiagnosed as angioedema secondary to antibiotics in a patient with an allergic diathesis. We describe the differential aetiologies and then the true cause of the oedema, which was an uncommon complication of a very common condition in the elderly: a pneumomediastinum with subcutaneous emphysema probably due to rupture of an emphysematous lung bulla during chronic obstructive pulmonary disease (COPD exacerbation. Lastly, we focus on the therapeutic procedures instituted for the treatment of the pneumomediastinum.

  12. Hereditary Spastic Paraplegia: Clinical and Genetic Hallmarks.

    Science.gov (United States)

    de Souza, Paulo Victor Sgobbi; de Rezende Pinto, Wladimir Bocca Vieira; de Rezende Batistella, Gabriel Novaes; Bortholin, Thiago; Oliveira, Acary Souza Bulle

    2017-04-01

    Hereditary spastic paraplegia comprises a wide and heterogeneous group of inherited neurodegenerative and neurodevelopmental disorders resulting from primary retrograde dysfunction of the long descending fibers of the corticospinal tract. Although spastic paraparesis and urinary dysfunction represent the most common clinical presentation, a complex group of different neurological and systemic compromise has been recognized recently and a growing number of new genetic subtypes were described in the last decade. Clinical characterization of individual and familial history represents the main step during diagnostic workup; however, frequently, few and unspecific data allows a low rate of definite diagnosis based solely in clinical and neuroimaging basis. Likewise, a wide group of neurological acquired and inherited disorders should be included in the differential diagnosis and properly excluded after a complete laboratorial, neuroimaging, and genetic evaluation. The aim of this review article is to provide an extensive overview regarding the main clinical and genetic features of the classical and recently described subtypes of hereditary spastic paraplegia (HSP).

  13. 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....

  14. [Asymptomatic classical hereditary xanthinuria type 1].

    Science.gov (United States)

    Yakubov, Renata; Nir, Vered; Kassem, Eiass; Klein-Kremer, Adi

    2012-06-01

    We report on a girl who was diagnosed with classical hereditary xanthinuria due to an incidental finding of extremely low Levels of uric acid in the blood. The girl is compLetely asymptomatic. Hereditary xanthinuria is a rare autosomal recessive disease that usually causes early urolithiasis but may cause rheumatoid arthritis-like disease and even be associated with defects in the formation of bone, hair and teeth. In Israel it has mostly been described in patients of Bedouin origin. Throughout the world, only about 150 cases have been described; about two thirds of these patients were asymptomatic. Since the clinical presentation and age of symptom appearance are diverse, the case raises questions as to the required follow-up of these patients and as to whether a low oxalate diet should be initiated.

  15. [Three cases of hereditary xanthinuria: review of the literature (author's transl)].

    Science.gov (United States)

    Temperville, B; Godin, M; Dubois, D; Fillastre, J P

    Xanthinuria is a rare hereditary disorder characterized by a gross deficiency of the enzyme xanthine oxydase resulting in hypouricemia, hypouricosuria and increased serum and urinary oxypurines. Three patients with this disease are presented and the pertinent literature is reviewed. We have demonstrated in one subject the absence of xanthine oxydase activity in a renal fragment. Genetic studies were performed but we do not find any relation between this deficiency of enzyme xanthine oxydase and HLA, Pl, Gm groups.

  16. Alteration of the erythrocyte membrane skeletal ultrastructure in hereditary spherocytosis, hereditary elliptocytosis, and pyropoikilocytosis.

    Science.gov (United States)

    Liu, S C; Derick, L H; Agre, P; Palek, J

    1990-07-01

    The membrane skeleton of normal erythrocytes is largely organized into a hexagonal lattice of junctional complexes (JC) crosslinked by spectrin tetramers, and occasional double tetramers and hexamers. To explore possible skeletal alterations in hereditary spherocytosis (HS), elliptocytosis (HE), and pyropoikilocytosis (HPP), we have studied the ultrastructure of the spread membrane skeletons from a subpopulation of HS patients with a partial spectrin deficiency ranging from 43% to 86% of normal levels, and in patients with HPP who, in addition to a mild spectrin deficiency, also carried a mutant spectrin that was dysfunctional, thus reducing the ability of spectrin dimers to assemble into tetramers. Membrane skeletons derived from Triton-treated erythrocyte ghosts were examined by negative staining electron microscopy. HS membrane skeletons contained structural elements, consisting of JC and spectrin filaments similar to the normal skeleton. However, less spectrin filaments interconnected the JC, and the decrease of spectrin filaments attached to JC appeared to correlate with the severity of spectrin deficiency. Only in severe HS associated with severe spectrin deficiency was the loss of spectrin sufficient enough to disrupt the overall skeletal architecture. In contrast, membrane skeletons prepared from red blood cells (RBCs) of subjects with HPP were strikingly different from HS RBCs with a comparable degree of spectrin deficiency. Although HPP RBCs were only mildly deficient in spectrin, their skeletal lattice was grossly disrupted, in contrast to only mild ultrastructural abnormalities of HS membrane skeletons with a nearly identical degree of spectrin deficiency. Skeletons from patients with common mild HE or asymptomatic carriers, carrying the mutant spectrin but having normal spectrin content, exhibited a moderate disruption of the skeletal lattice. We propose that the above differences in skeletal ultrastructure may underlie differences in the biomechanical

  17. HEREDITARY FRUCTOSE INTOLERANCE – CASE REPORT

    OpenAIRE

    Jernej Brecelj; Gordana Logar-Car; Henrik Peče

    2002-01-01

    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 inf...

  18. Nuclear matrix proteins and hereditary diseases.

    Science.gov (United States)

    Sjakste, N; Sjakste, T

    2005-03-01

    The review summarizes literature data on alterations of structure or expression of different nuclear matrix proteins in hereditary syndromes. From the point of view of involvement of nuclear matrix proteins in etiology and pathogenesis of the disease hereditary pathologies can be classified in pathologies with pathogenesis associated with defects of nuclear matrix proteins and pathologies associated to changes of the nuclear matrix protein spectrum. The first group includes laminopathies, hereditary diseases with abnormal nuclear-matrix associated proteins and triplet extension diseases associated with accumulation of abnormal proteins in the nuclear matrix. Laminopathies are hereditary diseases coupled to structural defects of the nuclear lamina. These diseases include Emery-Dreifuss muscular dystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy (DCM) with conduction system disease, familial partial lipodystrophy (FPLD), autosomal recessive axonal neuropathy (Charcot-Marie-Tooth disorder type 2, CMT2), mandibuloacral dysplasia (MAD), Hutchison Gilford Progeria syndrome (HGS), Greenberg Skeletal Dysplasia, and Pelger-Huet anomaly (PHA). Most of them are due to mutations in the lamin A/C gene, one - to mutations in emerin gene, some are associated with mutations in Lamin B receptor gene. In Werner's, Bloom's, Cockayne's syndromes, Fanconi anemia, multiple carboxylase deficiency mutations in nuclear matrix protein or enzyme gene lead to deficient DNA repair, abnormal regulation of cell growth and differentiation or other specific metabolic functions. Proteins with a long polyglutamic tract synthesized in the cells of patients with dentato-rubral and pallido-luysian atrophy, myotonic dystrophy and Huntington disease interfere with transcription on the nuclear matrix. Down's syndrome is a representative of the group of diseases with altered nuclear matrix protein spectrum.

  19. [Hereditary xanthinuria. A clinical case report].

    Science.gov (United States)

    Pessano, B; Davì, S; La Brocca, A; Leone, L

    1989-05-01

    A case of hereditary xanthinuria in a 68-year-old man with congestive heart failure and alcoholic liver disease is presented. Urolithiasis and muscular symptoms were absent, and the metabolic error was revealed by hypouricemia, hypouricosuria and excess of xanthine and hypoxanthine excretion in urine. Xanthine oxidase (EC 1.2.3.2) activity in liver tissue was absent, confirming the diagnosis of xanthinuria.

  20. Disease: H00106 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available : C1 inhibitor deficiency (hereditary angioedema); C4 binding protein alpha deficiency; C4 binding protein b... subcutaneous and submucosal layers, identified as angioedema (hereditary or acquired). Genetic deficiency o

  1. Hereditary cerebral small vessel disease and stroke.

    Science.gov (United States)

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

    2017-04-01

    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 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 disturbances. Some also present with extra-cerebral manifestations such as microangiopathy of the eyes and kidneys. Many present with clinically recognizable syndromes. Investigations include a thorough family medical history, medical history, neurological examination, neuroimaging, often supplemented by specific examinations e.g of the of vision, retinal changes, as well as kidney and heart function. However molecular genetic analysis is the final gold standard of diagnosis. There are increasing numbers of reports on new monogenic syndromes causing cerebral small vessel disease. Genetic counseling is important. Enzyme replacement therapy is possible in Fabry disease, but treatment options remain overall very limited. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. 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

  3. 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.

  4. Decreased xanthine oxidase activities and increased urinary oxypurines in heterozygotes for hereditary xanthinuria.

    Science.gov (United States)

    Kawachi, M; Kono, N; Mineo, I; Yamada, Y; Tarui, S

    1990-04-30

    Two brothers with hereditary xanthinuria (xanthine oxidase deficiency) and several members of their family were studied. In both subjects, plasma and urinary concentrations of uric acid were low whereas xanthine and hypoxanthine concentrations were markedly elevated. Xanthine oxidase activity was virtually absent in the patients' duodenal mucosa, a finding that established the diagnosis of hereditary xanthinuria. In their parents (obligate heterozygotes), the duodenal xanthine oxidase activity was about 50% of that in control subjects (father 9.3 and mother 12.8 mU/g tissue compared with 21.3 +/- 5.0 mU/g tissue, mean +/- SD). The residual xanthine oxidase from the parents exhibited normal kinetics with respect to hypoxanthine. The parents' urinary xanthine and hypoxanthine concentrations were significantly greater than those of control subjects, while their plasma concentrations of oxypurines were normal. Similar findings were observed in at least 6 other relatives, a finding that suggested that they were heterozygotes. This study suggests that obligate hereditary xanthinuria heterozygotes have only 50% of the xanthine oxidase activity of controls; this deficiency results in a partial metabolic blockage at this enzymatic step in heterozygotes.

  5. Hereditary Risk Evaluation for Borderline Ovarian Tumors Based on Immunohistochemistry

    OpenAIRE

    Park, Jung Min; Kim, Min Kyu

    2014-01-01

    Objectives Borderline ovarian tumors (BOT) are premalignant lesions. Approximately 10% of all epithelial ovarian cancers are known to be hereditary with hereditary breast and ovarian cancer (HBOC) accounting for approximately 90% of cases; the remaining 10% are attributable to Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC). The aim of our study is to estimate this risk based on screening immunohistochemistry (IHC). Methods Thirty-four patients diagnosed with B...

  6. Genetic and phenotypic characterization of complex hereditary spastic paraplegia

    National Research Council Canada - National Science Library

    Kara, Eleanna; Tucci, Arianna; Manzoni, Claudia; Lynch, David S; Elpidorou, Marilena; Bettencourt, Conceicao; Chelban, Viorica; Manole, Andreea; Hamed, Sherifa A; Haridy, Nourelhoda A; Federoff, Monica; Preza, Elisavet; Hughes, Deborah; Pittman, Alan; Jaunmuktane, Zane; Brandner, Sebastian; Xiromerisiou, Georgia; Wiethoff, Sarah; Schottlaender, Lucia; Proukakis, Christos; Morris, Huw; Warner, Tom; Bhatia, Kailash P; Korlipara, L V Prasad; Singleton, Andrew B; Hardy, John; Wood, Nicholas W; Lewis, Patrick A; Houlden, Henry

    2016-01-01

    The hereditary spastic paraplegias are a heterogeneous group of degenerative disorders that are clinically classified as either pure with predominant lower limb spasticity, or complex where spastic...

  7. HEREDITARY COLORECTAL CANCER REGISTRY: A CLEVELAND CLINIC FOUNDATION EXPERIENCE

    Directory of Open Access Journals (Sweden)

    J Church, MBCHB

    2017-07-01

    SUMMARY: the Cleveland Clinic approach to hereditary colorectal cancer is described. This is multidisciplinary, involving several specialties and both genetic counseling and mental health services within the registry.

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

    National Research Council Canada - National Science Library

    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...

  9. Antiretroviral therapy-induced Leber's hereditary optic neuropathy

    National Research Council Canada - National Science Library

    Moodley, A; Bhola, S; Omar, F; Mogambery, J

    2014-01-01

    .... Individuals with the mutation for Leber's hereditary optic neuropathy (LHON), a mitochondrial disorder, are usually asymptomatic but develop visual loss when exposed to external triggers such as smoking...

  10. Human parvovirus infection: rheumatic manifestations, angioedema, C1 esterase inhibitor deficiency, ANA positivity, and possible onset of systemic lupus erythematosus.

    Science.gov (United States)

    Fawaz-Estrup, F

    1996-07-01

    To investigate the clinical and serological characteristics of parvovirus infection. during 1993-4, 9 adult patients presented with polyarthralgias/polyarthritis. Clinical evaluation and serological studies of antinuclear antibodies, rheumatoid factor (RF), IgM and IgG antibodies to human parvovirus were done in all patients. Other serologies including anti-DNA, serum complement, and C1 esterase inhibitor levels were obtained in some patients. All 9 patients had polyarthralgias/polyarthritis, serological evidence of parvovirus B19 IgM and IgG antibodies, and normal sedimentation rate. All patients were seronegative for RF. Four women had positive ANA titers. In 2 of them the ANA positivity was transient. One developed systemic lupus erythematosus (SLE). Three women had angioedema of the face and tongue; one had transient C1 esterase inhibitor deficiency and another a transient decrease in C4 levels. Parvovirus may be implicated in the development of SLE as well as other chronic arthropathies. This is the first reported case of angioedema and decreased C1 esterase inhibitor levels associated with parvovirus infection.

  11. Angiotensin-converting enzyme (ACE) inhibitor-associated angioedema of the stomach and small intestine: a case report.

    Science.gov (United States)

    Shahzad, Ghulamullah; Korsten, Mark A; Blatt, Charles; Motwani, Pooja

    2006-12-01

    This is a case report on a 45-year old African-American female with newly diagnosed hypertension, who was started on a combination pill of amlodipine/benazapril 10/5 mg. The very next day, she presented at the emergency room (ER) with abdominal pain, nausea and vomiting. Physical exam, complete metabolic panel, and hemogram were in the normal range. She was discharged from the ER after a few hours of treatment with fluid and analgesics. However, she returned to the ER the next day with the same complaints. This time the physical exam was significant for a distended abdomen with dullness to percussion. CT scan of the abdomen revealed markedly thickened antrum of the stomach, duodenum and jejunum, along with fluid in the abdominal and pelvic cavity. Angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema was suspected, and anti-hypertensive medications were discontinued. Her symptoms improved within the next 24 hours, and repeat CT after 72 hours revealed marked improvement in stomach and small bowel thickening and resolution of ascites. The recognition of angiotensin-converting enzyme (ACE) and angiotensin receptor blocker (ARB) intestinal angioedema constitutes a challenge to primary care physicians, internists, emergency room personal and surgeons.

  12. Monocyte transferrin-iron uptake in hereditary hemochromatosis

    Energy Technology Data Exchange (ETDEWEB)

    Sizemore, D.J.; Bassett, M.L.

    1984-05-01

    Transferrin-iron uptake by peripheral blood monocytes was studied in vitro to test the hypothesis that the relative paucity of mononuclear phagocyte iron loading in hereditary hemochromatosis results from a defect in uptake of iron from transferrin. Monocytes from nine control subjects and 17 patients with hemochromatosis were cultured in the presence of 59Fe-labelled human transferrin. There was no difference in 59Fe uptake between monocytes from control subjects and monocytes from patients with hemochromatosis who had been treated by phlebotomy and who had normal body iron stores. However, 59Fe uptake by monocytes from iron-loaded patients with hemochromatosis was significantly reduced compared with either control subjects or treated hemochromatosis patients. It is likely that this was a secondary effect of iron loading since iron uptake by monocytes from treated hemochromatosis patients was normal. Assuming that monocytes in culture reflect mononuclear phagocyte iron metabolism in vivo, this study suggests that the relative paucity of mononuclear phagocyte iron loading in hemochromatosis is not related to an abnormality in transferrin-iron uptake by these cells.

  13. [Genetic testing in hereditary spastic paraplegia].

    Science.gov (United States)

    Hadzsiev, Kinga; Balikó, László; Komlósi, Katalin; Lőcsei-Fekete, Anett; Csábi, Györgyi; Bene, Judit; Kisfali, Péter; Melegh, Béla

    2015-01-18

    Hereditary spastic paraplegia is the overall term for clinically and genetically diverse disorders characterized with progressive and variable severe lower extremity spasticity. The most common causes of autosomal dominantly inherited hereditary spastic paraplegias are different mutations of the spastin gene with variable incidence in different ethnic groups, ranging between 15-40%. Mutations in the spastin gene lead to loss of spastins function, causing progressive neuronal failure, which results in axon degeneration finally. The molecular testing of spastin gene is available in the institution of the authors since January, 2014. The experience gained with the examination of the first eleven patients is described in this article. After polymerase chain reaction, Sanger sequencing was performed to examine the 17 exons of the spastin gene. Multiplex ligation-dependent probe amplification was performed to detect greater rearrangements in the spastin gene. Eight of the patients were examined in the genetic counseling clinic of the authors and after detailed phenotype assessment spastin gene testing was obtained. The other three patients were referred to the laboratory from different outpatient clinics. Out of the 11 examined patients, four different pathogenic mutations were found in 5 patients. The first Hungarian data, gained with the examination of spastin gene are presented in this article. The five patients, in whom mutations were detected, represent 45.5% of all tested patients with hereditary spastic paraplegia, which is similar to those published in the international literature. Molecular testing and subsequent detailed genotype-phenotype correlations of the Hungarian patients may serve valuable new information about the disease, which later on may influence our therapeutic possibilities and decisions.

  14. Hereditary Colorectal Cancer (CRC Program in Latvia

    Directory of Open Access Journals (Sweden)

    Irmejs Arvids

    2003-12-01

    Full Text Available Abstract Introduction The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35% pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC and 15 cases (1.73% were suspected of HNPCC. In 69 cases (8% with a cancer family aggregation (CFA were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.

  15. Genetic heterogeneity in hereditary haemorrhagic telangiectasia.

    Science.gov (United States)

    Porteous, M E; Curtis, A; Williams, O; Marchuk, D; Bhattacharya, S S; Burn, J

    1994-01-01

    A locus causing hereditary haemorrhagic telangiectasia (HHT) has recently been mapped to 9q34 in four families and designated HHT1. In this paper, the results of a linkage study showing genetic heterogeneity in four families in whom HHT is segregating are reported. All the previously reported 9q34 linked families contain at least one affected member with a symptomatic pulmonary arteriovenous malformation. We postulate that clinical heterogeneity may also be a feature of HHT with a significantly higher predisposition to symptomatic PAVMs associated with the HHT1 linked families. PMID:7891373

  16. Asymptomatic hereditary xanthinuria: a case report.

    Science.gov (United States)

    Nagae, A; Murakami, E; Hiwada, K; Sato, Y; Kawachi, M; Kono, N

    1990-01-01

    A 22-year-old man with hereditary xanthinuria is reported. A biochemical study of the patient showed elevated serum levels of xanthine and hypoxanthine with concomitant increases in urinary excretion of xanthine and hypoxanthine. The xanthine oxidase activity in the duodenal mucosa of the patient was about 1.5% of normal value. Urinary excretion of xanthine and hypoxanthine of his parents and his eldest brother were significantly higher than the corresponding normal values, but the values were much less than those of the patient. The results suggested that the patient was homozygote, and his parents and his eldest brother were heterozygotes.

  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. 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....

  19. Learning Hereditary and Reductive Prolog Programs from Entailment

    Science.gov (United States)

    Hussain, Shahid; Rao, M. R. K. Krishna

    In this paper we study exact learning of Prolog programs from entailment and present an algorithm to learn two rich classes of Prolog programs namely hereditary and reductive Prolog programs. These classes contain standard Prolog programs with and without recursion like append, merge, split, delete, member, prefix, suffix, length, add, etc. Additionally our algorithm learns the hereditary Prolog programs in polynomial time.

  20. Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations

    NARCIS (Netherlands)

    Sijmons, Rolf H.; Hofstra, Robert M. W.

    Inherited mutations of the DNA Mismatch repair genes MLH1, MSH2, MSH6 and PMS2 can result in two hereditary tumor syndromes: the adult-onset autosomal dominant Lynch syndrome, previously referred to as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the childhood-onset autosomal recessive

  1. Methylation profiles of hereditary and sporadic ovarian cancer

    NARCIS (Netherlands)

    Bol, Guus M.; Suijkerbuijk, Karijn P. M.; Bart, Joost; Vooijs, Marc; van der Wall, Elsken; van Diest, Paul J.

    Aims: Tumour suppressor gene silencing through promoter hypermethylation plays an important role in oncogenesis. Carcinogenesis of hereditary cancers usually differs from that of their sporadic counterparts, but methylation has hardly been studied in hereditary ovarian cancer. The aim of this study

  2. 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 cancer...... 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....... (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers...

