Efforts by the CIEMAT to diagnose and treat Butterfly children. the CIEMAT in the CIBER of Rare Diseases; Esfuerzos en el CIEMAT por diagnosticas y tratar a los ninos pariposa. El CIEMAT en el CIBER de enfermedades Raraas
Rio Nechaevsky, M. del
The CIEMAT is one of the institutions associated with the Center for Online Biomedical Research of Rare