  3. Genetic profiles distinguish different types of hereditary ovarian cancer

    DEFF Research Database (Denmark)

    Domanska, Katarina; Malander, Susanne; Staaf, Johan

    2010-01-01

    (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers......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 cancer...... 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....

  4. Hereditary ovarian cancer: beyond the usual suspects.

    Science.gov (United States)

    Pennington, Kathryn P; Swisher, Elizabeth M

    2012-02-01

    In the past, hereditary ovarian carcinoma was attributed almost entirely to mutations in BRCA1 and BRCA2, with a much smaller contribution from mutations in DNA mismatch repair genes. Recently, three new ovarian cancer susceptibility genes have been identified: RAD51C, RAD51D, and BRIP1. In addition, germline mutations in women with ovarian carcinoma have been recently identified in many of the previously identified breast cancer genes in the Fanconi anemia (FA)-BRCA pathway. While mutations in genes other than BRCA1 and BRCA2 are each individually rare, together they make up a significant proportion of cases. With at least 16 genes implicated in hereditary ovarian cancer to date, comprehensive testing for ovarian cancer risk will require assessment of many genes. As the cost of genomic sequencing continues to fall, the practice of evaluating cancer susceptibility one gene at a time is rapidly becoming obsolete. New advances in genomic technologies will likely accelerate the discovery of additional cancer susceptibility genes and increase the feasibility of comprehensive evaluation of multiple genes simultaneously at low cost. Improved recognition of inherited risk will identify individuals who are candidates for targeted prevention. In addition, identifying inherited mutations in a variety of FA-BRCA pathway genes may aid in identifying individuals who will selectively benefit from PARP inhibitors. Copyright © 2011. Published by Elsevier Inc.

  5. Genetics of hereditary head and neck paragangliomas.

    Science.gov (United States)

    Boedeker, Carsten C; Hensen, Erik F; Neumann, Hartmut P H; Maier, Wolfgang; van Nederveen, Francien H; Suárez, Carlos; Kunst, Henricus P; Rodrigo, Juan P; Takes, Robert P; Pellitteri, Phillip K; Rinaldo, Alessandra; Ferlito, Alfio

    2014-06-01

    The purpose of this study was to give an overview on hereditary syndromes associated with head and neck paragangliomas (HNPGs). Our methods were the review and discussion of the pertinent literature. About one third of all patients with HNPGs are carriers of germline mutations. Hereditary HNPGs have been described in association with mutations of 10 different genes. Mutations of the genes succinate dehydrogenase subunit D (SDHD), succinate dehydrogenase complex assembly factor 2 gene (SDHAF2), succinate dehydrogenase subunit C (SDHC), and succinate dehydrogenase subunit B (SDHB) are the cause of paraganglioma syndromes (PGLs) 1, 2, 3, and 4. Succinate dehydrogenase subunit A (SDHA), von Hippel-Lindau (VHL), and transmembrane protein 127 (TMEM127) gene mutations also harbor the risk for HNPG development. HNPGs in patients with rearranged during transfection (RET), neurofibromatosis type 1 (NF1), and MYC-associated factor X (MAX) gene mutations have been described very infrequently. All patients with HNPGs should be offered a molecular genetic screening. This screening may usually be restricted to mutations of the genes SDHD, SDHB, and SDHC. Certain clinical parameters can help to set up the order in which those genes should be tested. © 2013 Wiley Periodicals, Inc.

  6. Recommendations regarding splenectomy in hereditary hemolytic anemias.

    Science.gov (United States)

    Iolascon, Achille; Andolfo, Immacolata; Barcellini, Wilma; Corcione, Francesco; Garçon, Loïc; De Franceschi, Lucia; Pignata, Claudio; Graziadei, Giovanna; Pospisilova, Dagmar; Rees, David C; de Montalembert, Mariane; Rivella, Stefano; Gambale, Antonella; Russo, Roberta; Ribeiro, Leticia; Vives-Corrons, Jules; Martinez, Patricia Aguilar; Kattamis, Antonis; Gulbis, Beatrice; Cappellini, Maria Domenica; Roberts, Irene; Tamary, Hannah

    2017-08-01

    Hereditary hemolytic anemias are a group of disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and hemoglobinopathies. As damaged red blood cells passing through the red pulp of the spleen are removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications. In light of the priorities identified by the European Hematology Association Roadmap we generated specific recommendations for each disorder, except thalassemia syndromes for which there are other, recent guidelines. Our recommendations are intended to enable clinicians to achieve better informed decisions on disease management by splenectomy, on the type of splenectomy and the possible consequences. As no randomized clinical trials, case control or cohort studies regarding splenectomy in these disorders were found in the literature, recommendations for each disease were based on expert opinion and were subsequently critically revised and modified by the Splenectomy in Rare Anemias Study Group, which includes hematologists caring for both adults and children. Copyright© 2017 Ferrata Storti Foundation.

  7. 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.

  8. Recommendations regarding splenectomy in hereditary hemolytic anemias

    Science.gov (United States)

    Iolascon, Achille; Andolfo, Immacolata; Barcellini, Wilma; Corcione, Francesco; Garçon, Loïc; De Franceschi, Lucia; Pignata, Claudio; Graziadei, Giovanna; Pospisilova, Dagmar; Rees, David C.; de Montalembert, Mariane; Rivella, Stefano; Gambale, Antonella; Russo, Roberta; Ribeiro, Leticia; Vives-Corrons, Jules; Martinez, Patricia Aguilar; Kattamis, Antonis; Gulbis, Beatrice; Cappellini, Maria Domenica; Roberts, Irene; Tamary, Hannah

    2017-01-01

    Hereditary hemolytic anemias are a group of disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and hemoglobinopathies. As damaged red blood cells passing through the red pulp of the spleen are removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications. In light of the priorities identified by the European Hematology Association Roadmap we generated specific recommendations for each disorder, except thalassemia syndromes for which there are other, recent guidelines. Our recommendations are intended to enable clinicians to achieve better informed decisions on disease management by splenectomy, on the type of splenectomy and the possible consequences. As no randomized clinical trials, case control or cohort studies regarding splenectomy in these disorders were found in the literature, recommendations for each disease were based on expert opinion and were subsequently critically revised and modified by the Splenectomy in Rare Anemias Study Group, which includes hematologists caring for both adults and children. PMID:28550188

  9. 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

  10. Hereditary xanthinuria: report of two cases.

    Science.gov (United States)

    Chu, T S

    1993-05-01

    Hereditary xanthinuria is a rare disorder characterized by the replacement of uric acid by xanthine and hypoxanthine in urine. Two cases of classic hereditary xanthinuria in Taiwan are herein reported. Case 1: a 30-year-old woman was by chance found to have hypouricemia. Urine and plasma purines were checked through the use of high performance liquid chromatography. Urine excretion of uric acid was 0.029 mumol (0.005 mg)/mg creatinine (30 mumol/24 hr); xanthine 1.9 mumol/mg creatinine (1935 mumol/24 hr); and hypoxanthine 0.58 mumol/mg creatinine (587 mumol/24 hr). Plasma xanthine was 9.3 mumol/L; hypoxanthine 5.8 mumol/L; and uric acid 0.5 mumol/L (0.001 mg/dL). Case 2: a brother of case 1 had a previous history of urolithiasis. Urine excretion of uric acid was 0.15 mumol (0.025 mg)/mg creatinine (189 mumol/24 hr); xanthine 1.3 mumol/mg creatinine (1620 mumol/24 hr); and hypoxanthine 0.22 mumol/mg creatinine (276 mumol/24 hr).

  11. Aqueous humor ferritin in hereditary hyperferritinemia cataract syndrome.

    Science.gov (United States)

    Lenzhofer, Markus; Schroedl, Falk; Trost, Andrea; Kaser-Eichberger, Alexandra; Wiedemann, Helmut; Strohmaier, Clemens; Hohensinn, Melchior; Strasser, Michael; Muckenthaler, Martina U; Grabner, Guenther; Aigner, Elmar; Reitsamer, Herbert A

    2015-04-01

    Hereditary hyperferritinemia cataract syndrome (HHCS) is a rare autosomal dominant hereditary disease, characterized by hyperferritinemia but with absence of body iron excess and early onset of bilateral cataracts. Although 5- to 20-fold increased serum ferritin concentrations have been reported in HHCS patients, data of ferritin levels in aqueous humor have not been obtained. We therefore aimed to investigate the ferritin levels in aqueous humor and serum and further present histological and ultrastructural data of the lens. During cataract extraction and intraocular lens implantation, aqueous humor and lens aspirate of a 37-year-old HHCS patient were obtained from both eyes. Ferritin levels in serum and aqueous humor were quantitatively analyzed via immunoassays in the HHCS patient and healthy control subjects (n = 6). Lens aspirate in HHCS was analyzed histologically and at the ultrastructural level. Further, genetic mutation screening by polymerase chain reaction and DNA sequencing in blood was performed. Serum ferritin levels in the control group were 142.2 ± 38.7 μg/L, whereas in the HHCS patient, this parameter was excessively increased (1086 μg/L). Analysis of ferritin in aqueous humor revealed 6.4 ± 3.8 μg/L in normal control subjects and 146.3 μg/L (OD) and 160.4 μg/L (OS) in the HHCS patient. DNA analysis detected a C>A mutation on position +18, a T>G mutation on position +22, a T>C mutation on position +24, and a T>G polymorphism on position +26 in the iron-responsive element of the light-chain ferritin (L-ferritin) gene. In the HHCS patient, a 23-fold (OD) to 25-fold (OS) increased aqueous humor ferritin level was detected. Therefore, the formation of bilateral cataract in HHCS is most likely a result of elevated aqueous humor ferritin. In addition, a novel mutation in this rare disease in the iron-responsive element of L-ferritin gene is reported.

  12. Effectiveness of preoperative plasmapheresis in a pregnancy complicated by hyperthyroidism and anti-thyroid drug-associated angioedema.

    Science.gov (United States)

    Bilir, B Ekiz; Atile, N Soysal; Kirkizlar, O; Kömürcü, Y; Akpinar, S; Sezer, A; Demir, M; Hekimoğlu, S

    2013-05-01

    Hyperthyroidism is not a rare entity in pregnancy and 85% of these cases attributed to Graves' disease (GD). There is no therapeutic modality for GD considered as totally safe in pregnancy. Fetal and neonatal risks of maternal hyperthyroid disease are related to the hyperthyroidism itself and/or to the medical treatment of the disease. There are no data supporting an association between congenital anomalies in the fetus and propylthiouracil (PTU). Hepatotoxicity, cytopenias--especially agranulocytosis and quite rarely, angioedema, may be seen as side effects of PTU. In this case report, we examine an instance of Graves' hyperthyroidism diagnosed during pregnancy. In this case, a serious side effect during anti-thyroid drug usage was encountered, eventually resulting in surgery in the second trimester. This intervention was assisted by the use of plasmapheresis to obtain rapid normalization of serum thyroid hormone levels.

  13. Avoidance of nonsteroidal anti-inflammatory drugs after negative provocation tests in urticaria/angioedema reactions: Real-world experience.

    Science.gov (United States)

    Bommarito, Luisa; Zisa, Giuliana; Riccobono, Francesca; Villa, Elisa; D'Antonio, Cristian; Calamari, Ambra M; Poppa, Mariangela; Moschella, Adele; Di Pietrantonj, Carlo; Galimberti, Maurizio

    2014-01-01

    Drug provocation tests (DPTs) are the gold standard in diagnosing nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity; however, only few data about follow-up of patients with negative DPTs are actually available. The aim of this study was to assess patients' behavior in taking NSAIDs again and to evaluate NSAID tolerability after negative allergological workup. This is a follow-up study involving patients evaluated for history of cutaneous reactions (urticaria and or angioedema) after NSAID intake and with negative DPTs with the suspected NSAID. Patients were asked during a phone interview about the intake of NSAIDs, tolerance, or reasons of avoidance. The negative predictive value (NPV) of NSAIDs DPTs was calculated. One hundred eleven of 142 patients were successfully contacted; 46/111 (41.44%) took the same NSAID previously tested with two adverse reactions reported (4.34%). Fifty-three of 111 (47.74%) patients did not take the same NSAID, but 34 of them took at least another strong cyclooxygenase (COX) 1 inhibitor, with 1 adverse reaction (2.94%) and 19 of them took only weak COX-1 inhibitors. Twelve of 111 patients (10.8%) did not take any NSAID. Reasons for drug avoidance were mainly fear of reactions (70.8%) and no need (29.2%). NPV, overall, was 96.97% (95% confidence interval, 91-99%). Although NSAID hypersensitivity diagnosis was ruled out by oral provocation test, the majority of patients with a history of urticaria/angioedema avoided the intake of the tested NSAIDs for fear of new reactions, particularly when strong COX-1 inhibitor NSAIDs were involved. The high NPV value of DPT resulting from this study should reassure NSAID intake.

  14. Oral drug challenges in non-steroidal anti-inflammatory drug-induced urticaria, angioedema and anaphylaxis.

    Science.gov (United States)

    Chaudhry, T; Hissaria, P; Wiese, M; Heddle, R; Kette, F; Smith, W B

    2012-06-01

    Urticaria, angioedema and anaphylaxis are common adverse reactions to non-steroidal anti-inflammatory drugs (NSAIDs). To investigate the clinical characteristics of NSAID-induced acute hypersensitivity reactions with structured oral drug challenges. Patients with NSAID-induced urticaria, angioedema or anaphylaxis were challenged with either the homologous NSAID to confirm diagnosis or a heterologous NSAID to investigate cross-reactivity. Data were analysed retrospectively and supplemented by a telephone questionnaire. Sixty-eight patients (mean age 48.3, 53 females) reported a total of 75 instances of NSAID-induced reactions of which 64% were purely cutaneous and 36% were systemic anaphylaxis. Ibuprofen was the most frequent cause of reactions (35%), however, diclofenac was the most frequent cause of anaphylaxis (48%). Seventeen out of 40 (43%) homologous NSAID challenges were positive; presentation with anaphylaxis or reaction to diclofenac predicted a positive challenge. Only 7 of 28 (25%) of heterologous NSAID challenges were positive. Structured challenges enabled us to identify 23 (34%) patients with selective reactivity to a single NSAID, 19 (28%) patients with cross-reactivity to multiple NSAIDs and 23 (34%) patients in whom NSAID hypersensitivity was not reproduced. Selective reactors presented most often with anaphylaxis and some had a background of beta-lactam antibiotic allergy. Cross-reactive patients often had a background of chronic urticaria and presented with milder reactions. In the absence of a reliable in vitro test, structured drug challenges allow identification of selective and cross-reactive NSAID hypersensitivity syndromes. NSAID-induced anaphylaxis is often associated with selective hypersensitivity and patients may not need to avoid other NSAIDs. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

  15. Gait evolution in a family with hereditary spastic paraplegia.

    Science.gov (United States)

    Armand, Stéphane; Turcot, Katia; Bonnefoy-Mazure, Alice; Lascombes, Pierre; De Coulon, Geraldo

    2015-01-01

    The degree of disability in patients with hereditary spastic paraplegia has been reported variable even in members of the same family (same gene mutation). Moreover, it has been established that patients with hereditary spastic paraplegia should be treated differently from cerebral palsy patients due to the progressive nature of this disease. However, the gait evolution of hereditary spastic paraplegia showing onset symptoms at an early age has been described as stable. Therefore, this study aims to evaluate the walking ability and the influence of treatments on gait evolution in a family with hereditary spastic paraplegia. Clinical gait analyses were performed in six hereditary spastic paraplegia patients from the same family with a follow-up of 4-15 years. Based on the gait deviation index, results showed a large variation of walking ability in these patients and no statistical difference between the first and last examination. In fact, three patients have improved their gait (from childhood to adolescence) whereas three patients worsened their gait. Gait alterations in a family with hereditary spastic paraplegia are heterogeneous. Gait evolution in hereditary spastic paraplegia with early symptoms had a tendency to improve gait until adolescence with adapted treatments and to decline in the adulthood. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  16. Committee opinion no. 634: Hereditary cancer syndromes and risk assessment.

    Science.gov (United States)

    2015-06-01

    A hereditary cancer syndrome is a genetic predisposition to certain types of cancer, often with onset at an early age, caused by inherited mutations in one or more genes. Cases of cancer commonly encountered by obstetrician-gynecologists or other obstetric-gynecologic providers--such as breast cancer, ovarian cancer, and endometrial cancer--are features of specific hereditary cancer syndromes. The most common hereditary cancer syndromes related to gynecologic cancer include hereditary breast and ovarian cancer syndrome, Lynch syndrome, Li-Fraumeni syndrome, Cowden syndrome, and Peutz-Jeghers syndrome. A hereditary cancer risk assessment is the key to identifying patients and families who may be at increased risk of developing certain types of cancer. Screening should include, at minimum, a personal cancer history and a first- and second-degree relative cancer history that includes a description of the type of primary cancer, the age of onset, and the lineage (paternal versus maternal) of the family member. In addition, a patient's ethnic background can influence her genetic risk. If a hereditary cancer risk assessment suggests an increased risk of a hereditary cancer syndrome, referral to a specialist in cancer genetics or a health care provider with expertise in genetics is recommended for expanded gathering of family history information, risk assessment, education, and counseling, which may lead to genetic testing.

  17. Alteration of ornithine metabolism leads to dominant and recessive hereditary spastic paraplegia.

    Science.gov (United States)

    Coutelier, Marie; Goizet, Cyril; Durr, Alexandra; Habarou, Florence; Morais, Sara; Dionne-Laporte, Alexandre; Tao, Feifei; Konop, Juliette; Stoll, Marion; Charles, Perrine; Jacoupy, Maxime; Matusiak, Raphaël; Alonso, Isabel; Tallaksen, Chantal; Mairey, Mathilde; Kennerson, Marina; Gaussen, Marion; Schule, Rebecca; Janin, Maxime; Morice-Picard, Fanny; Durand, Christelle M; Depienne, Christel; Calvas, Patrick; Coutinho, Paula; Saudubray, Jean-Marie; Rouleau, Guy; Brice, Alexis; Nicholson, Garth; Darios, Frédéric; Loureiro, José L; Zuchner, Stephan; Ottolenghi, Chris; Mochel, Fanny; Stevanin, Giovanni

    2015-08-01

    Hereditary spastic paraplegias are heterogeneous neurological disorders characterized by a pyramidal syndrome with symptoms predominantly affecting the lower limbs. Some limited pyramidal involvement also occurs in patients with an autosomal recessive neurocutaneous syndrome due to ALDH18A1 mutations. ALDH18A1 encodes delta-1-pyrroline-5-carboxylate synthase (P5CS), an enzyme that catalyses the first and common step of proline and ornithine biosynthesis from glutamate. Through exome sequencing and candidate gene screening, we report two families with autosomal recessive transmission of ALDH18A1 mutations, and predominant complex hereditary spastic paraplegia with marked cognitive impairment, without any cutaneous abnormality. More interestingly, we also identified monoallelic ALDH18A1 mutations segregating in three independent families with autosomal dominant pure or complex hereditary spastic paraplegia, as well as in two sporadic patients. Low levels of plasma ornithine, citrulline, arginine and proline in four individuals from two families suggested P5CS deficiency. Glutamine loading tests in two fibroblast cultures from two related affected subjects confirmed a metabolic block at the level of P5CS in vivo. Besides expanding the clinical spectrum of ALDH18A1-related pathology, we describe mutations segregating in an autosomal dominant pattern. The latter are associated with a potential trait biomarker; we therefore suggest including amino acid chromatography in the clinico-genetic work-up of hereditary spastic paraplegia, particularly in dominant cases, as the associated phenotype is not distinct from other causative genes. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Genes and SNPs associated with non-hereditary and hereditary colorectal cancer.

    Science.gov (United States)

    Nassiri, Mohammadreza; Kooshyar, Mohammad Mahdi; Roudbar, Zahra; Mahdavi, Morteza; Doosti, Mohammad

    2013-01-01

    Colorectal cancer is the third most common cancer in both men and women in the world and the second leading cause of cancer-related deaths. The incidence of colorectal cancer has increased in Iran in the past three decades and is now considered as a serious problem for our society. This cancer has two types hereditary and non-hereditary, 80% of cases being the latter. Considering that the relationship between SNPs with diseases is a concern, many researchers believed that they offer valuable markers for identifying genes responsible for susceptibility to common diseases. In some cases, they are direct causes of human disease. One SNP can increase risk of cancer, but when considering the rate of overlap and frequency of DNA repair pathways, it might be expected that SNP alone cannot affect the final result of cancer, although several SNPs together can exert a significant influence. Therefore identification of these SNPs is very important. The most important loci which include mutations are: MLH1, MSH2, PMS2, APC, MUTYH, SMAD7, STK11, XRCC3, DNMT1, MTHFR, Exo1, XRCC1 and VDR. Presence of SNPs in these genes decreases or increases risk of colorectal cancer. In this article we reviewed the Genes and SNPs associated with non-hereditary and hereditary of colorectal cancer that recently were reported from candidate gene y, meta-analysis and GWAS studies. As with other cancers, colorectal cancer is associated with SNPs in gene loci. Generally, by exploring SNPs, it is feasible to predict the risk of developing colorectal cancer and thus establishing proper preventive measures. SNPs of genes associated with colorectal cancer can be used as a marker SNP panel as a potential tool for improving cancer diagnosis and treatment planning.

  19. [The broad phenotypic spectrum of SCA-3: hereditary spastic paraplegia].

    Science.gov (United States)

    Rodríguez-Quiroga, Sergio A; González-Morón, Dolores; Arakaki, Tomoko; Garreto, Nélida; Kauffman, Marcelo A

    2013-01-01

    Machado-Joseph disease (MJD) is the most frequent dominantly inherited spinocerebellar ataxia. A marked phenotypic variability is a characteristic of this disorder that could involve non-cerebellar presentations. Based on several case reports describing pyramidal dysfunction as the main symptom at onset, a clinical form resembling hereditary spastic paraplegia has been proposed. We report here two further cases of MJD patients whose initial clinical presentation suggested hereditary spastic paraplegia, and a summary of the main findings of previously similar published reports. Our findings lent support to the proposal of a MJD subtype distinguished by a marked pyramidal dysfunction at onset, simulating a clinical picture of hereditary spastic paraplegia.

  20. 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.

  1. Molecular aspects of hereditary spastic paraplegia.

    Science.gov (United States)

    Noreau, Anne; Dion, Patrick A; Rouleau, Guy A

    2014-07-01

    Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by progressive lower limbs spasticity and weakness. What was first thought to be a small group of rare Mendelian disorder has now become a large group that includes many complex syndromes. While large families with defined modes of inheritance were used for the initial HSP gene discovery, new sequencing technologies have recently allowed the study of small families, with the identification of many new disease causative genes. These discoveries are slowly leading to a better understanding of the molecular mechanisms underlying HSP with the identification of precise disease pathways. These insights may lead to new therapeutic strategies for what is a group of largely untreatable diseases. This review looks at the key players involved in HSP and where they act in their specific pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. 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....

  3. Genetics of hereditary large vessel diseases.

    Science.gov (United States)

    Morisaki, Takayuki; Morisaki, Hiroko

    2016-01-01

    Recent progress in the study of hereditary large vessel diseases such as Marfan syndrome (MFS) have not only identified responsible genes but also provided better understanding of the pathophysiology and revealed possible new therapeutic targets. Genes identified for these diseases include FBN1, TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3, SKI, EFEMP2, COL3A1, FLNA, ACTA2, MYH11, MYLK and SLC2A10, as well as others. Their dysfunction disrupts the function of transforming growth factor-β (TGF-β) signaling pathways, as well as that of the extracellular matrix and smooth muscle contractile apparatus, resulting in progression of structural damage to large vessels, including aortic aneurysms and dissections. Notably, it has been shown that the TGF-β signaling pathway has a key role in the pathogenesis of MFS and related disorders, which may be important for development of strategies for medical and surgical treatment of thoracic aortic aneurysms and dissections.

  4. Skin deposits in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Blöndal, H; Gudmundsson, G

    1990-01-01

    . 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......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...

  5. [Hereditary ichthyosis: A diagnostic and therapeutic challenge].

    Science.gov (United States)

    Vega Almendra, Nadia; Aranibar Duran, Ligia

    2016-01-01

    Hereditary ichthyoses are a group of genetic disorders of cornification, which are characterised by hyperkeratosis and scaling. The new classification identifies 36 types of ichthyosis, which are subdivided according to their frequency, pattern of inheritance and extracutaneous involvement. The diagnosis is mainly based on clinical features, since genetic studies are not available in our setting. Treatment is symptomatic and management should be performed by a multidisciplinary team. In this article, the diagnostic and therapeutic aspects of different types of ichthyosis are reviewed, taking into account the nomenclature and modifications presented in the new classification. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Leber's Hereditary Optic Neuropathy: A Case Report

    Directory of Open Access Journals (Sweden)

    Chi-Wu Chang

    2003-10-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally inherited mitochondrial disease that primarily affects the optic nerve, causing bilateral vision loss in juveniles and young adults. A 12-year-old boy had complained of blurred vision in both eyes for more than 1 year. His best-corrected visual acuity was 0.08 in the right eye and 0.1 in the left. Ophthalmologic examination showed bilateral optic disc hyperemia and margin blurring, peripapillary telangiectasis, and a relative afferent pupil defect in his right eye. Fluorescein angiography showed no stain or leakage around the optic disc in the late phase. Visual field analysis showed central scotoma in the left eye and a near-total defect in the right. Upon examination of the patient's mitochondrial DNA, a point mutation at nucleotide position 11778 was found, and the diagnosis of LHON was confirmed. Coenzyme Q10 was used to treat the patient.

  7. Pulmonary vascular complications of hereditary haemorrhagic telangiectasia.

    Science.gov (United States)

    Circo, Sebastian; Gossage, James R

    2014-09-01

    The purpose of this study is to present the latest advances and recommendations in the diagnosis and treatment of pulmonary vascular complications associated with hereditary haemorrhagic telangiectasia (HHT): pulmonary arteriovenous malformations (PAVMs), pulmonary arterial hypertension (PAH), pulmonary hypertension associated with high output cardiac failure or liver vascular malformations, haemoptysis, haemothorax and thromboembolic disease. Transthoracic contrast echocardiography has been validated as a screening tool for PAVM in patients with suspected HHT. Advancements in genetic testing support its use in family members at risk as a cost-effective measure. Therapy with bevacizumab in patients with high output cardiac failure and severe liver AVMs showed promising results. PAH tends to be more aggressive in HHT type 2 patients. Patients suffering from this elusive disease should be referred to HHT specialized centres to ensure a standardized and timely approach to diagnosis and management.

  8. Surgical treatment of gastrointestinal hereditary hemorrhagic telangiectasia.

    Science.gov (United States)

    Yen, Min-Hsuan; Chen, Chiung-Nien

    2016-04-01

    A 48-year-old man with a history of gastrointestinal bleeding from Osler-Weber-Rendu disease presented with recurrent hematemesis and tarry stool. He received repeated endoscopic therapy, but profound component therapy was still needed. Because repeated gastrointestinal bleeding was caused by same bleeder, tattoo-assisted laparoscopic gastric wedge resection was carried out. The pathology showed vascular abnormalities that involved gastric mucosal and submucosal layers. After surgery, the blood transfusion for the patient is not seen. Osler-Weber-Rendu is a hereditary disease characterized by vascular abnormalities of the nose, skin, lung, brain, and gastrointestinal tract. Management of gastrointestinal bleeding requires medical treatment first, and there are rare reports of surgical treatment. Our pathology findings showed a transmucosal vessel lesion, which had poor response to endoscopic treatment. Surgical intervention may be considered in the patient with gastrointestinal bleeding refractory to endoscopic therapy.

  9. [Hereditary porphyrias and heme related disorders].

    Science.gov (United States)

    Puy, Hervé; Gouya, Laurent; Deybach, Jean-charles

    2014-06-01

    Hereditary porphyrias comprise a group of eight metabolic disorders of the haem biosynthesis pathway, characterised by acute neurovisceral symptoms and/or skin lesions. Each porphyria is caused by abnormal functioning of a particular enzymatic step, resulting in specific accumulation of heme precursors. Seven porphyrias are due to a partial enzyme deficiency, while a gain-of-function mechanism has recently been identify in a novel porphyria. Acute porphyrias present with severe abdominal pain, nausea, constipation and confusion, and are sometimes complicated by seizures and severe neurological disorders, which may be life-threatening. Cutaneous porphyrias can also be present, with either acute painful photosensitivity or skin fragility and blisters. Rare recessive porphyrias usually manifest in early childhood with either severe chronic neurological symptoms or chronic haemolysis and severe cutaneous photosensitivity. Porphyrias are still under-diagnosed, but recent advances in the pathogenesis and genetics of human porphyrias are leading to better care of these patients and their families.

  10. Mania associated with complicated hereditary spastic paraparesis

    Directory of Open Access Journals (Sweden)

    Raghavendra B Nayak

    2011-01-01

    Full Text Available Hereditary spastic paraparesis (HSP is an inherited group of neurological disorders with progressive lower limb spasticity. HSP can be clinically grouped into pure and complicated forms. Pure HSP is one without any associated neurological/psychiatric comorbidity. Depression is the most common psychiatric comorbidity. Presence of mania or bipolar affective illness with HSP is a rare phenomenon. We report a case of a 17-year-old boy who presented with classical features of HSP with complaints of excessive happiness, irritability, increased self-esteem and decreased sleep since 1 month. The patient also had complex partial seizure ever since he had features of HSP. The patient′s father and younger sister suffer from pure HSP. The patient was diagnosed to have first episode mania with complicated HSP. The details of treatment and possible neurobiology are discussed in this case report.

  11. [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.

  12. Recurrent IVF failure and hereditary thrombophilia.

    Science.gov (United States)

    Safdarian, Leila; Najmi, Zahra; Aleyasin, Ashraf; Aghahosseini, Marzieh; Rashidi, Mandana; Asadollah, Sara

    2014-07-01

    The largest percentage of failed invitro fertilization (IVF (cycles, are due to lack of implantation. As hereditary thrombophilia can cause in placentation failure, it may have a role in recurrent IVF failure. Aim of this case-control study was to determine whether hereditary thrombophilia is more prevalent in women with recurrent IVF failures. Case group comprised 96 infertile women, with a history of recurrent IVF failure. Control group was comprised of 95 healthy women with proven fertility who had conceived spontaneously. All participants were assessed for the presence of inherited thrombophilias including: factor V Leiden, methilen tetrahydrofolate reductase (MTHFR) mutation, prothrombin mutation, homocystein level, protein S and C deficiency, antithrombin III (AT-III) deficiency and plasminogen activator inhibitor-1 (PAI-1) mutation. Presence of thrombophilia was compared between groups. Having at least one thrombophilia known as a risk factor for recurrent IVF failure (95% CI=1.74-5.70, OR=3.15, p=0.00). Mutation of factor V Leiden (95% CI=1.26-10.27, OR=3.06, P=0.01) and homozygote form of MTHFR mutation (95% CI=1.55-97.86, OR=12.33, p=0.05) were also risk factors for recurrent IVF failure. However, we could not find significant difference in other inherited thrombophilia's. Inherited thrombophilia is more prevalent in women with recurrent IVF failure compared with healthy women. Having at least one thrombophilia, mutation of factor V Leiden and homozygote form of MTHFR mutation were risk factors for recurrent IVF failure.

  13. 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.

  14. Angioedema hereditario en Medellín, Colombia: evaluación clínica y de la calidad de vida

    Directory of Open Access Journals (Sweden)

    María Dulfary Sánchez

    2015-09-01

    Conclusión. Este estudio provee información sobre la primera familia caracterizada con angioedema hereditario de tipo 1 en el Valle de Aburrá, Colombia. Aunque para ello se usó un instrumento genérico, se confirmó, además, el efecto negativo de la enfermedad en la calidad de vida de los individuos que la padecen.

  15. Mitochondrial genetics and therapeutic overview of Leber's hereditary optic neuropathy

    Science.gov (United States)

    Manickam, Agaath Hedina; Michael, Minu Jenifer; Ramasamy, Sivasamy

    2017-01-01

    Leber's hereditary optic neuropathy (LHON) is a common inherited mitochondrial disorder that is characterized by the degeneration of the optic nerves, leading to vision loss. The major mutations in the mitochondrial genes ND1, ND4, and ND6 of LHON subjects are found to increase the oxidative stress experienced by the optic nerve cell, thereby leading to nerve cell damage. Accurate treatments are not available and drugs that are commercially available like Idebenone, EPI-743, and Bendavia with their antioxidant role help in reducing the oxidative stress experienced by the cell thereby preventing the progression of the disease. Genetic counseling plays an effective role in making the family members aware of the inheritance pattern of the disease. Gene therapy is an alternative for curing the disease but is still under study. This review focuses on the role of mitochondrial genes in causing LHON and therapeutics available for treating the disease. A systematic search has been adopted in various databases using the keywords “LHON,” “mitochondria,” “ND1,” “ND4,” “ND6,” and “therapy” and the following review on mitochondrial genetics and therapeutics of LHON has been developed with obtained articles from 1988 to 2017. PMID:29133631

  16. Mitochondrial genetics and therapeutic overview of Leber's hereditary optic neuropathy

    Directory of Open Access Journals (Sweden)

    Agaath Hedina Manickam

    2017-01-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a common inherited mitochondrial disorder that is characterized by the degeneration of the optic nerves, leading to vision loss. The major mutations in the mitochondrial genes ND1, ND4, and ND6 of LHON subjects are found to increase the oxidative stress experienced by the optic nerve cell, thereby leading to nerve cell damage. Accurate treatments are not available and drugs that are commercially available like Idebenone, EPI-743, and Bendavia with their antioxidant role help in reducing the oxidative stress experienced by the cell thereby preventing the progression of the disease. Genetic counseling plays an effective role in making the family members aware of the inheritance pattern of the disease. Gene therapy is an alternative for curing the disease but is still under study. This review focuses on the role of mitochondrial genes in causing LHON and therapeutics available for treating the disease. A systematic search has been adopted in various databases using the keywords “LHON,” “mitochondria,” “ND1,” “ND4,” “ND6,” and “therapy” and the following review on mitochondrial genetics and therapeutics of LHON has been developed with obtained articles from 1988 to 2017.

  17. Study of serum hepcidin in hereditary hemolytic anemias.

    Science.gov (United States)

    El Beshlawy, Amal; Alaraby, Ibrahim; Abdel Kader, Mohamed S E M; Ahmed, Dina H; Abdelrahman, Hossam E M

    2012-01-01

    The aim of this study was to assess the level of hepcidin in hereditary chronic hemolytic anemias and to correlate the serum hepcidin levels to the need for blood transfusions (frequency of blood transfusions and the serum ferritin level). Seventy pediatric patients with hereditary chronic hemolytic anemias, attending to hematology clinics of Cairo University and Misr University for Science and Technology (MUST) hospitals were the subjects of this study [53 patients with β-thalassemia major (β-TM), 10 patients with β-thalassemia intermedia (β-TI), four patients with congenital spherocytosis and three patients with sickle cell disease) (38 males and 32 females)]; their ages ranged from 1-14 years. Seventy normal children, age- and sex-matched, served as the control group. The results of this study revealed decreased hepcidin levels in patients (all types of congenital chronic hemolytic anemias) [mean ± SD (standard deviation) = 22.9 ± 6.0] compared to controls (mean ± SD = 132.4 ± 16.7) with highly significant statistical difference in between. Hepcidin levels were higher in β-TM patients (mean ± SD = 23.7 ± 6.2) than in β-TI patients (mean ± SD = 21.8 ± 4.0), the hepcidin to ferritin ratio was significantly less than one. In β-TM patients, the mean ± SD was 0.03 ± 0.004, and in β-TI patients the mean ± SD = 0.025 ± 0.002, with highly significant statistical difference with hepcidin-to-ferritin ratios in controls being mean ± SD = 2.3 ± 0.7. Hepcidin and hepcidin/ferritin ratios can be used as good markers of hemolytic anemia and iron overload as they have very high sensitivity (99.0 and 99.0%, respectively) and very high specificity (98.0 and 97.0%, respectively). Our findings highlight the potential usefulness of hepcidin measurement as a diagnostic tool. The use of hepcidin as an adjuvant therapy with iron chelators is important as it has a vital role in combating hemosidrosis.

  18. Hereditary predisposition to ovarian cancer, looking beyond BRCA1/BRCA2.

    Science.gov (United States)

    Minion, Lindsey E; Dolinsky, Jill S; Chase, Dana M; Dunlop, Charles L; Chao, Elizabeth C; Monk, Bradley J

    2015-04-01

    Genetic predisposition to ovarian cancer is well documented. With the advent of next generation sequencing, hereditary panel testing provides an efficient method for evaluating multiple genes simultaneously. Therefore, we sought to investigate the contribution of 19 genes identified in the literature as increasing the risk of hereditary breast and ovarian cancer (HBOC) in a BRCA1 and BRCA2 negative population of patients with a personal history of breast and/or ovarian cancer by means of a hereditary cancer panel. Subjects were referred for multi-gene panel testing between February 2012 and March 2014. Clinical data was ascertained from requisition forms. The incidence of pathogenic mutations (including likely pathogenic), and variant of unknown significance were then calculated for each gene and/or patient cohort. In this cohort of 911 subjects, panel testing identified 67 mutations. With 7.4% of subjects harboring a mutation on this multi-gene panel, the diagnostic yield was increased, compared to testing for BRCA1 and BRCA2 mutations alone. In the ovarian cancer probands, the most frequently mutated genes were BRIP1 (n=8; 1.72%) and MSH6 (n=6; 1.29%). In the breast cancer probands, mutations were most commonly observed in CHEK2 (n=9; 2.54%), ATM (n=3; 0.85%), and TP53 (n=3; 0.85%). Although further studies are needed to clarify the exact management of patients with a mutation in each gene, this study highlights information that can be captured with panel testing and provides support for incorporation of panel testing into clinical practice. Copyright © 2015. Published by Elsevier Inc.

  19. Hereditary leiomyomatosis and renal cell cancer: Cutaneous lesions & atypical fibroids

    Directory of Open Access Journals (Sweden)

    Pietro Bortoletto

    2017-07-01

    Precis: 27-year-old woman with multiple cutaneous lesions is found to have uterine leiomyomas and undergoes robotic myomectomy. Genetic testing of uterine leiomyomas reveals mutation in fumarate hydratase, etiologic in hereditary leiomyomatosis and renal cell cancer (HLRCC.

  20. 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.

  1. Genotype–phenotype correlations in Leber hereditary optic neuropathy

    National Research Council Canada - National Science Library

    Tońska, Katarzyna; Kodroń, Agata; Bartnik, Ewa

    2010-01-01

    Leber hereditary optic neuropathy (LHON), acute or subacute vision loss due to retinal ganglion cell death which in the long run leads to optic nerve atrophy is one of the most widely studied maternally inherited diseases caused...

  2. Relapsing Acute Axonal Neuropathy in Hereditary Fructose Intolerance.

    Science.gov (United States)

    Maitre, Anna; Maw, Anna; Ramaswami, Uma; Morley, Sarah L

    2016-11-01

    A severe neurological abnormality has not been previously described in individuals with hereditary fructose intolerance, which typically presents early in childhood with severe metabolic acidosis and hypoglycemia. We describe a boy who by age five years had required multiple admissions to the pediatric intensive care unit for an aggressive and atypical, relapsing and remitting neuropathy with features of acute motor axonal neuropathy (AMAN). It was later discovered that he also had undiagnosed hereditary fructose intolerance, and the severity and frequency of his neurological episodes diminished following an exclusion diet. His asymptomatic younger brother was diagnosed with hereditary fructose intolerance on screening. He is on a fructose-free diet and has not developed neurological symptoms. Ongoing low-level exposure to fructose prior to diagnosis may have contributed to our patient's neurological dysfunction. Early diagnosis and treatment may prevent neurological complications of hereditary fructose intolerance. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Antiretroviral therapy-induced Leber's hereditary optic neuropathy ...

    African Journals Online (AJOL)

    Nucleoside reverse transcriptase inhibitors (NRTIs) such as zidovudine and stavudine have known mitochondrial toxicity and can cause mitochondrial myopathies, neuropathies, hyperlactataemia, and can induce mitochondrial genetic disorders. Individuals with the mutation for Leber's hereditary optic neuropathy (LHON), ...

  4. Allelic variants of hereditary prions: The bimodularity principle.

    Science.gov (United States)

    Tikhodeyev, Oleg N; Tarasov, Oleg V; Bondarev, Stanislav A

    2017-01-02

    Modern biology requires modern genetic concepts equally valid for all discovered mechanisms of inheritance, either "canonical" (mediated by DNA sequences) or epigenetic. Applying basic genetic terms such as "gene" and "allele" to protein hereditary factors is one of the necessary steps toward these concepts. The basic idea that different variants of the same prion protein can be considered as alleles has been previously proposed by Chernoff and Tuite. In this paper, the notion of prion allele is further developed. We propose the idea that any prion allele is a bimodular hereditary system that depends on a certain DNA sequence (DNA determinant) and a certain epigenetic mark (epigenetic determinant). Alteration of any of these 2 determinants may lead to establishment of a new prion allele. The bimodularity principle is valid not only for hereditary prions; it seems to be universal for any epigenetic hereditary factor.

  5. Identification of a hereditary system with distributed delay

    NARCIS (Netherlands)

    Bagchi, Arunabha

    1985-01-01

    We study the identification problem that arises in a linear hereditary system with distributed delay. This involves estimating an infinite-dimensional parameter and we use the method of sieves, proposed by Grenander, to solve this problem.

  6. Targeted high throughput sequencing in hereditary ataxia and spastic paraplegia

    OpenAIRE

    Iqbal, Zafar; Rydning, Siri L.; Wedding, Iselin M.; Koht, Jeanette; Pihlstr?m, 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%)...

  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. Bile acid metabolism in hereditary forms of hypertriglyceridemia: evidence for an increased synthesis rate in monogenic familial hypertriglyceridemia.

    OpenAIRE

    Angelin, B; Hershon, K S; Brunzell, J D

    1987-01-01

    This study was undertaken to characterize bile acid metabolism in hereditary forms of hypertriglyceridemia. Ten hypertriglyceridemic patients (type IV phenotype) with familial combined hyperlipidemia and 7 patients with monogenic familial hypertriglyceridemia (FHTG) were compared with 18 healthy controls; all subjects were males. Pool size, synthesis rate, and fractional catabolic rate of cholic and chenodeoxycholic acids were determined with an isotope dilution technique. Patients with FHTG ...

  9. PREDICTIVE ROLE OF CONNEXIN 40 IN THE PATHOGENESIS OF HEREDITARY SICK SINUS SYNDROME

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    S. Yu. Nikulina

    2011-01-01

    Full Text Available Aim. To study the association of hereditary sick sinus syndrome (SSS with connexin 40 gene (Cx40 polymorphism. Material and methods. 29 families with hereditary SSS were involved into prospective study. Probands were 20 women and 9 men (aged 58±0.15. Relatives, I-III degree of kinship, were 65 men and 68 women (aged 39±0.13. Clinical and instrumental examination was performed in all probands and their relatives. Diagnosis of SSS was verified by transesophageal atrial electrostimulation. Molecular genetic investigation of SSS patients and their relatives was carried out in laboratory of medical genetics of Research Institute of Therapy , Siberian Branch of Russian Academy of Medical Sciences. Results. 71 SSS patients, 44 their healthy relatives, I-III degree of kinship, 197 subjects of control group were genotyped for the polymorphism of 44G>A of gene Cx40. According to allele-specific polymerase chain reaction 3 types of genotypes ADRA2B (II — homozygous wild, ID — heterozygous, DD — homozygous mutant were found in SSS patients, their relatives and healthy subjects of control group. Conclusion. Significant predominance of the heterozygous genotype 44G>A was found in SSS (45,07±5,9% patients in comparison with subjects of the control group (29,44±3,2%.

  10. Secondary post-geniculate involvement in Leber's hereditary optic neuropathy.

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    Giovanni Rizzo

    Full Text Available Leber's hereditary optic neuropathy (LHON is characterized by retinal ganglion cell (RGC degeneration with the preferential involvement of those forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the post-geniculate visual pathway in LHON patients. We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at level of optic radiation (OR. Prefrontal and cerebellar white matter were also analyzed as internal controls. Furthermore, we studied the optic nerve and the lateral geniculate nucleus (LGN in post-mortem specimens obtained from a severe case of LHON compared to an age-matched control. Mean diffusivity values of affected patients were higher than unaffected mutation carriers (P<0.05 and healthy subjects (P<0.01 in OR and not in the other brain regions. Increased OR diffusivity was associated with both disease duration (B = 0.002; P<0.05 and lack of recovery of visual acuity (B = 0.060; P<0.01. Post-mortem investigation detected atrophy (41.9% decrease of neuron soma size in the magnocellular layers and 44.7% decrease in the parvocellular layers and, to a lesser extent, degeneration (28.5% decrease of neuron density in the magnocellular layers and 28.7% decrease in the parvocellular layers in the LHON LGN associated with extremely severe axonal loss (99% in the optic nerve. The post-geniculate involvement in LHON patients is a downstream post-synaptic secondary phenomenon, reflecting de-afferentation rather than a primary neurodegeneration due to mitochondrial dysfunction of LGN neurons.

  11. Hereditary deficiency of protein C or protein S confers increased risk of arterial thromboembolic events at a young age - Results from a large family cohort study

    NARCIS (Netherlands)

    Mahmoodi, Bakhtawar K.; Brouwer, Jan-Leendert P.; Veeger, Nic J. G. M.; van der Meer, Jan

    2008-01-01

    Background-Whether hereditary protein S, protein C, or antithrombin deficiency is associated with arterial thromboembolism (ATE) and whether history of venous thromboembolism in these subjects predisposes them to subsequent ATE have yet to be determined. Methods and Results-On the basis of pedigree

  12. Hereditary deficiency of protein C or protein S confers increased risk of arterial thromboembolic events at a young age: results from a large family cohort study.

    NARCIS (Netherlands)

    Mahmoodi, B.K.; Brouwer, J.L.; Veeger, N.J.; Meer, J.W.M. van der

    2008-01-01

    BACKGROUND: Whether hereditary protein S, protein C, or antithrombin deficiency is associated with arterial thromboembolism (ATE) and whether history of venous thromboembolism in these subjects predisposes them to subsequent ATE have yet to be determined. METHODS AND RESULTS: On the basis of

  13. [Hereditary factors in attention deficit hyperactivity disorder].

    Science.gov (United States)

    Fliers, E A; Franke, B; Buitelaar, J K

    2005-07-30

    Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by concentration problems, hyperactivity and impulsivity. Disturbances in dopamine and/or noradrenalin neurotransmission are probably the underlying pathophysiological mechanisms of ADHD. Around 80% of variants of the phenotype can be ascribed to hereditary factors. There are various chromosomal loci containing ADHD genes. They partially overlap the loci found in linkage studies on dyslexia and autism. It seems likely that a number of genetic variants, each with a small effect size, in combination with gene-environment interactions predispose to ADHD. There is a high degree of phenotypical heterogeneity among people with ADHD. Finding endophenotypes may improve the power of genetic studies. Endophenotypes are specific expressions of the underlying pathophysiology, intermediate between gene and phenotype. Neuro-imaging studies in children with ADHD have indicated abnormalities in frontostriatal, temporal and cerebellar volume. Unaffected brothers and sisters show the same cerebral abnormalities, but not the cerebellar abnormalities. These brain abnormalities together with specific neuropsychological features could be ADHD endophenotypes.

  14. 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.

  15. 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

  16. Molecular Diagnostic and Pathogenesis of Hereditary Hemochromatosis

    Science.gov (United States)

    Santos, Paulo C. J. L.; Krieger, Jose E.; Pereira, Alexandre C.

    2012-01-01

    Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by enhanced intestinal absorption of dietary iron. Without therapeutic intervention, iron overload leads to multiple organ damage such as liver cirrhosis, cardiomyopathy, diabetes, arthritis, hypogonadism and skin pigmentation. Most HH patients carry HFE mutant genotypes: homozygosity for p.Cys282Tyr or p.Cys282Tyr/p.His63Asp compound heterozygosity. In addition to HFE gene, mutations in the genes that encode hemojuvelin (HJV), hepcidin (HAMP), transferrin receptor 2 (TFR2) and ferroportin (SLC40A1) have been associated with regulation of iron homeostasis and development of HH. The aim of this review was to identify the main gene mutations involved in the pathogenesis of type 1, 2, 3 and 4 HH and their genetic testing indication. HFE testing for the two main mutations (p.Cys282Tyr and p.His63Asp) should be performed in all patients with primary iron overload and unexplained increased transferrin saturation and/or serum ferritin values. The evaluation of the HJV p.Gly320Val mutation must be the molecular test of choice in suspected patients with juvenile hemochromatosis with less than 30 years and cardiac or endocrine manifestations. In conclusion, HH is an example that genetic testing can, in addition to performing the differential diagnostic with secondary iron overload, lead to more adequate and faster treatment. PMID:22408404

  17. Molecular Diagnostic and Pathogenesis of Hereditary Hemochromatosis

    Directory of Open Access Journals (Sweden)

    Paulo C. J. L. Santos

    2012-02-01

    Full Text Available Hereditary hemochromatosis (HH is an autosomal recessive disorder characterized by enhanced intestinal absorption of dietary iron. Without therapeutic intervention, iron overload leads to multiple organ damage such as liver cirrhosis, cardiomyopathy, diabetes, arthritis, hypogonadism and skin pigmentation. Most HH patients carry HFE mutant genotypes: homozygosity for p.Cys282Tyr or p.Cys282Tyr/p.His63Asp compound heterozygosity. In addition to HFE gene, mutations in the genes that encode hemojuvelin (HJV, hepcidin (HAMP, transferrin receptor 2 (TFR2 and ferroportin (SLC40A1 have been associated with regulation of iron homeostasis and development of HH. The aim of this review was to identify the main gene mutations involved in the pathogenesis of type 1, 2, 3 and 4 HH and their genetic testing indication. HFE testing for the two main mutations (p.Cys282Tyr and p.His63Asp should be performed in all patients with primary iron overload and unexplained increased transferrin saturation and/or serum ferritin values. The evaluation of the HJV p.Gly320Val mutation must be the molecular test of choice in suspected patients with juvenile hemochromatosis with less than 30 years and cardiac or endocrine manifestations. In conclusion, HH is an example that genetic testing can, in addition to performing the differential diagnostic with secondary iron overload, lead to more adequate and faster treatment.

  18. Consanguinity and hereditary hearing loss in Qatar.

    Science.gov (United States)

    Girotto, Giorgia; Mezzavilla, Massimo; Abdulhadi, Khalid; Vuckovic, Dragana; Vozzi, Diego; Khalifa Alkowari, Moza; Gasparini, Paolo; Badii, Ramin

    2014-01-01

    Qatar is a sovereign state located on the Eastern coast of the Arabian Peninsula in the Persian Gulf. Its native population consists of 3 major subgroups: people of Arabian origin or Bedouins, those from an Eastern or Persian ancestry and individuals with African admixture. Historically, all types of consanguineous marriages have been and still are common in the Qatari population, particularly among first and double-first cousins. Thus, there is a higher risk for most inherited diseases including hereditary hearing loss (HHL). In particular, a hearing loss prevalence of 5.2% has been reported in Qatar, with parental consanguinity being more common among affected individuals as compared with unaffected ones. Our recent molecular results confirm a high homogeneity and level of inbreeding in Qatari HHL patients. Among all HHL genes, GJB2, the major player worldwide, accounts for a minor proportion of cases and at least 3 additional genes have been found to be mutated in Qatari patients. Interestingly, one gene, BDP1, has been described to cause HHL only in this country. These results point towards an unexpected level of genetic heterogeneity despite the high level of inbreeding. This review provides an up-to-date picture of HHL in Qatar and of the impact of consanguinity on this disease. © 2014 S. Karger AG, Basel.

  19. Hereditary Ovarian Cancer and Risk Reduction.

    Science.gov (United States)

    Andrews, Lesley; Mutch, David G

    2017-05-01

    Mutations in BRCA1 and BRCA2 account for hereditary breast and ovarian cancer syndrome in a majority of families and 14% of epithelial ovarian cancer cases. Despite next-generation sequencing, other identified genes (Lynch Syndrome, RAD51C, RAD51D, and BRIP1) account for only a small proportion of cases. The risk of ovarian cancer by age 70 is approximately 40% for BRCA1 and 18% for BRCA2. Most of these cancers are high-grade serous cancers that predominantly arise in the fimbriae of the fallopian tube. Ovarian screening does not improve outcomes, so women at high risk are recommended to undergo risk-reducing salpingo-oophorectomy around the age of 40, followed by hormone replacement therapy (HRT). Specimens should be carefully examined for occult malignancy. Mutation carriers may benefit from newly developed poly ADP ribose polymerase inhibitors. Genetic testing should only be performed after careful counseling, particularly if testing involves the testing of panels of genes that may identify unsuspected disease predisposition or confusing variants of uncertain significance. Copyright © 2017. Published by Elsevier Ltd.

  20. Hereditary multiple exostoses of the hip.

    Science.gov (United States)

    El-Fiky, Tarek A M; Chow, Wang; Li, Yun Hoi; To, Michael

    2009-08-01

    To assess the radiographic features of 36 hips with hereditary multiple exostoses (HME). Hip parameters of 12 males and 6 females (36 hips) aged 2 to 28 years with HME were assessed using anteroposterior radiographs. The recorded features included the sites of osteochondromas, the femoral head/neck ratio, the Reimer's migration percentage, Sharp's acetabular angle, the centre edge angle, the femoral neck-shaft angle, and degenerative changes. 15 of the 18 patients were asymptomatic; 3 complained of pain (2 underwent excision or bone biopsy); no lesion was malignant. Osteochondromas were most commonly located in the femur followed by the ilium; only one was intra-articular. 32 hips had coxa valga; 26 had an abnormal Reimer's migration percentage; 17 had an abnormal Sharp's acetabular angle; 12 had an abnormal centre edge angle; 32 had an abnormal femoral neck-shaft angle; and 6 had degenerative changes. Acetabular and femoral dysplasia as well as subluxation are common in patients with HME. Borderline subluxated hips and those with marked coxa valga and/or acetabular dysplasia should be closely monitored to determine the need for surgery in the future. Subluxated hips should be operated on early, particularly in children and symptomatic adults.

  1. The hip in hereditary multiple exostoses.

    Science.gov (United States)

    Porter, D E; Benson, M K; Hosney, G A

    2001-09-01

    We defined the characteristics of dysplasia and coxa valga in hereditary multiple exostoses (HME) by radiological analysis of 24 hips in 12 patients. The degree and effect of the 'osteochondroma load' around the hip were quantified. We investigated the pathology of the labrum and the incidence of osteoarthritis and of malignant change in these patients. Coxa valga and dysplasia were common with a median neck-shaft angle of 156 degrees, a median centre-edge angle of 23 degrees and Sharp's acetabular angle of 44 degrees. There was overgrowth of the femoral neck with a significantly greater ratio of the neck/shaft diameter in HME than in the control hips (p coxa valga (p coxa valga. No correlation was found between dysplasia and coxa valga. These data suggest that HME may cause anomalies of the hip as a reflection of a generalised inherited defect, but also support the theory that osteochondromas may themselves precipitate some of the characteristic features of HME around the hip.

  2. Modern diagnostic approach to hereditary xanthinuria.

    Science.gov (United States)

    Mraz, Martin; Hurba, Olha; Bartl, Josef; Dolezel, Zdenek; Marinaki, Anthony; Fairbanks, Lynette; Stiburkova, Blanka

    2015-02-01

    Hereditary xanthinuria (HX) is a rare inherited disorder caused by a deficiency of xanthine dehydrogenase/oxidase (XDH/XO). Missing XDH/XO activity leads to undetectable levels of uric acid excessively replaced by xanthine in serum/urine. The allopurinol loading test has been traditionally used to differentiate between HX types I and II. Final confirmation of HX has been based on the biopsy finding of the absent XDH/XO activity in the small intestine or liver. We present the clinical, biochemical, ultrasound and molecular genetics findings in three new patients with HX and suggest a simple three-step approach to be used for diagnosis, typing and confirmation of HX. In the first step, the diagnosis of HX is determined by extremely low serum/urinary uric acid excessively replaced by xanthine. Second, HX is typed using urinary metabolomics. Finally, the results are confirmed by molecular genetics. We advocate for this safe and non-invasive diagnostic algorithm instead of the traditional allopurinol loading test and intestinal or liver biopsy used in the past.

  3. 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.

  4. Risk factors for cancer in hereditary pancreatitis. International Hereditary Pancreatitis Study Group.

    Science.gov (United States)

    Lowenfels, A B; Maisonneuve, P; Whitcomb, D C

    2000-05-01

    Hereditary pancreatitis is a rare form of pancreatitis, accounting for approximately 1% of all types of pancreatitis. It is inherited as an autosomal dominant disease, with incomplete penetrance. The genetic defect is believed to be caused by mutations in the trypsinogen gene. Patients who inherit the disorder suffer from a form of pancreatitis that resembles other types of pancreatitis, but the age of onset is much earlier. Sixteen biopsy-proven pancreatic cancers have developed in a cohort of 412 patients with a median follow-up period of 18 years (interquartile range, 7 to 30 years) since the onset of symptoms. Compared with the background population, the risk of pancreatic cancer is approximately 50 to 60 times greater than expected. Smoking appears to be an additional risk factor in these patients: Smoking increases the risk of developing pancreatic cancer and lowers the age of onset by approximately 20 years. Patients with hereditary pancreatitis are urged to avoid smoking because it greatly increases the risk of pancreatic cancer and to avoid alcohol, a known risk factor for all forms of pancreatitis.

  5. Copy number variation in ALOX5 and PTGER1 is associated with NSAIDs-induced urticaria and/or angioedema.

    Science.gov (United States)

    Plaza-Serón, María Del Carmen; Ayuso, Pedro; Pérez-Sánchez, Natalia; Doña, Inmaculada; Blanca-Lopez, Natalia; Flores, Carlos; Galindo, Luisa; Molina, Ana; Perkins, James R; Cornejo-García, Jose A; Agúndez, Jose A; García-Martín, Elena; Campo, Paloma; Canto, Gabriela; Blanca, Miguel

    2016-06-01

    Cross-intolerance to NSAIDs is a class of drug hypersensitivity reaction, of which NSAIDs-induced urticaria and/or angioedema (NIUA) are the most frequent clinical entities. They are considered to involve dysregulation of the arachidonic acid pathway; however, this mechanism has not been confirmed for NIUA. In this work, we assessed copy number variations (CNVs) in eight of the main genes involved in the arachidonic acid pathway and their possible genetic association with NIUA. CNVs in ALOX5, LTC4S, PTGS1, PTGS2, PTGER1, PTGER2, PTGER3, and PTGER4 were analyzed using TaqMan copy number assays. Genotyping was carried out by real-time quantitative PCR. Individual genotypes were assigned using the CopyCaller Software. Statistical analysis was carried out using GraphPad prism 5, PLINK, EPIDAT, and R version 3.1.2. A total of 151 cases and 139 controls were analyzed during the discovery phase and 148 cases and 140 controls were used for replication. CNVs in open reading frames were found for ALOX5, PTGER1, PTGER3, and PTGER4. Statistically significant differences in the CNV frequency between NIUA and controls were found for ALOX5 (Pc=0.017) and PTGER1 (Pc=1.22E-04). This study represents the first analysis showing an association between CNVs in exonic regions of ALOX5 and PTGER1 and NIUA. This suggests a role of CNVs in this pathology that should be explored further.

  6. [Significance of ophthalmological imaging in common hereditary retinal diseases].

    Science.gov (United States)

    Kortüm, K; Kernt, M; Reznicek, L

    2013-03-01

    Over the past years, a significant progress in genetic, functional and imaging diagnostics in hereditary retinal diseases has been made. Optical coherence tomography (OCT) as well as fundus autofluorescence (FAF) allow for high-resolution, non-invasive imaging - from various perspectives - of retinal and choroidal layers of the posterior fundus. Both techniques have gained more and more significance in the diagnosis of hereditary retinal diseases. Of all patients presented in this review, extensive family history was taken and a clinical ophthalmological examination performed. OCT scans as well as FAF images were acquired and compared to results of other functional and molecular genetic tests in the context of each disease. The presented cases in this review addressing hereditary retinal diseases (Best's disease, Stargardt's disease, cone-rod dystrophy, retinitis pigmentosa, achromatopsia, and X-linked retinoschisis) show the significance of ophthalmic imaging (OCT + FAF) for a targeted diagnosis of hereditary retinal diseases. The described imaging techniques (OCT + FAF) are becoming more and more important in the diagnosis of hereditary retinal diseases. Due to increasing availability of the devices, earlier detection of typical morphological changes not seen in clinical fundoscopy is feasible. Georg Thieme Verlag KG Stuttgart · New York.

  7. Characteristics of gene mutation in Chinese patients with hereditary hemochromatosis

    Directory of Open Access Journals (Sweden)

    LYU Tingxia

    2016-08-01

    Full Text Available ObjectiveTo investigate the characteristics of gene mutation in Chinese patients with hereditary hemochromatosis (HH. MethodsA total of 9 patients with HH who visited Beijing Friendship Hospital, Capital Medical University from January 2013 to December 2015 were enrolled. The genomic DNA was extracted, and PCR amplification and Sanger sequencing were performed for all the exons of four genotypes of HH, i.e., HFE (type Ⅰ, HJV (type ⅡA, HAMP (type ⅡB, TFR2 (type Ⅲ, and SLC40A1 (type Ⅳ to analyze gene mutations. A total of 50 healthy subjects were enrolled as control group to analyze the prevalence of identified gene mutations in a healthy population. ResultsOf all patients, 2 had H63D mutation of HFE gene in type Ⅰ HH, 1 had E3D mutation of HJV gene in type ⅡA HH, 2 had I238M mutation of TFR2 gene in type Ⅲ HH, and 1 had IVS 3+10 del GTT splice mutation of SLC40A1 gene in type Ⅳ HH. No patients had C282Y mutation of HFE gene in type Ⅰ HH which was commonly seen in European and American populations. Five patients had no missense mutation or splice mutation. In addition, it was found in a family that a HH patient had E3D mutation of HJV gene, H63D mutation of HFE gene, and I238M mutation of TFR2 gene, but the healthy brother and sister carrying two of these mutations did not had the phenotype of HH. ConclusionHH gene mutations vary significantly across patients of different races, and non-HFE-HH is dominant in the Chinese population. There may be HH genes which are different from known genes, and further investigation is needed.

  8. Childhood-onset Leber hereditary optic neuropathy.

    Science.gov (United States)

    Majander, Anna; Bowman, Richard; Poulton, Joanna; Antcliff, Richard J; Reddy, M Ashwin; Michaelides, Michel; Webster, Andrew R; Chinnery, Patrick F; Votruba, Marcela; Moore, Anthony T; Yu-Wai-Man, Patrick

    2017-11-01

    The onset of Leber hereditary optic neuropathy (LHON) is relatively rare in childhood. This study describes the clinical and molecular genetic features observed in this specific LHON subgroup. Our retrospective study consisted of a UK paediatric LHON cohort of 27 patients and 69 additional cases identified from a systematic review of the literature. Patients were included if visual loss occurred at the age of 12 years or younger with a confirmed pathogenic mitochondrial DNA mutation: m.3460G>A, m.11778G>A or m.14484T>C. In the UK paediatric LHON cohort, three patterns of visual loss and progression were observed: (1) classical acute (17/27, 63%); (2) slowly progressive (4/27, 15%); and (3) insidious or subclinical (6/27, 22%). Diagnostic delays of 3-15 years occurred in children with an insidious mode of onset. Spontaneous visual recovery was more common in patients carrying the m.3460G>A and m.14484T>C mutations compared with the m.11778G>A mutation. Based a meta-analysis of 67 patients with available visual acuity data, 26 (39%) patients achieved a final best-corrected visual acuity (BCVA) ≥0.5 Snellen decimal in at least one eye, whereas 13 (19%) patients had a final BCVA <0.05 in their better seeing eye. Although childhood-onset LHON carries a relatively better visual prognosis, approximately 1 in 5 patients will remain within the visual acuity criteria for legal blindness in the UK. The clinical presentation can be insidious and LHON should be considered in the differential diagnosis when faced with a child with unexplained subnormal vision and optic disc pallor. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Hereditary gingival fibromatosis and growth retardation.

    Science.gov (United States)

    Bhowmick, S K; Gidvani, V K; Rettig, K R

    2001-01-01

    To describe two patients with hereditary gingival fibromatosis (HGF) and growth hormone deficiency and to review the literature on HGF and related endocrine abnormalities. We present case reports of two patients (first cousins)-an 8-year-old girl and a 13-year-old boy-with an existing diagnosis of HGF, who were assessed because of presumed growth failure. Both patients underwent growth hormone stimulation testing and more in-depth endocrine evaluation, including measurement of morning cortisol, adrenocorticotropic hormone (ACTH), and prolactin levels as well as thyroid function tests. An ACTH stimulation test was also performed. Radiologic evaluation included assessment of bone age and magnetic resonance imaging of the brain. In addition to HGF, both patients had short stature, subnormal growth velocity, and delayed bone age but no abnormalities on magnetic resonance imaging of the brain. Serum prolactin levels and results of thyroid function tests were normal. Subnormal growth hormone response was noted during hypoglycemia and pharmacologic stimuli with clonidine and levodopa. The female patient, who also had recurrent hypoglycemic episodes, had a suboptimal cortisol and ACTH response during hypoglycemia. On the ACTH stimulation test, she showed an inadequate cortisol response at 30 minutes but a normal response at 60 minutes. The male patient had normal morning cortisol and ACTH levels plus a normal response to ACTH stimulation. Both patients are responding well to treatment with growth hormone. The girl is also receiving cortisol replacement and has had no further episodes of hypoglycemia. Although HGF has been described as an isolated finding, it can occur as part of a syndrome, including infrequent endocrine abnormalities such as growth hormone insufficiency. The cause of the growth hormone deficiency remains unclear in these two patients. We believe that patients with HGF should be monitored carefully for a prolonged period for growth as well as other

  10. Hereditary Hemochromatosis and Transferrin Receptor 2

    Science.gov (United States)

    Chen, Juxing

    2011-01-01

    Background Multicellular organisms regulate the uptake of calories, trace elements, and other nutrients by complex feedback mechanisms. In the case of iron, the body senses internal iron stores, iron requirements for hematopoiesis, and inflammatory status, and regulates iron uptake by modulating the uptake of dietary iron from the intestine. Both the liver and the intestine participate in the coordination of iron uptake and distribution in the body. The liver senses inflammatory signals and iron status of the organism and secretes a peptide hormone, hepcidin. Under high iron or inflammatory conditions hepcidin levels increase. Hepcidin binds to the iron transport protein, ferroportin (FPN), promoting FPN internalization and degradation. Decreased FPN levels reduce iron efflux out of intestinal epithelial cells and macrophages into the circulation. Derangements in iron metabolism result in either the abnormal accumulation of iron in the body, or in anemias. The identification of the mutations that cause the iron overload disease, hereditary hemochromatosis (HH), or iron-refractory iron-deficiencey anemia has revealed many of the proteins used to regulate iron uptake. Scope of the review In this review we discuss recent data concerning the regulation of iron homeostasis in the body by the liver and how transferrin receptor 2 (TfR2) affects this process. Major conclusions TfR2 plays a key role in regulating iron homeostasis in the body. General significance The regulation of iron homeostasis is important. One third of the people in the world are anemic. HH is the most common inherited disease in people of Northern European origin and can lead to severe health complications if left untreated. PMID:21864651

  11. Optimal management of hereditary hemorrhagic telangiectasia

    Directory of Open Access Journals (Sweden)

    Garg N

    2014-10-01

    Full Text Available Neetika Garg,1 Monica Khunger,2 Arjun Gupta,3 Nilay Kumar4 1Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; 2Department of Medicine, All India Institute of Medical Sciences, New Delhi, India; 3Department of Medicine, UT Southwestern Medical Center, Dallas, TX, USA; 4Department of Medicine, Cambridge Health Alliance/Harvard Medical School, Cambridge, MA, USA Abstract: Hereditary hemorrhagic telangiectasia (HHT, also known by the eponym Osler–Weber–Rendu syndrome, is a group of related disorders inherited in an autosomal dominant fashion and characterized by the development of arteriovenous malformations (AVM in the skin, mucous membranes, and/or internal organs such as brain, lungs, and liver. Its prevalence is currently estimated at one in 5,000 to 8,000. Most cases are due to mutations in the endoglin (HHT1 or ACVRLK1 (HHT2 genes. Telangiectasias in nasal and gastrointestinal mucosa generally present with recurrent/chronic bleeding and iron deficiency anemia. Larger AVMs occur in lungs (~40%–60% of affected individuals, liver (~40%–70%, brain (~10%, and spine (~1%. Due to the devastating and potentially fatal complications of some of these lesions (for example, strokes and brain abscesses with pulmonary AVMs, presymptomatic screening and treatment are of utmost importance. However, due to the rarity of this condition, many providers lack an appreciation for the whole gamut of its manifestations and complications, age-dependent penetrance, and marked intrafamilial variation. As a result, HHT remains frequently underdiagnosed and many families do not receive the appropriate screening and treatments. This article provides an overview of the clinical features of HHT, discusses the clinical and genetic diagnostic strategies, and presents an up-to-date review of literature and detailed considerations regarding screening for visceral AVMs, preventive modalities, and treatment options. Keywords: arteriovenous

  12. Genetics Home Reference: hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis

    Science.gov (United States)

    ... Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis Printable PDF Open All Close All Enable Javascript ... Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (abbreviated POIKTMP ), is a disorder that affects many ...

  13. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis

    NARCIS (Netherlands)

    Vasen, HFA; Wijnen, JT; Menko, FH; Kleibeuker, JH; Taal, BG; Griffioen, G; Nagengast, FM; MeijersHeijboer, EH; Bertario, L; Varesco, L; Bisgaard, ML; Mohr, J; Fodde, R; Khan, PM

    Background & Aims: Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers, The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of

  14. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis

    NARCIS (Netherlands)

    Vasen, H. F.; Wijnen, J. T.; Menko, F. H.; Kleibeuker, J. H.; Taal, B. G.; Griffioen, G.; Nagengast, F. M.; Meijers-Heijboer, E. H.; Bertario, L.; Varesco, L.; Bisgaard, M. L.; Mohr, J.; Fodde, R.; Khan, P. M.

    1996-01-01

    Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers. The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of carriers within

  15. High prevalence of hereditary thrombotic thrombocytopenic purpura in central Norway: from clinical observation to evidence.

    OpenAIRE

    von Krogh A S; Quist-Paulsen P; Waage A; Langseth Ø O; Thorstensen K; Brudevold R; Tjønnfjord G E; Largiadèr C R; Lämmle B; Kremer Hovinga J A

    2016-01-01

    Essentials The population prevalence of hereditary thrombotic thrombocytopenic purpura (TTP) is unknown. We studied the prevalence of hereditary TTP and population frequencies of two ADAMTS 13 mutations. A high frequency of hereditary TTP related to ADAMTS 13 mutation c.4143_4144dupA was found. Vicinity of ABO blood group and ADAMTS 13 loci may facilitate screening of ADAMTS 13 mutations. Background Hereditary thrombotic thrombocytopenic purpura (TTP) caused by ADAMTS 13 mutations is a rare b...

  16. 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.

  17. 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.

  18. 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.

  19. [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.

  20. [Efficiency of color vision tests in hereditary dyschromatopsia: case report].

    Science.gov (United States)

    Fernandes, Luciene Chaves; Urbano, Lúcia Carvalho de Ventura

    2008-01-01

    The authors describe two cases of hereditary dyschromatopsia and discuss the efficiency of the color vision tests. The patients were disapproved in different federal public examinations because Ishihara's test diagnosed hereditary dyschromatopsia. Ophthalmological evaluation was normal. No symptoms related to dyschromatopsia were presented. Panels D15 and Roth D 28 were normal. Desaturated D 15 showed deuteranomaly in case one. In the second case the comparative color vision tests showed nonspecific disorder. The diagnosis of dyschromatopsia is complex. The authors recommend comparative color vision tests to complement the Ishihara test for a better understanding of the color deficiency.

  1. Mutator gene and hereditary non-polyposis colorectal cancer

    Science.gov (United States)

    de la Chapelle, Albert [Helsingfors, FI; Vogelstein, Bert [Baltimore, MD; Kinzler, Kenneth W [Baltimore, MD

    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.

  2. Considerações anestésicas perante um doente com angioedema hereditário: caso clínico

    OpenAIRE

    Vilaça, MJ; Coelho, M; Faísco, A; Carmona, C

    2016-01-01

    O angioedema hereditário (AEH), com uma prevalência estimada de 1:50000 pessoas, é uma doença rara mas potencialmente fatal. Pode se apresentar com edema sistêmico recorrente do tecido subcutâneo e das mucosas. Os doentes com AEH têm um risco acrescido de agudização clínica com o estresse cirúrgico, podem desenvolver síndromes de dificuldade respiratória por compromisso da via aérea e de instabilidade hemodinâmica. A abordagem perioperatória desses doentes requer intervenções e...

  3. Clinical features of pure hereditary spastic paraplegia

    Directory of Open Access Journals (Sweden)

    WEI Qian-qian

    2013-07-01

    Full Text Available Objective To study the clinical features and diagnostic methods of patients with pure hereditary spastic paraplegia (HSP. Methods Patients diagnosed with pure HSP from October 2006 to February 2013 admitted to Department of Neurology, West China Hospital, Sichuan University were included. The patients were assessed by the Spastic Paraplegia Rating Scale and the clinical features were reviewed. Results Thirty-three HSP patients (21 men and 12 women were included in the study. Thirteen patients (39.39% had family history of HSP and the most common genetic mode of the familial cases were autosomal dominant inheritance (11/13. The mean age of onset were (20.35 ± 15.55 years and the mean disease duration were (12.77 ± 9.83 years. All of the included patients presented with signs of impairment of the pyramidal tract such as increased muscular tone, tendon hyperreflexia and positive Babinski's sign of the lower limbs. Impairment of the pyramidal tract also presented in the upper limbs in some patients. Scissors gait appeared in 29 patients and feet deformity in 5 patients. Atrophy of thoracic cord on MRI were presented in 5 patients while 2 patients complicated with peripheral nerve damage. Four patients had a novel exon 10-17 deletion in SPG4 gene. There were no differences in onset age, disease duration and mean score of the Spastic Paraplegia Rating Scale between male and female patients as well as between patients with and without family history (P > 0.05, for all. Conclusion The onset age of pure HSP is variational and males are more common than females. The most common inheritance mode is autosomal dominant and most of the cases are characterized by impairment of the pyramidal tract of the lower limbs and occasionally bladder dysfunction and peripheral nerve damage. Gender and family history do not affect the clinical features. Clinical features, family history and spinal cord MRI will assist the correct diagnosis, and making a definite

  4. Spinal cord magnetic resonance imaging in autosomal dominant hereditary spastic paraplegia

    Energy Technology Data Exchange (ETDEWEB)

    Hedera, P. [University of Michigan, Department of Neurology, Ann Arbor, MI (United States); Vanderbilt University, Department of Neurology, Nashville, TN (United States); Eldevik, O.P.; Maly, P. [University of Michigan, Department of Radiology, Ann Arbor, MI (United States); Rainier, S. [University of Michigan, Department of Neurology, Ann Arbor, MI (United States); Fink, J.K. [University of Michigan, Department of Neurology, Ann Arbor, MI (United States); Ann Arbor Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Ann Arbor, MI (United States)

    2005-10-01

    Hereditary spastic paraplegia (HSP) is a genetically heterogeneous group of neurodegenerative disorders characterized by progressive lower extremity weakness and spasticity. HSP pathology involves axonal degeneration that is most pronounced in the terminal segments of the longest descending (pyramidal) and ascending (dorsal columns) tracts. In this study, we compared spinal cord magnetic resonance imaging (MRI) in 13 HSP patients with four different types of autosomal dominant hereditary spastic paraplegia (SPG3A, SPG4, SPG6, and SPG8) with age-matched control subjects. The cross-section area of HSP subjects at cervical level C2 was 59.42{+-}12.57 mm{sup 2} and at thoracic level T9 was 28.58{+-}5.25 mm{sup 2}. Both of these values were less than in the healthy controls (p<0.001). The degree of cord atrophy was more prominent in patients with SPG6 and SPG8 who had signs of severe cord atrophy (47.60{+-}6.58 mm{sup 2} at C2, 21.40{+-}2.4 mm{sup 2} at T9) than in subjects with SPG3 and SPG4 (66.0{+-}8.94 mm{sup 2} at C2, p<0.02; 31.75{+-}2.76 mm{sup 2} at T9, p<0.001). These observations indicate that spinal cord atrophy is a common finding in the four genetic types of HSP. Spinal cord atrophy was more severe in SPG6 and SPG8 HSP subjects than in other types of HSP we studied. This may suggest a different disease mechanism with more prominent axonal degeneration in these two types of HSP when compared with HSP due to spastin and atlastin mutations. (orig.)

  5. Índices eritrocitarios en la esferocitosis hereditaria Erythrocyte indexes in hereditary spherocytosis

    Directory of Open Access Journals (Sweden)

    Silvia Eandi Eberle

    2007-12-01

    Full Text Available La esferocitosis hereditaria es un grupo heterogéneo de desórdenes caracterizados por la variabilidad en la clínica, en los defectos proteicos del citoesqueleto eritrocitario y en el tipo de herencia. Se estudió la sensibilidad y especificidad de la concentración de hemoglobina corpuscular media (CHCM y el índice de amplitud de distribución eritrocitaria (ADE en el screening diagnóstico de la esferocitosis hereditaria. Noventa y cuatro pacientes fueron comparados con niños sanos de igual sexo y edad. Todos los índices se obtuvieron por impedancia eléctrica (autoanalizador hematológico Coulter JT. En los pacientes con esferocitosis hereditaria, la CHCM (35.67±1.33 g/dl y el ADE (20.60±4.5%, fueron significativamente más elevados que en el grupo control (CHCM 33.48±0.68 g/dl, p 0.000; ADE 13.22±0.9%, p 0.000. Con los valores de corte utilizados en nuestro laboratorio (CHCM ≥ 34.5 g/dl; ADE ≥ 14.5% ambos índices elevados mostraron una sensibilidad de 81% y una especificidad de 98.9% en el screening de esferocitosis hereditaria. La combinación de ambos índices es un excelente predictor para el diagnóstico de esferocitosis hereditaria.Hereditary spherocytosis is a group of heterogenous disorders characterized by variability in its clinical manifestations, membrane protein defects and inheritance. We analysed the sensitivity and specificity of mean corpuscular hemoglobin concentration (MCHC and red cell distribution width (RDW in the diagnostic screening of hereditary spherocytosis. Ninetyfour patients were compared to equal number of healthy, age-matched children. All indexes were derived from measurements obtained by aperture impedance (Coulter Counter Model JT. In patients with hereditary spherocytosis, MCHC (35.67±1.33 g/dl and RDW (20.60±4.5% were significantly higher than in normal control subjects (MCHC 33.48±0.68 g/dl, p: 0.000; RDW 13.22±0.9%, p: 0.000. By using a cutoff for the MCHC of 34.5 g/dl and for the RDW

  6. Targeted therapy for hereditary cancer syndromes: hereditary breast and ovarian cancer syndrome, Lynch syndrome, familial adenomatous polyposis, and Li-Fraumeni syndrome.

    Science.gov (United States)

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2014-12-01

    Cancer genetics has rapidly evolved in the last two decades. Understanding and exploring the several genetic pathways in the cancer cell is the foundation of targeted therapy. Several genomic aberrations have been identified and their role in carcinogenesis is being explored. In contrast to most cancers where these mutations are acquired, patients with hereditary cancer syndromes have inherited genomic aberrations. The understanding of the molecular pathobiology in hereditary cancer syndromes has advanced dramatically. In addition, many molecularly targeted therapies have been developed that could have potential roles in the treatment of patients with hereditary cancer syndromes. In this review, we outline the presentation, molecular biology, and possible targeted therapies for two of the most widely recognized hereditary cancer syndromes -- hereditary breast and ovarian cancer syndrome and hereditary non-polyposis colorectal cancer syndrome (Lynch syndrome). We will also discuss other syndromes such as familial adenomatous polyposis and Li-Fraumeni syndrome (TP53).

  7. Knowledge about breast cancer and hereditary breast cancer among nurses in a public hospital 1

    Science.gov (United States)

    Prolla, Carmen Maria Dornelles; da Silva, Patrícia Santos; Netto, Cristina Brinckmann Oliveira; Goldim, José Roberto; Ashton-Prolla, Patricia

    2015-01-01

    OBJECTIVE: To assess the knowledge of nurses involved in the care of oncology patients in a public university hospital, regarding breast cancer and hereditary breast cancer, and to verify the use of such knowledge in their daily practice. METHODS: This is a descriptive cross-sectional study. Data were obtained through a structured, self-administered questionnaire. Out of 154 nurses, 137 (88.9%) agreed to participate in the study. Two questionnaires were excluded such that 135 questionnaires were analyzed. RESULTS: The global percentage of correct answers was not associated with age (p=0.173) or degree/specialization (p=0.815). Questions were classified into categories. In categories involving knowledge of established breast cancer risk factors and indicators of hereditary breast cancer, the rate of correct answers was 65.8% and 66.4%, respectively. On the practice of genetic counseling, 40.7% of those interviewed were not sure about the definition of genetic counseling and 78.5% reported never having identified or referred a patient at genetic risk for specialized risk assessment. Practice of educational actions regarding this subject was reported by 48.5% of those interviewed. CONCLUSION: This study reinforces the need to develop qualifying actions for nurses, so that strategies to control breast cancer become effective in their health care practice. PMID:25806636

  8. Exome sequencing released a case of X-linked adrenoleukodystrophy mimicking recessive hereditary spastic paraplegia.

    Science.gov (United States)

    Zhan, Zi-Xiong; Liao, Xin-Xin; Du, Juan; Luo, Ying-Ying; Hu, Zhao-Ting; Wang, Jun-Ling; Yan, Xin-Xiang; Zhang, Jian-Guo; Dai, Mei-Zhi; Zhang, Peng; Xia, Kun; Tang, Bei-Sha; Shen, Lu

    2013-07-01

    Genetic heterogeneity is common in many Mendelian disorders such as hereditary spastic paraplegia (HSP), which makes the genetic diagnosis more complicated. The goal of this study was to investigate a Chinese family with recessive hereditary spastic paraplegia, of which causative mutations could not be identified using the conventional PCR-based direct sequencing. Next-generation sequencing of all the transcripts of whole genome exome, after on-array hybrid capture, was performed on two affected male subjects (the proband and his brother). A missense mutation (c.1661G>A, p.R554H) was identified in ABCD1. Subsequently, PCR-based direct sequencing of other family members revealed that the mutation was co-segregating with the disease, indicating that ABCD1 mutation was the pathogenic event for this family. Very long-chain fatty acids (VLCFA) assay in the two affected cases confirmed X-ALD. Our study suggests exome sequencing can be used not only to find a novel causative gene, but also to quickly identify mutations of known genes when the clinical elements are etiologically misleading. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population.

    Science.gov (United States)

    Rosenberg, Thomas; Nørby, Søren; Schwartz, Marianne; Saillard, Juliette; Magalhães, Paulo J; Leroy, David; Kann, Erik C; Duno, Morten

    2016-03-01

    In Denmark, the occurrence of Leber hereditary optic neuropathy (LHON) has continuously been monitored since 1944. We provide here a summary of 70 years of data collection including registered lines and subjects by the end of 2012. Affected individuals were identified from a national register of hereditary eye diseases at the National Eye Clinic (NEC), a tertiary low vision rehabilitation center for the entire Danish population. The assembling of LHON pedigrees was based on the reconstruction of published families and newly diagnosed cases from 1980 to 2012 identified in the files of NEC. Genealogic follow-up on the maternal ancestry of all affected individuals was performed to identify a possible relation to an already known maternal line. A full genotypic characterization of the nation-based LHON cohort is provided. Forty different lines were identified. The number of live affected individuals with a verified mitochondrial DNA mutation was 104 on January 1, 2013, which translates to a prevalence rate of 1:54,000 in the Danish population. Haplogroup distribution as well as mutational spectrum of the Danish LHON cohort do not deviate from those of other European populations. The genealogic follow-up reveals a relatively high turnover among families with approximately 15 newly affected families per century and the dying out of earlier maternal lines.

  10. Knowledge about breast cancer and hereditary breast cancer among nurses in a public hospital

    Directory of Open Access Journals (Sweden)

    Carmen Maria Dornelles Prolla

    2015-02-01

    Full Text Available OBJECTIVE: To assess the knowledge of nurses involved in the care of oncology patients in a public university hospital, regarding breast cancer and hereditary breast cancer, and to verify the use of such knowledge in their daily practice.METHODS: This is a descriptive cross-sectional study. Data were obtained through a structured, self-administered questionnaire. Out of 154 nurses, 137 (88.9% agreed to participate in the study. Two questionnaires were excluded such that 135 questionnaires were analyzed.RESULTS: The global percentage of correct answers was not associated with age (p=0.173 or degree/specialization (p=0.815. Questions were classified into categories. In categories involving knowledge of established breast cancer risk factors and indicators of hereditary breast cancer, the rate of correct answers was 65.8% and 66.4%, respectively. On the practice of genetic counseling, 40.7% of those interviewed were not sure about the definition of genetic counseling and 78.5% reported never having identified or referred a patient at genetic risk for specialized risk assessment. Practice of educational actions regarding this subject was reported by 48.5% of those interviewed.CONCLUSION: This study reinforces the need to develop qualifying actions for nurses, so that strategies to control breast cancer become effective in their health care practice.

  11. Organization and Running of the First Comprehensive Hereditary Cancer Clinic in India

    Directory of Open Access Journals (Sweden)

    Rajkumar T

    2005-11-01

    Full Text Available Abstract Hereditary cancers are thought to account for around 5% of cancers, particularly breast/ovarian and colorectal cancers. In India there is a paucity of data on hereditary cancers and the mutations in some of the common genes linked to hereditary cancers, such as BRCA1, BRCA2, hMSH2 and hMLH1. The country's first comprehensive hereditary cancer clinic was established in February 2002. The article describes the organization and running of the Clinic. It also discusses some of the social issues relevant to the given population in running the Hereditary Cancer Clinic.

  12. A CASE OF PERSISTANT INTRACRANIAL HYPERTENSION IN A 7 YEARS OLD GIRL WITH MULTIPLE HEREDITARY EXOSTOSIS AND CRANIOSTENOSIS

    Directory of Open Access Journals (Sweden)

    L.M. Kuzenkova

    2007-01-01

    Full Text Available The article demonstrates a case of rare hereditary syndrome observation — with the multiple hereditary exostosis (MHE syndrome in a 7 years old girl. The article covers hereditary and clinical features and life prognosis of the syndrome.Key words: intracranial hypertension, multiple hereditary exostosis (MHE syndrome, craniostenosis, children.

  13. 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.

    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

  14. Dementia with non-hereditary cystatin C angiopathy

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Blöndal, H; Jóhannesson, G

    1989-01-01

    Brain biopsies from two patients with non-hereditary cerebral hemorrhages and eighty autopsied cases with the clinical diagnosis of dementia are presented. The biopsied cases, both males aged 64 and 59, had a sudden onset of cerebral hemorrhage, mild progressive dementia and cystatin C cerebral...

  15. 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…

  16. REVIEW ARTICLE Therapeutic avenues for hereditary forms of ...

    Indian Academy of Sciences (India)

    chitra

    Key words: retinal disease; retinitis pigmentosa; gene therapy; retinoid; clinical trial; stem cell; cell therapy. Abstract. Hereditary retinal diseases, known as retinal degenerations or dystrophies, are a large group of inherited eye disorders resulting in irreversible visual loss and blindness. They develop due to mutations in one ...

  17. 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 ...

  18. 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.

  19. Report of hereditary gingival fibromatosis in two Nigerian siblings ...

    African Journals Online (AJOL)

    Background: Hereditary Gingival Fibromatosis (HGF) is a rare condition with a prevalence of 1:750,000, and can present as an isolated disorder or more rarely as a syndrome component. It is characterised by a slow and progressive enlargement of both maxillary and mandibular 28rganiza with varying severity between ...

  20. Genetics Home Reference: infantile-onset ascending hereditary spastic paralysis

    Science.gov (United States)

    ... characterized by progressive muscle stiffness (spasticity) and eventual paralysis of the lower limbs (paraplegia). The spasticity and paraplegia result from degeneration (atrophy) of motor neurons , which are specialized nerve cells in the brain and spinal cord that control muscle movement. Hereditary ...

  1. 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

  2. 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…

  3. Managing oral bleeding in children with hereditary bleeding disorders

    African Journals Online (AJOL)

    The prevention of traumatic and infective dental conditions is an important part of oral health care in individuals with hereditary bleeding disorders. This would reduce the need for treatment and should reduce the number of emergency visits. Key words: Haemophilia, von Willebrand disease, gingival bleeding, dental ...

  4. Progressive cerebellar atrophy: hereditary ataxias and disorders with spinocerebellar degeneration

    NARCIS (Netherlands)

    Wolf, N.I.; Koenig, M.; Dulac, O.L.M.; Sarnat, H.B.

    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

  5. RECRUITMENT OF PATIENTS WITH HEREDITARY HAEMOCHROMATOSIS AS BLOOD DONORS

    Directory of Open Access Journals (Sweden)

    Marko Cukjati

    2004-12-01

    Full Text Available Background. Hereditary haemochromatosis is the most common inherited disorder in white persons with prevalence of about 1 in 200. Therapeutic phlebotomy is an effective treatment for the disease and prevents its sequele. In addition to their altruism, patients with hereditary haemochromatosis have also medical and monetary incentives for blood donation. Current guidelines do not allow haemochromatosis patients to donate blood. About two thirds of patients are eligible as blood donors and about two thirds of therapeutically drawn blood is suitable for transfusion. Therapeutically drawn blood could increase the blood supply by 1.5 to 30%.Conclusions. The number of states that already accept patients with hereditary haemochromatosis as blood donors is increasing. To avoid monetary incentives they offer free phlebotomies for all patients with hereditary haemochromatosis. There have been no reports about higher incidence of transfusion reactions. In Slovenia the number of therapeutic phlebotomy is increasing. We should evaluate the possibilities for recruitment of haemochromatosis patients as blood donors also in our country. It is necessary to modify regulatory restrictions and to ensure that there is no other incentives than altruism for blood donation.

  6. 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

  7. 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...

  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. Hereditary gingival fibromatosis: report of family case series ...

    African Journals Online (AJOL)

    Hereditary gingival hyperplasia (HGF) is a rare condition characterised by hyperplastic, dense fibrous connective tissue with acanthotic gingival epithelium. A family presented at the School of Dental Sciences, University of Nairobi with a complaint that some of the children developed swollen gums very early in life and that ...

  10. Hereditary primary open angle glaucoma: case study of a Nigerian ...

    African Journals Online (AJOL)

    Objective: To present a case of hereditary primary open angle glaucoma in a Nigerian family. Method: Six members of an Ibo family from Delta State, Nigeria were interviewed and examined by the authors. Information on age, gender, tribe, history of blindness, eye disease and other medical conditions was recorded.

  11. Hereditary atypical retinitis pigmentosa: case report | Omoti | Annals ...

    African Journals Online (AJOL)

    This report presents four generations of hereditary atypical (pericentric) retinitis pigmentosa in an Itsekiri family of Warri, Delta state of Nigeria. The patients presented with nyctalopia, waxy disc pallor, arteriolar attenuation, pigment deposits around the optic nerve and visual field loss. The cases were typically mild with ...

  12. 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...

  13. Mutations in TITF-1 are associated with benign hereditary chorea

    NARCIS (Netherlands)

    G.J. Breedveld (Guido); A. Guala (Andrea); B.A. Oostra (Ben); A.K. Percy; L.S. Dure; P. Harper; W.F.M. Arts (Willem Frans); L.P. Lazarou; H. van der Linde; B.B.A. de Vries (Bert); M. Joosse (Marijke); M.E. MacDonald; H. Krude; A. Grüters (Annette); J.W.F. van Dongen (Jeroen); C. Danesino (Cesare); P. Heutink (Peter)

    2002-01-01

    textabstractBenign hereditary chorea (BHC) (MIM 118700) is an autosomal dominant movement disorder. The early onset of symptoms (usually before the age of 5 years) and the observation that in some BHC families the symptoms tend to decrease in adulthood suggests that the disorder

  14. Mutations in TITF-1 are associated with benign hereditary chorea

    NARCIS (Netherlands)

    Breedveld, GJ; van Dongen, JWF; Danesino, C; Guala, A; Percy, AK; Dure, LS; Harper, P; Lazarou, LP; van der Linde, H; Joosse, M; Gruters, A; MacDonald, ME; de Vries, BBA; Arts, WFM; Oostra, BA; Krude, H; Heutink, P

    2002-01-01

    Benign hereditary chorea (BHC) (MIM 118700) is an autosomal dominant movement disorder. The early onset of symptoms (usually before the age of 5 years) and the observation that in some BHC families the symptoms tend to decrease in adulthood suggests that the disorder results from a developmental

  15. Mutations in TITF-1 are associated with benign hereditary chorea.

    NARCIS (Netherlands)

    Breedveld, G.J.; Dongen, J.W. van; Danesino, C.; Guala, A.; Percy, A.K.; Dure, L.S.; Harper, P.; Lazarou, L.P.; Linde, H. van der; Joosse, M.; Gruters, A.; MacDonald, M.E.; Vries, L.B.A. de; Arts, P.J.W.; Oostra, B.A.; Krude, H.; Heutink, P.

    2002-01-01

    Benign hereditary chorea (BHC) (MIM 118700) is an autosomal dominant movement disorder. The early onset of symptoms (usually before the age of 5 years) and the observation that in some BHC families the symptoms tend to decrease in adulthood suggests that the disorder results from a developmental

  16. Genetics Home Reference: hereditary sensory neuropathy type IA

    Science.gov (United States)

    ... hereditary sensory neuropathy type IA typically get open sores (ulcers) on their feet or hands or infections of the soft tissue of the fingertips (whitlows) that are slow to heal. Because affected ... of these sores, they may not seek immediate treatment. Without treatment, ...

  17. 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.

  18. Hereditary ovarian cancer: not only BRCA 1 and 2 genes.

    Science.gov (United States)

    Toss, Angela; Tomasello, Chiara; Razzaboni, Elisabetta; Contu, Giannina; Grandi, Giovanni; Cagnacci, Angelo; Schilder, Russell J; Cortesi, Laura

    2015-01-01

    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.

  19. 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

  20. RB1 mutations and second primary malignancies after hereditary retinoblastoma

    NARCIS (Netherlands)

    Dommering, Charlotte J.; Marees, Tamara; van der Hout, Annemarie H.; Imhof, Saskia M.; Meijers-Heijboer, Hanne; Ringens, Peter J.; van Leeuwen, Flora E.; Moll, Annette C.

    Survivors of hereditary retinoblastoma have a high risk of second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater risk of second primary malignancies in a large cohort. We conducted a retrospective cohort study of 199

  1. RB1 mutations and second primary malignancies after hereditary retinoblastoma

    NARCIS (Netherlands)

    Dommering, Charlotte J.; Marees, Tamara; van der Hout, Annemarie H.; Imhof, Saskia M.; Meijers-Heijboer, Hanne; Ringens, Peter J.; van Leeuwen, Flora E.; Moll, Annette C.

    2012-01-01

    Survivors of hereditary retinoblastoma have a high risk of second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater risk of second primary malignancies in a large cohort. We conducted a retrospective cohort study of 199

  2. On the many faces of Leber hereditary optic neuropathy

    NARCIS (Netherlands)

    Oostra, R. J.; Tijmes, N. T.; Cobben, J. M.; Bolhuis, P. A.; van Nesselrooij, B. P.; Houtman, W. A.; de Kok-Nazaruk, M. M.; Bleeker-Wagemakers, E. M.

    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

  3. 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.

  4. 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

  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

  6. Hereditary hemochromatosis: genetic complexity and new diagnostic approaches.

    NARCIS (Netherlands)

    Swinkels, D.W.; Janssen, M.C.H.; Bergmans, J.; Marx, J.J.M.

    2006-01-01

    Since the discovery of the hemochromatosis gene (HFE) in 1996, several novel gene defects have been detected, explaining the mechanism and diversity of iron-overload diseases. At least 4 main types of hereditary hemochromatosis (HH) have been identified. Surprisingly, genes involved in HH encode for

  7. [Intrathecal baclofen in hereditary spastic paraparesis: benefits and limitations].

    Science.gov (United States)

    Lambrecq, V; Muller, F; Joseph, P-A; Cuny, E; Mazaux, J-M; Barat, M

    2007-10-01

    Chronic intrathecal delivery of baclofen has been introduced for treatment of severe spinal spasticity. Very little is known about this treatment in hereditary spastic paraparesis. Here we review the benefits and limitations of pump implantation for baclofen delivery in this population. Consecutive patients presenting with hereditary spastic paraparesis were assessed for spasticity (Ashworth and Penn scores), muscular strength and walking (speed, comfort and perimeter length). The effect of intrathecal delivery of baclofen was judged after progressive bolus injections or chronic administration by electrical syringe. The pump implantation was proposed when spasticity scores decreased by 2 or more points, with muscular strength preserved and walking area increased. We investigated 6 patients (3 males; mean age 48 years) with hereditary spastic paraparesis. The mean follow-up was 19 years; for 4 patients who received pump implantation, the mean follow-up was 6.2 years. The mean baclofen daily dose was 75 mug. Satisfaction was high for patients who received implantation early instead of waiting for the natural course of the disease. Some patients with hereditary spastic paraparesis have good functional improvement with chronic intrathecal delivery of baclofen if walking is still possible. Despite the natural history of the disease, functional results are stable during the first 5 years of treatment. The data indicate a possible compromise between decreased spasticity and muscular strengthening with the treatment.

  8. 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....

  9. 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

  10. 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

  11. Hereditary family signature of facial expression.

    Science.gov (United States)

    Peleg, Gili; Katzir, Gadi; Peleg, Ofer; Kamara, Michal; Brodsky, Leonid; Hel-Or, Hagit; Keren, Daniel; Nevo, Eviatar

    2006-10-24

    Although facial expressions of emotion are universal, individual differences create a facial expression "signature" for each person; but, is there a unique family facial expression signature? Only a few family studies on the heredity of facial expressions have been performed, none of which compared the gestalt of movements in various emotional states; they compared only a few movements in one or two emotional states. No studies, to our knowledge, have compared movements of congenitally blind subjects with their relatives to our knowledge. Using two types of analyses, we show a correlation between movements of congenitally blind subjects with those of their relatives in think-concentrate, sadness, anger, disgust, joy, and surprise and provide evidence for a unique family facial expression signature. In the analysis "in-out family test," a particular movement was compared each time across subjects. Results show that the frequency of occurrence of a movement of a congenitally blind subject in his family is significantly higher than that outside of his family in think-concentrate, sadness, and anger. In the analysis "the classification test," in which congenitally blind subjects were classified to their families according to the gestalt of movements, results show 80% correct classification over the entire interview and 75% in anger. Analysis of the movements' frequencies in anger revealed a correlation between the movements' frequencies of congenitally blind individuals and those of their relatives. This study anticipates discovering genes that influence facial expressions, understanding their evolutionary significance, and elucidating repair mechanisms for syndromes lacking facial expression, such as autism.

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

    Science.gov (United States)

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

    2006-08-07

    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. 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. 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. 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.

  13. [Frequency of hereditary neurologic diseases. A clinical study].

    Science.gov (United States)

    Leone, M; Baldini, S; Voltolin, G; Norat, M; Bottacchi, E

    1993-09-01

    The nervous system is affected in 30% of hereditary monogenic disorders and as many as 500 single-gene disorders display major neurologic symptoms. We have studied the frequency of hereditary neurological diseases to assess their importance in daily hospital activity. Only single-gene hereditary diseases with central or peripheral nervous system involvement were considered; thus chromosomal diseases and diseases with multifactorial etiology were excluded. We surveyed admission to in- and out-patient departments of Neurology, Pediatrics, and Dermatology of the Aosta Regional Hospital for the calendar years 1982-1991, collecting 229 cases, 95 women and 134 men. Out-patient departments held 126 patients, the others came from in-patient departments. Admission to the neurological in-patient department were 1.8% of total neurological admissions in the same period. Each diagnosis was assigned to the code number of the International Classification of Diseases (ICD-IX Revision, 1975). We found 33 different phenotypes. Most frequent diagnoses were: essential tremor (89 patients), hereditary sensory-motor neuropathy (HSMN) type I (28), Huntington's chorea (13), progressive muscular dystrophy limb-girdle type (8), neurofibromatosis type I (9), HSMN type II (9), spinocerebellar ataxia (9), hereditary spastic paraplegia (7), spinal muscular atrophy type IV (5), myotonic dystrophy (5), cerebellar ataxia (4), HSMN type III (4), spinal muscular atrophy type II and III (3), tuberous sclerosis (3). Essential tremor mostly affected persons in the over-50 age groups. On the contrary, the other neurologic monogenic diseases were diagnosed in all ages with the following age-group breakdown: 0-9, 11%; 10-19, 16%; 20-29, 15%; 30-39, 8%; 40-49, 11%; 50-59, 19%; 60-69, 14%, 70+, 7%. Consistently with the general rule, autosomic recessive diseases have the earliest onset and autosomic dominant ones the latest; HSMN, spinal muscular atrophy and Huntington's chorea were the disorders diagnosed

  14. Prevalence and impact of founder mutations in hereditary breast cancer in Latin America

    Directory of Open Access Journals (Sweden)

    Patricia Ashton-Prolla

    2014-01-01

    Full Text Available Approximately 10% of all cancers are considered hereditary and are primarily caused by germline, high penetrance mutations in cancer predisposition genes. Although most cancer predisposition genes are considered molecularly heterogeneous, displaying hundreds of different disease-causing sequence alterations, founder mutations have been identified in certain populations. In some Latin American countries, founder mutations associated with increased risk of breast and other cancers have been described. This is particularly interesting considering that in most of these countries, populations are highly admixed with genetic contributions from native populations and from the influx of several distinct populations of immigrants. In this article, we present a review of the scientific literature on the subject and describe current data available on founder mutations described in the most common breast cancer predisposition genes: BRCA1, BRCA2 and TP53.

  15. Next generation sequencing for molecular confirmation of hereditary sudden cardiac death syndromes.

    Science.gov (United States)

    Márquez, Manlio F; Cruz-Robles, David; Ines-Real, Selene; Vargas-Alarcón, Gilberto; Cárdenas, Manuel

    2015-01-01

    Hereditary sudden cardiac death syndromes comprise a wide range of diseases resulting from alteration in cardiac ion channels. Genes involved in these syndromes represent diverse mutations that cause the altered encoding of the diverse proteins constituting these channels, thus affecting directly the currents of the corresponding ions. In the present article we will briefly review how to arrive to a clinical diagnosis and we will present the results of molecular genetic studies made in Mexican subjects attending the SCD Syndromes Clinic of the National Institute of Cardiology of Mexico City. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  16. Reduced regional cerebral blood flow in SPG4-linked hereditary spastic paraplegia

    DEFF Research Database (Denmark)

    Scheuer, Kristin H; Nielsen, Jørgen E; Krabbe, Katja

    2005-01-01

    Hereditary spastic paraplegia (HSP) linked to the spastic gait gene 4 (SPG4) is controversial, as the "pure" form traditionally has been considered confined to the long axons of the spinal cord. However, recent immunolabeling experiments have demonstrated extensive Spastin expression in the cortex...... and striatum. This could indicate a more widespread neuropathology from mutations in the SPG4 gene than previously assumed. The aim of this study was therefore to ascertain the extent of cerebral involvement in SPG4 linked HSP by neuropsychological examination and measurement of the regional cerebral blood...... flow (rCBF) as an indirect marker of regional neuronal activity. Eighteen SPG4 patients and 18 matched control subjects were studied. Resting state rCBF was measured using Positron Emission Tomography (PET) and the (15)O-labelled water bolus technique and relative group differences were explored using...

  17. Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population

    DEFF Research Database (Denmark)

    Rosenberg, Niels Thomas; Nørby, Søren; Schwartz, Marianne

    2016-01-01

    in the files of NEC. Genealogic follow-up on the maternal ancestry of all affected individuals was performed to identify a possible relation to an already known maternal line. A full genotypic characterization of the nation-based LHON cohort is provided. RESULTS: Forty different lines were identified......PURPOSE: In Denmark, the occurrence of Leber hereditary optic neuropathy (LHON) has continuously been monitored since 1944. We provide here a summary of 70 years of data collection including registered lines and subjects by the end of 2012. METHODS: Affected individuals were identified from....... The number of live affected individuals with a verified mitochondrial DNA mutation was 104 on January 1, 2013, which translates to a prevalence rate of 1:54,000 in the Danish population. CONCLUSIONS: Haplogroup distribution as well as mutational spectrum of the Danish LHON cohort do not deviate from those...

  18. 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

    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

  19. Determinants of angiotensin-converting enzyme inhibitor (ACEI) intolerance and angioedema in the UK Clinical Practice Research Datalink.

    Science.gov (United States)

    Mahmoudpour, Seyed Hamidreza; Baranova, Ekaterina Vitalievna; Souverein, Patrick C; Asselbergs, Folkert W; de Boer, Anthonius; Maitland-van der Zee, Anke Hilse

    2016-12-01

    The aim of the present study was to describe the occurrence and determinants of angiotensin-converting enzyme (ACE) inhibitor (ACEI) intolerance and angioedema (AE) among patients initiating ACEI therapy in a real-world primary care population. Two nested case-control studies were conducted in a cohort of 276 977 patients aged ≥45 years initiating ACEIs from 2007 to 2014 in the UK Clinical Practice Research Datalink (CPRD). Cases of AE occurring for the first time during ACEI therapy (n = 416) were matched with AE-free controls (n = 4335) on the duration of ACEI treatment. Documented switches to angiotensin-II receptor blockers in the prescription records were used to identify ACEI-intolerance cases (n = 24 709), and these were matched with continuous ACEI users (n = 84 238) on the duration of ACEI therapy. Conditional logistic regression was used to assess the associations of demographic factors, comorbidities and comedication with AE and ACEI intolerance. AE during ACEI therapy was associated with age over 65 years [odds ratio (OR) 1.36, 95% confidence interval (CI) 1.07, 1.73], history of allergy (OR 1.53, 95% CI 1.19, 1.96), use of calcium channel blockers (OR 1.57, 95% CI 1.23; 2.01), use of antihistamines (OR 21.25, 95% CI 16.44, 27.46) and use of systemic corticosteroids (OR 4.52, 95% CI 3.26, 6.27). ACEI intolerance was significantly associated with more comorbidities and comedication compared with AE, including allergy (OR 2.02, 95% CI 1.96, 2.09), use of antiasthmatic drugs (OR 1.51, 95% CI 1.42, 1.61) and use of antihistamines (OR 1.53, 95% CI 1.43, 1.63). Among ACEI users developing AE or ACEI intolerance, several comorbidities and comedication classes were significantly more prevalent compared with ACEI users not developing these adverse reactions. © 2016 The British Pharmacological Society.

  20. 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

  1. Novel EXOSC3 mutation causes complicated hereditary spastic paraplegia.

    Science.gov (United States)

    Halevy, Ayelet; Lerer, Israela; Cohen, Rony; Kornreich, Liora; Shuper, Avinoam; Gamliel, Moria; Zimerman, Bat-El; Korabi, Isam; Meiner, Vardiella; Straussberg, Rachel; Lossos, Alexander

    2014-11-01

    We describe two pairs of siblings from a consanguineous family manifesting autosomal recessive hereditary spastic paraplegia caused by a novel mutation in the EXOSC3 gene, previously reported in pontocerebellar hypoplasia type 1. Clinical findings included delayed motor milestones, early-onset spastic paraplegia, variable cognitive disability, and cerebellar signs. Cerebral imaging demonstrated enlarged cisterna magna and mild hypoplasia and atrophy of the lower vermis with a normal pons. Genetic analysis using homozygosity mapping followed by whole exome sequencing identified homozygous c.571G>T; p.G191C mutation in the EXOSC3 gene. We suggest that EXOSC3 mutations may present not only as pontocerebellar hypoplasia type 1, but also as a complicated form of hereditary spastic paraplegia without pontine hypoplasia or atrophy.

  2. Genetics and Genetic Testing in Hereditary Colorectal Cancer.

    Science.gov (United States)

    Stoffel, Elena M; Boland, C Richard

    2015-10-01

    Colorectal cancer (CRC) remains the third most common cancer affecting men and women in the United States. Approximately one-third of CRCs are diagnosed in individuals who have family members also affected with the disease. Although the vast majority of colorectal neoplasms develop as a consequence of somatic genomic alterations arising in individual cells, approximately 5% of all CRCs arise in the setting of germline mutations in genes involved in key cellular processes. To date, multiple genes have been implicated in single-gene hereditary cancer syndromes, many of which are associated with increased risk for CRC, as well as other tumor types. This review outlines the clinical, pathologic, and genetic features of the hereditary cancer syndromes known to be associated with increased risk for CRC and delineates strategies for implementing genetic risk assessments in clinical settings. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  3. Working the endless puzzle of hereditary autoinflammatory disorders.

    Science.gov (United States)

    Caso, Francesco; Cantarini, Luca; Lucherini, Orso Maria; Sfriso, Paolo; Fioretti, Maria; Costa, Luisa; Vitale, Antonio; Atteno, Mariangela; Galeazzi, Mauro; Muscari, Isabella; Magnotti, Flora; Frediani, Bruno; Punzi, Leonardo; Rigante, Donato

    2014-05-01

    Hereditary autoinflammatory disorders encompass manifold dysfunctions of innate immunity caused by mutations in genes coding for the main characters of the inflammatory scene: most of these conditions have an early onset, ranging from the first days of life to the first decades, and include hereditary periodic fevers, NLRP-related diseases, granulomatous and pyogenic syndromes, which are basically characterized by upturned inflammasome activity and overproduction of bioactive interleukin (IL)-1β and other proinflammatory cytokines. The discovery of a causative link between autoinflammation and IL-1β release has improved our understanding of the intimate mechanisms of innate immunity, and has likewise led to the identification of extraordinary treatments for many of these disorders.

  4. Hereditary Hemorrhagic Telangiectasia: A Primer for Critical Care Nurses.

    Science.gov (United States)

    Sacco, Kathleen M; Barkley, Thomas W

    2016-06-01

    Hereditary hemorrhagic telangiectasia is a rare, autosomal dominant genetic disease that causes abnormal growth of blood vessels and, subsequently, life-threatening arteriovenous malformations in vital organs. Epistaxis may be one of the initial clues that a patient has more serious, generalized arteriovenous malformations. Recommended treatment involves careful evaluation to determine the severity and risk of spontaneous rupture of the malformations and the management of various signs and symptoms. The disease remains undiagnosed in many patients, and health care providers may miss the diagnosis until catastrophic events happen in multiple family members. Prompt recognition of hereditary hemorrhagic telangiectasia and early intervention can halt the dangerous course of the disease. Critical care nurses can assist with early diagnosis within families with this genetic disease, thus preventing early death and disability. ©2016 American Association of Critical-Care Nurses.

  5. Management of Hereditary Breast and Ovarian Cancer. The Asian Experience

    Directory of Open Access Journals (Sweden)

    Ava Kwong

    2017-02-01

    Full Text Available BRCA1/BRCA2 mutations are the most common high penetrant genes associated with an increased lifetime risk for hereditary breast and ovarian cancer (HBOC. Although genetic testing is standard of care in Western developed countries, there are still variations in availability of genetic testing and risk assessment for HBOC in Asia. Depending on the countries, there are variations in the clinical strategies and cancer management. The Asian BRCA Consortium has grouped together 14 Asian countries and reviewed genetic counselling/testing uptake rates and clinical management options in these countries. Moreover economic factors, healthcare and legal frameworks, and cultural issues affecting the genetic service availability in Asia were discussed. Mutation spectrum, and VUS rates and the increase use of NGS gene panel testing poses more decisional issues in the clinical management of Hereditary Breast cancer in Asia. These will be discussed. Keywords: BRCA1/BRCA2, germline, HBOC, Asia BRCA Consortium, NGS

  6. CLINICAL AND MORPHOLOGICAL FEATURES OF HEREDITARY OVARIAN CANCER

    Directory of Open Access Journals (Sweden)

    K. B. Kotiv

    2017-01-01

    Full Text Available Germ-line mutations in BRCA1 and BRCA2 genes are the most established risk factors for hereditary breast and ovarian cancers. The purpose of the study was to analyze BRCA1/2 testing in ovarian cancer patients. Materials and methods. We analyzed 222 patients with ovarian cancer (OC who underwent genetic testing. Results. Recurrent Slavic mutations in these genes were detected in 60/222 (27% patients.104 patients lacked any clinical signs of hereditary form of the disease, however BRCA1/2 genetic defects were identified among 11 (11% of these women. BRCA1/2-associated carcinomas were characterized by more advanced stage at diagnosis and predominance of high-grade serous histological tumor subtype. Conclusion. These results emphasize the need for BRCA1/2 testing for all patients with OC. BRCA1/2-associated carcinomas have clinical and pathological cgaracteristics, which should be considered while planning therapy. 

  7. [An aged case of hereditary xanthinuria with xanthine urinary calculi].

    Science.gov (United States)

    Kario, K; Matsuo, T; Nakao, K

    1991-01-01

    A 74-year-old female with hereditary xanthinuria and xanthine stones is reported. She has a family history of consanguineous parents and a past history of right side nephrectomy due to a xanthine renal stone and vesicolithotomy of 3 bladder stones approximately 5 X 4 X 4 cm in size at the age of 58 and 71, respectively. Her young brother exhibited a slightly elevated urinary excretion of oxypurines. Laboratory examination showed a low serum level (0.3 mg/dl) and urinary excretion (1.56 mg/day) of uric acid, and high plasma and urine levels of oxypurines. No xanthine oxidase activity was detectably in duodenal mucosa by biopsy specimen obtained by duodenofiberscopy. Now she has another stone approximately 5 X 4 X 4 cm in her bladder. There have been are few elderly cases of hereditary xanthinuria with recurrent giant urolithiasis.

  8. 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?

  9. Hereditary Renal Cystic Disorders: Imaging of the Kidneys and Beyond.

    Science.gov (United States)

    Dillman, Jonathan R; Trout, Andrew T; Smith, Ethan A; Towbin, Alexander J

    2017-01-01

    The purpose of this article is to review the hereditary renal cystic diseases that can manifest in children and adults, with specific attention to pathogenesis and imaging features. Various common and uncommon hereditary renal cystic diseases are reviewed in terms of their underlying etiology, including the involved genetic mutations and the affected proteins and cellular structures. Focus is placed on the morphologic findings in each condition and the features that distinguish one disorder from another. The two most common categories of hereditary renal cystic disease are (a) the ciliopathic disorders, which are related to mutations affecting the primary cilia (called "ciliopathies"), and (b) the phakomatoses. Autosomal dominant polycystic kidney disease, autosomal recessive polycystic kidney disease, and the "medullary cystic disease complex" are all ciliopathies but have different phenotypes. Tuberous sclerosis complex and the associated "contiguous gene syndrome," as well as von Hippel-Lindau syndrome, are phakomatoses that can manifest with cystic renal lesions but have uniquely different extrarenal manifestations. Finally, DICER1 mutations can manifest with renal cystic lesions (typically, cystic nephromas) in patients predisposed to other malignancies in the chest, ovaries, and thyroid. Although some overlap exists in the appearance of the renal cysts associated with each of these diseases, there are clear morphologic differences (eg, cyst size, location, and complexity) that are emphasized in this review. To improve patient outcomes, it is important for the radiologist to recognize the various hereditary renal cystic diseases so that a correct diagnosis is assigned and so that the patient is adequately evaluated and followed up. ©RSNA, 2017.

  10. Blood pressure follows the kidney: Perinatal influences on hereditary hypertension

    OpenAIRE

    Koeners, Maarten P; Braam, Branko; Joles, Jaap A

    2008-01-01

    Epidemiological and experimental data strongly suggest that cardiovascular diseases can originate from an aberrant environment during fetal development, a phenomenon referred to as perinatal programming. This review will focus on the role of the kidneys in determining blood pressure, and how (re)programming the renal development can persistently ameliorate hereditary hypertension. By combining physiologic and genomic studies we have discovered some candidate pathways suited for (re)programmin...

  11. 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.

  12. 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....... No definite symptoms in the female carriers could be ascribed to the mutation. These data suggest the pathology to be an underlying dysmyelinating disorder in combination with a central axonal degeneration....

  13. The diagnostic quandary of hereditary haemorrhagic telangiectasia vs. CREST syndrome.

    Science.gov (United States)

    Lee, J B; Ben-Aviv, D; Covello, S P

    2001-10-01

    The distribution and clinical appearance of the telangiectasia in the CREST syndrome (calcinosis, Raynaud's phenomenon, oesophageal involvement, sclerodactyly, telangiectasia) and hereditary haemorrhagic telangiectasia (HHT) are very similar. Several previously reported cases of the CREST syndrome simulating HHT illustrate this diagnostic quandary. We report a patient who met the diagnostic criteria for both the CREST syndrome and HHT, and discuss the distinguishing features of the two diseases, including the distinctive histopathological findings of telangiectasia in HHT.

  14. 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. © International & American Associations for

  15. 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.)

  16. Increased insulin secretory capacity but decreased insulin sensitivity after correction of iron overload by phlebotomy in hereditary haemochromatosis.

    Science.gov (United States)

    Abraham, D; Rogers, J; Gault, P; Kushner, J P; McClain, D A

    2006-11-01

    We recently demonstrated that humans with hereditary haemochromatosis have decreased insulin secretory capacity with a compensatory increase in insulin sensitivity. We therefore determined how these measures change after correction of tissue iron overload. Five non-diabetic subjects who had been studied previously at the time of initial diagnosis by means of the OGTT and frequently sampled intravenous glucose tolerance tests (FSIVGTT) underwent phlebotomy to normalise their serum ferritin. After normalisation of ferritin they were studied again (33+/-4 months after the initial studies) by OGTT and FSIVGTT. Normalisation of tissue iron stores resulted in an average 1.8-fold increase in the integrated area under the insulin curve during OGTT (pdisposition index (AIRgxSi) was unchanged (5% increase, p=0.90). BMI and fasting glucose were unchanged. At the time of diagnosis of haemochromatosis, four of the subjects had IGT. After normalisation of ferritin, two achieved NGT and two remained with IGT, despite 2.5- and 3.7-fold increases in insulin secretory capacity. Insulin secretory capacity improves after normalisation of iron stores in subjects with hereditary haemochromatosis. Glucose tolerance status improves incompletely because of decreased insulin sensitivity after phlebotomy. We conclude that tissue iron levels are an important determinant of insulin secretion and insulin action.

  17. Expanding subjectivities

    DEFF Research Database (Denmark)

    Lundgaard Andersen, Linda; Soldz, Stephen

    2012-01-01

    A major theme in recent psychoanalytic thinking concerns the use of therapist subjectivity, especially “countertransference,” in understanding patients. This thinking converges with and expands developments in qualitative research regarding the use of researcher subjectivity as a tool to understa...

  18. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Hereditary myopathies with early respiratory insufficiency in adults.

    Science.gov (United States)

    Naddaf, Elie; Milone, Margherita

    2017-11-01

    Hereditary myopathies with early respiratory insufficiency as a predominant feature of the clinical phenotype are uncommon and underestimated in adults. We reviewed the clinical and laboratory data of patients with hereditary myopathies who demonstrated early respiratory insufficiency before the need for ambulatory assistance. Only patients with disease-causing mutations or a specific histopathological diagnosis were included. Patients with cardiomyopathy were excluded. We identified 22 patients; half had isolated respiratory symptoms at onset. The diagnosis of the myopathy was often delayed, resulting in delayed ventilatory support. The most common myopathies were adult-onset Pompe disease, myofibrillar myopathy, multi-minicore disease, and myotonic dystrophy type 1. Single cases of laminopathy, MELAS (mitochondrial encephalomyopathy with lactic acidosis and strokelike events), centronuclear myopathy, and cytoplasmic body myopathy were identified. We highlighted the most common hereditary myopathies associated with early respiratory insufficiency as the predominant clinical feature, and underscored the importance of a timely diagnosis for patient care. Muscle Nerve 56: 881-886, 2017. © 2017 Wiley Periodicals, Inc.

  20. Practice Bulletin No 182: Hereditary Breast and Ovarian Cancer Syndrome.

    Science.gov (United States)

    2017-09-01

    Hereditary breast and ovarian cancer syndrome is an inherited cancer-susceptibility syndrome characterized by multiple family members with breast cancer, ovarian cancer, or both. Based on the contemporary understanding of the origins and management of ovarian cancer and for simplicity in this document, ovarian cancer also refers to fallopian tube cancer and primary peritoneal cancer. Clinical genetic testing for gene mutations allows more precise identification of those women who are at an increased risk of inherited breast cancer and ovarian cancer. For these individuals, screening and prevention strategies can be instituted to reduce their risks. Obstetrician-gynecologists play an important role in the identification and management of women with hereditary breast and ovarian cancer syndrome. If an obstetrician-gynecologist or other gynecologic care provider does not have the necessary knowledge or expertise in cancer genetics to counsel a patient appropriately, referral to a genetic counselor, gynecologic or medical oncologist, or other genetics specialist should be considered (1). More genes are being discovered that impart varying risks of breast cancer, ovarian cancer, and other types of cancer, and new technologies are being developed for genetic testing. This Practice Bulletin focuses on the primary genetic mutations associated with hereditary breast and ovarian cancer syndrome, BRCA1 and BRCA2, but also will briefly discuss some of the other genes that have been implicated.

  1. Organization and Running of the First Comprehensive Hereditary Cancer Clinic in India

    OpenAIRE

    Rajkumar, T; Soumittra, N; Vidubala, E; Sridevi, V; Mahajan, V; Ramanan, SG; Vijaya, S

    2005-01-01

    Abstract Hereditary cancers are thought to account for around 5% of cancers, particularly breast/ovarian and colorectal cancers. In India there is a paucity of data on hereditary cancers and the mutations in some of the common genes linked to hereditary cancers, such as BRCA1, BRCA2, hMSH2 and hMLH1. The country's first comprehensive hereditary cancer clinic was established in February 2002. The article describes the organization and running of the Clinic. It also discusses some of the social...

  2. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability

    National Research Council Canada - National Science Library

    Umar, Asad; Boland, C Richard; Terdiman, Jonathan P; Syngal, Sapna; de la Chapelle, Albert; Rüschoff, Josef; Fishel, Richard; Lindor, Noralane M; Burgart, Lawrence J; Hamelin, Richard; Hamilton, Stanley R; Hiatt, Robert A; Jass, Jeremy; Lindblom, Annika; Lynch, Henry T; Peltomaki, Païvi; Ramsey, Scott D; Rodriguez-Bigas, Miguel A; Vasen, Hans F A; Hawk, Ernest T; Barrett, J Carl; Freedman, Andrew N; Srivastava, Sudhir

    2004-01-01

    Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, neoplastic lesions, and microsatellite instability (MSI...

  3. 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.

  4. SUBJECT INDEX

    Indian Academy of Sciences (India)

    Subject Index. Variation of surface electric field during geomagnetic disturbed period at Maitri, Antarctica. 1721. Geomorphology. A simple depression-filling method for raster and irregular elevation datasets. 1653. Decision Support System integrated with Geographic. Information System to target restoration actions in water-.

  5. Ace Inhibitors and Angioedema

    NARCIS (Netherlands)

    Vleeming W; van Amsterdam JGC; de Wildt DJ; Stricker B; TOX

    1995-01-01

    Dit rapport beschrijft de risico's die verbonden zijn aan het gebruik van angiotensine converting enzym (ACE) remmers. Hierbij staat de bijwerking angio-oedeem centraal. De benodigde literatuur is verzameld aan de hand van een zoekaktie middels MEDLINE. ACE-remmers zijn in gebruik ter

  6. 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.

  7. Differentiating Leber Hereditary Optic Neuropathy from Normal-Tension Glaucoma.

    Science.gov (United States)

    Souto, Fernanda Maria Silveira; de Vasconcellos, José Paulo Cabral; de Melo, Mônica Barbosa; Sartorato, Edi Lúcia; Moura, Frederico Castelo

    2017-04-01

    Glaucoma is a neurodegenerative disorder characterized by thinning of neuroretinal rim, enlarged cup-to-disc ratio (CDR) and visual field damage. Although raised intraocular pressure is main risk factor for development of glaucoma, it can occur with consistently normal measurements in the intraocular pressure as normal tension glaucoma (NTG). Enlargement of CDR is a classical sign of glaucoma, but it can also result from non-glaucomatous optic neuropathies such as Leber hereditary optic neuropathy (LHON). We describe a case of LHON with increased CDR, discuss its differential diagnosis with NTG and highlight the reasons for misdiagnoses between these two entities.

  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. Hereditary spastic paraplegias: membrane traffic and the motor pathway.

    Science.gov (United States)

    Blackstone, Craig; O'Kane, Cahir J; Reid, Evan

    2011-01-01

    Voluntary movement is a fundamental way in which animals respond to, and interact with, their environment. In mammals, the main CNS pathway controlling voluntary movement is the corticospinal tract, which encompasses connections between the cerebral motor cortex and the spinal cord. Hereditary spastic paraplegias (HSPs) are a group of genetic disorders that lead to a length-dependent, distal axonopathy of fibres of the corticospinal tract, causing lower limb spasticity and weakness. Recent work aimed at elucidating the molecular cell biology underlying the HSPs has revealed the importance of basic cellular processes — especially membrane trafficking and organelle morphogenesis and distribution— in axonal maintenance and degeneration.

  10. Synthetic dural graft septoplasty in epistaxis from hereditary hemorrhagic telangiectasia.

    Science.gov (United States)

    Burckhardt B, Wilfred; Guerra, Claudia Patricia

    2013-07-01

    It is an autosomal dominant vascular disorder, which has a variety of clinical manifestations, with epistaxis being one of the most common. Many treatment options exist for epistaxis, but with no consensus on which is the method of choice. We describe the case of a patient with hereditary hemorrhagic telangiectasia (HHT) secondary epistaxis with septoplasty managed with synthetic hard graft, which improved intensity and frequency of bleeding episodes. This technique is a variant of the septodermoplasty described by several authors, but the use of synthetic dura can help in obtaining better results and avoid taking skin grafts from other sites different from the surgical site.

  11. 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.

  12. 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 $A$

  13. Hereditary leiomyomatosis and renal cell cancer syndrome: a family affair.

    Science.gov (United States)

    Teh, Jiasian; Kinnear, Ned; Douglass-Molloy, Hannah; Hennessey, Derek Barrry

    2017-01-25

    A 49-year-old woman with cutaneous and uterine leiomyomas, flank pain and a family history of hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome sought genetic testing. She was found to harbour a fumarate hydratase (FH) genetic mutation and a previously undetected renal tumour. The patient underwent radical nephrectomy, and remains well at follow-up. HLRCC syndrome is a rare autosomal dominant disease, with patients at increased risk for cutaneous leiomyomas, early-onset uterine leiomyomas and aggressive renal carcinoma. Although the syndrome may manifest life-threatening complications, outcomes may be improved by preventative family screening and surveillance, compelling early diagnosis. 2017 BMJ Publishing Group Ltd.

  14. 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.

  15. 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.

  16. 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.

  17. Hereditary breast and ovarian cancer: new genes in confined pathways.

    Science.gov (United States)

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

    2016-09-01

    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.

  18. Predisposing genes in hereditary breast and ovarian cancer

    OpenAIRE

    Huusko, P. (Pia)

    1999-01-01

    Abstract In the present study, mutations in BRCA1 and BRCA2, the two major genes predisposing individuals to hereditary breast and ovarian cancer, were screened in Finnish and Turkish cancer families. Germline BRCA1 mutations were found in 7% (6/88) and BRCA2 mutations in 6% (5/88) of the Finnish families studied in Oulu. Two distinct BRCA1 (3745delT, 4216nt-2A→G) and three BRCA2 (999delTCAAA, 6503delTT, 9346nt-2A→G) mutations were identified, all of which are recurrently found in Finland....

  19. A case of hereditary sensory autonomic neuropathy type IV

    Directory of Open Access Journals (Sweden)

    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. Hereditary kidney diseases: highlighting the importance of classical Mendelian phenotypes.

    Science.gov (United States)

    Benoit, Geneviève; Machuca, Eduardo; Heidet, Laurence; Antignac, Corinne

    2010-12-01

    A Mendelian inheritance underlies a nonnegligible proportion of hereditary kidney diseases, suggesting that the encoded proteins are essential for maintenance of the renal function. The identification of genes involved in congenital anomalies of the kidney and in familial forms of nephrotic syndrome significantly increased our understanding of the renal development and kidney filtration barrier physiology. This review will focus on the classical phenotype and clinical heterogeneity observed in the monogenic forms of these disorders. In addition, the role of susceptibility genes in kidney diseases with a complex inheritance will also be discussed. © 2010 New York Academy of Sciences.

  1. [Xanthine oxidase deficiency (hereditary xanthinuria), molybdenum cofactor deficiency].

    Science.gov (United States)

    Sumi, S; Wada, Y

    1996-12-01

    Hereditary xanthinuria is a rare autosomal recessive disorder, with xanthine oxidase deficiency. Patients often display renal symptoms because they excrete a large amounts of xanthine in urine. An high-fluid-intake, alow-purine-food, and alkalinization of urine are effective in the patients. Molybdenum cofactor is essential for xanthine oxidase, sulfite oxidase and aldehyde oxidase. Patients with molybdenum cofactor deficiency display severe neurological symptoms, such as severe convulsions. The patients increase urinary excretions of xanthine and sulfite. Treatments are ineffective for neurological symptoms.

  2. Descriptive Epidemiology, Molecular Biology and Genetics of Hereditary Prostate Cancer in Denmark

    DEFF Research Database (Denmark)

    Bentzon, Diem Nguyen

    2012-01-01

    A search for markers that can differentiate indolent prostate cancers from more aggressive forms. Assessment of clinical differences between hereditary and sporadicc prostate cancer.......A search for markers that can differentiate indolent prostate cancers from more aggressive forms. Assessment of clinical differences between hereditary and sporadicc prostate cancer....

  3. Cuban epidemic optic neuropathy and its relationship to toxic and hereditary optic neuropathy.

    Science.gov (United States)

    Santiesteban-Freixas, Rosaralis; Mendoza-Santiesteban, Carlos E; Columbie-Garbey, Yannara; Quevedo, Alina Gonzalez; Garcia, Alberto Gonzalez; Rodríguez, Ramón Cabal

    2010-07-01

    The similarities and differences between toxic/nutritional and hereditary optic neuropathy and the pathophysiologic mechanisms that they have in common are described. This is based on data from the epidemic suffered in Cuba in 1992, which affected the optic nerves of many individuals and the experience of the authors in dealing with various toxic optic neuropathies, as well as Leber's hereditary optic neuropathy.

  4. Uptake of prenatal diagnostic testing for retinoblastoma compared to other hereditary cancer syndromes in the Netherlands

    NARCIS (Netherlands)

    Dommering, Charlotte J.; Henneman, Lidewij; van der Hout, Annemarie H.; Jonker, Marianne A.; Tops, Carli M. J.; van den Ouweland, Ans M. W.; van der Luijt, Rob B.; Mensenkamp, Arjen R.; Hogervorst, Frans B. L.; Redeker, Egbert J. W.; de Die-Smulders, Christine E. M.; Moll, Annette C.; Meijers-Heijboer, Hanne

    Since the 1980s the genetic cause of many hereditary tumor syndromes has been elucidated. As a consequence, carriers of a deleterious mutation in these genes may opt for prenatal diagnoses (PND). We studied the uptake of prenatal diagnosis for five hereditary cancer syndromes in the Netherlands.

  5. Uptake of prenatal diagnostic testing for retinoblastoma compared to other hereditary cancer syndromes in the Netherlands

    NARCIS (Netherlands)

    C.J. Dommering (Charlotte); L. Henneman (Lidewij); A.H. van der Hout (Annemarie); M.A. Jonker (Marianne); C. Tops (Carli); A.M.W. van den Ouweland (Ans); R.B. van der Luijt (Rob); Mensenkamp, A.R. (Arjen R.); F.B.L. Hogervorst (Frans); E.J.W. Redeker (Egbert); C. de Die-Smulders (Christine); A.C. Moll (Annette); E.J. Meijers-Heijboer (Hanne)

    2017-01-01

    textabstractSince the 1980s the genetic cause of many hereditary tumor syndromes has been elucidated. As a consequence, carriers of a deleterious mutation in these genes may opt for prenatal diagnoses (PND). We studied the uptake of prenatal diagnosis for five hereditary cancer syndromes in the

  6. Uptake of prenatal diagnostic testing for retinoblastoma compared to other hereditary cancer syndromes in the Netherlands

    NARCIS (Netherlands)

    Dommering, C.J.; Henneman, L.; Hout, A.H. van der; Jonker, M.A.; Tops, C.M.; Ouweland, A.M. van den; Luijt, R.B. van der; Mensenkamp, A.R.; Hogervorst, F.B.; Redeker, E.J.; Die-Smulders, C.E.M. de; Moll, A.C.; Meijers-Heijboer, H.

    2017-01-01

    Since the 1980s the genetic cause of many hereditary tumor syndromes has been elucidated. As a consequence, carriers of a deleterious mutation in these genes may opt for prenatal diagnoses (PND). We studied the uptake of prenatal diagnosis for five hereditary cancer syndromes in the Netherlands.

  7. Canine hereditary nephropathies : Molecular genetic studies in Norwegian Elkhounds and English Cocker Spaniels

    NARCIS (Netherlands)

    Wiersma, A.C.

    2007-01-01

    Hereditary nephropathies have been described in a variety of dog breeds. The causative mutation has been identified in a minority of canine renal diseases, and these provide useful animal models to study in order to gain knowledge on human nephropathies. In this thesis, canine hereditary

  8. 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

  9. Methylation profiles of the BRCA1 promoter in hereditary and sporadic breast cancer among Han Chinese.

    Science.gov (United States)

    Pang, Da; Zhao, Yashuang; Xue, Weinan; Shan, Ming; Chen, Yanbo; Zhang, Youxue; Zhang, Guoqiang; Liu, Feng; Li, Dalin; Yang, Yanmei

    2012-09-01

    The development of breast cancer is a multistep process associated with complex changes in host gene expression patterns including inactivation of tumor suppressor genes and activation of oncogenes. Critically, hereditary predisposition plays a significant role in cancer susceptibility. However, mutation of the BRCA1 gene is found only in the minority of hereditary breast cancer, which indicates that there might be alternative, novel mechanisms contributing to inactivation of the BRCA1 gene. Studies have shown that aberrant methylation of genomic DNA plays an important role in carcinogenesis. The aim of this study was to investigate whether DNA methylation may be an alternative mechanism for the inactivation of BRCA1 as an epigenetic modification of the genome and whether hereditary breast cancer has a different BRCA1 methylation phenotype pattern than sporadic breast cancer. The pattern of CpG island methylation within the promoter region of BRCA1 was assessed by bisulfite sequencing DNA from peripheral blood cells of 72 patients with hereditary predisposition but without BRCA1 mutations and 30 sporadic breast cancer controls. The overall methylation level in patients with hereditary predisposition was significantly lower than that in the sporadic control group. However, patients with hereditary predisposition showed a significantly higher methylation susceptibility for the sites -518 when compared to controls. These results suggest that there might be different BRCA1 promoter methylation levels and patterns in sporadic and hereditary breast cancer in peripheral blood DNA. These findings may facilitate the early diagnosis of hereditary breast cancer.

  10. 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%

  11. Hereditary xanthinuria: report on three patients and short review of the literature.

    Science.gov (United States)

    Frayha, R A; Salti, I S; Arnaout, A; Khatchadurian, A; Uthman, S M

    1977-01-01

    Three patients with hereditary xanthinuria are presented and the pertinent literature is reviewed. In two siblings the disease has been asymptomatic; in the third urolithiasis has developed. Xanthine stone formation is the clinical hallmark of the disease. Hereditary xanthinuria seems to be relatively prevalent in Lebanon.

  12. Treatment for speech disorder in Friedreich ataxia and other hereditary ataxia syndromes.

    Science.gov (United States)

    Vogel, Adam P; Folker, Joanne; Poole, Matthew L

    2014-10-28

    Hereditary ataxia syndromes can result in significant speech impairment, a symptom thought to be responsive to treatment. The type of speech impairment most commonly reported in hereditary ataxias is dysarthria. Dysarthria is a collective term referring to a group of movement disorders affecting the muscular control of speech. Dysarthria affects the ability of individuals to communicate and to participate in society. This in turn reduces quality of life. Given the harmful impact of speech disorder on a person's functioning, treatment of speech impairment in these conditions is important and evidence-based interventions are needed. To assess the effects of interventions for speech disorder in adults and children with Friedreich ataxia and other hereditary ataxias. On 14 October 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, CINAHL Plus, PsycINFO, Education Resources Information Center (ERIC), Linguistics and Language Behavior Abstracts (LLBA), Dissertation Abstracts and trials registries. We checked all references in the identified trials to identify any additional published data. We considered for inclusion randomised controlled trials (RCTs) or quasi-RCTs that compared treatments for hereditary ataxias with no treatment, placebo or another treatment or combination of treatments, where investigators measured speech production. Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias of included studies using the standard methodological procedures expected by The Cochrane Collaboration. The review authors collected information on adverse effects from included studies. We did not conduct a meta-analysis as no two studies utilised the same assessment procedures within the same treatment. Fourteen clinical trials, involving 721 participants, met the criteria for inclusion in the review. Thirteen studies compared a pharmaceutical treatment with placebo (or a

  13. High Mitochondrial DNA Copy Number Is a Protective Factor From Vision Loss in Heteroplasmic Leber's Hereditary Optic Neuropathy (LHON).

    Science.gov (United States)

    Bianco, Angelica; Bisceglia, Luigi; Russo, Luciana; Palese, Luigi L; D'Agruma, Leonardo; Emperador, Sonia; Montoya, Julio; Guerriero, Silvana; Petruzzella, Vittoria

    2017-04-01

    Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease that typically causes bilateral blindness in young men. It is characterized by as yet undisclosed genetic and environmental factors affecting the incomplete penetrance. We identified 27 LHON subjects who possess heteroplasmic primary LHON mutations. Mitochondrial DNA (mtDNA) copy number was evaluated. The presence of centrocecal scotoma, an edematous, hyperemic optic nerve head, and vascular tortuosity, as well as telangiectasia was recognized in affected subjects. We found higher cellular mtDNA content in peripheral blood cells of unaffected heteroplasmic mutation carriers with respect to the affected. The increase of cellular mtDNA content prevents complete loss of vision despite the presence of a heteroplasmic state of LHON primary mutation, suggesting that it is a key factor responsible for penetrance of LHON.

  14. Robotic gait training improves motor skills and quality of life in hereditary spastic paraplegia.

    Science.gov (United States)

    Bertolucci, F; Di Martino, S; Orsucci, D; Ienco, E Caldarazzo; Siciliano, G; Rossi, B; Mancuso, M; Chisari, C

    2015-01-01

    Gait impairment, balance problems and falls have a negative impact on independence in ADL and quality of life of patients affected by Hereditary Spastic Paraplegia (HSP). Since no pharmacological options are available, treatments rely mostly on rehabilitation therapy, although almost no data on this topic exist. Given the demonstrated effectiveness of robotics in improving gait and balance in various neurological diseases, aim of this study is to test the effectiveness of a robotic-aided program of gait training on balance, walking ability and quality of life in adult subjects affected by uncomplicated HSP. Thirteen patients affected by uncomplicated HSP were subjected to a six-week robotic-aided gait training protocol. Participants underwent a battery of 3 walking test, 1 balance test and 2 quality of life questionnaires. At the end of the treatment a significant improvement of balance, walking ability and quality of life was observed in almost all the tests. The improvements were maintained over a two-month follow-up period. Our study indicates that a robotic gait training is long term effective in improving balance and walking ability with a positive impact on quality of life in patients affected by uncomplicated form of HSP. As currently there is no specific treatment to prevent or reverse HSP progression, our contribution would be significant for the development of exercise recommendations in this rare disease.

  15. Male prevalence of acquired color vision defects in asymptomatic carriers of Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Ventura, Dora Fix; Gualtieri, Mirella; Oliveira, André G F; Costa, Marcelo F; Quiros, Peter; Sadun, Federico; de Negri, Anna Maria; Salomão, Solange R; Berezovsky, Adriana; Sherman, Jerome; Sadun, Alfredo A; Carelli, Valerio

    2007-05-01

    Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease resulting in loss of central vision and dyschromatopsia, caused by mitochondrial DNA point mutations. However, only a subset of the mutation carriers becomes affected, with a higher penetrance in males. This study was conducted to investigate chromatic losses in asymptomatic carriers of the LHON mutation. Monocular chromatic discrimination was studied with the Cambridge Colour Test (CCT; Cambridge Research Systems, Ltd., Rochester, UK) along the protan, deutan, and tritan cone isolation axes in 46 LHON carriers (15 men) belonging to the same LHON maternal lineage and 74 age-matched control subjects (39 men). Inclusion criteria were absence of ophthalmic complaints and clear ocular media. A detailed neuro-ophthalmic examination was performed in all the LHON carriers. The differences in threshold between carriers and control subjects were significant for the three cone isolation axes at P women for the protan and deutan axes (ANOVA; P women had instances of diffuse defect whereas all the men displayed a red-green defect. Male LHON asymptomatic carriers had color vision losses with the red-green pattern of dyschromatopsia typical of patients affected with LHON, which includes elevation of tritan thresholds as well. This predominantly parvocellular (red-green) impairment is compatible with the histopathology of LHON, which affects mostly the papillomacular bundle. In contrast with male losses, female losses were less frequent and severe. These gender differences are relevant to understanding LHON pathophysiology, suggesting that hormonal factors may be of great importance.

  16. Genetics of human isolated hereditary hair loss disorders.

    Science.gov (United States)

    Basit, S; Khan, S; Ahmad, W

    2015-09-01

    Hereditary hair loss in human is a group of clinically and genetically heterogeneous disorders. It is characterized by sparse to complete absence of hair on the scalp and other parts of the body. In few cases tightly curled twisted wooly hair (WH) on the scalp has been reported as well. The hair loss disorders, including both syndromic and non-syndromic (isolated) forms, segregate either in autosomal dominant or autosomal recessive pattern. To date, seven autosomal dominant and equal numbers of autosomal recessive isolated forms of hair loss disorders have been characterized. Genes responsible for causing most of these disorders have been identified. In this review, we have provided an update on clinical and genetic aspects of isolated hereditary hair loss disorders manifesting with hypotrichosis and/or WHs. Because most of the recessive genes have been mapped using consanguineous families of Pakistani origin, therefore emphasis is given to mutations identified in these families. OMIM nomenclature has been followed to indicate different forms of hair loss disorders. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Targeted high throughput sequencing in hereditary ataxia and spastic paraplegia.

    Science.gov (United States)

    Iqbal, Zafar; Rydning, Siri L; Wedding, Iselin M; 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.

  18. New genetic causes for complex hereditary spastic paraplegia.

    Science.gov (United States)

    Souza, Paulo Victor Sgobbi de; Bortholin, Thiago; Dias, Renan Braido; Chieia, Marco Antônio Troccoli; Burlin, Stênio; Naylor, Fernando George Monteiro; Pinto, Wladimir Bocca Vieira de Rezende; Oliveira, Acary Souza Bulle

    2017-08-15

    Hereditary Spastic Paraplegia (HSP) represents a complex and heterogeneous group of rare neurodegenerative disorders that share a common clinical feature of weakness and lower limb spasticity that can occur alone or in combination with a constellation of other neurological or systemic signs and symptoms. Although the core clinical feature of weakness and lower limb spasticity is virtually universal, the genetic heterogeneity is almost uncountable with more than 70 genetic forms described so far. We performed review of medical records from twenty-one patients from seventeen Brazilian families with complex phenotype of HSP. All cases have previously negative mutations in SPG11/KIAA1840 and SPG7 gene and were evaluated by whole-exome sequencing. An extensive description of systemic and neurological signs has been described. Whole-exome sequencing was unremarkable in eight patients and established a definite genetic diagnosis in thirteen patients of twelve non-related families. Mutations were found in genes previously implicated in other neurodegenerative disorders such as Amyotrophic Lateral Sclerosis, Hereditary Neuropathy, Spastic Ataxias, Neurodegeneration with Brain Iron Accumulation, Glycogen Metabolism, Congenital Lipodystrophy and aminoacyl-tRNA synthetases disorders. We report thirteen new genetically-proven cases of complex HSP, expanding the clinical spectrum of presentations of HSP, providing new pathophysiological mechanisms and disclosing new potential therapeutic targets. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. 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.

  20. Lateral medullary syndrome in a boy with hereditary dysfibrinogenemia.

    Science.gov (United States)

    Kibe, Tetsuya; Ikeya, Manae; Yokochi, Kenji; Okumura, Nobuo

    2012-11-01

    A 9-year-old boy presented with sudden onset of nausea, vomiting and unsteady gait after a bread-eating game, which possibly caused neck hyperextension. Neurological examination revealed hemisensory loss of pain and temperature sensation in the right trunk and limbs along with left Horner's syndrome, suggesting lateral medullary syndrome (LMS). Magnetic resonance (MR) imaging of the brain revealed infarction at the left lateral medulla. MR angiography showed no sign of arterial dissection and no occlusion or stenosis of the intracranial, basilar or vertebral arteries or their branches. No evidence of cardioemboli or systemic inflammation was apparent. Repeated blood examination revealed low activity of fibrinogen. Genetic testing confirmed the presence of hereditary dysfibrinogenemia with a mutation in the FGB gene (BβGly15Cys). This fibrinogen variant has previously been found in Japanese patients with atherosclerosis obliterans or no symptoms. Under conservative treatment without anticoagulation and aspirin, the patient made a good recovery within a few months. We presume that microthrombosis may have been deposited within the vertebral system as a result of extension and rotation of the neck during sports activity, with a contribution from hereditary dysfibrinogenemia. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.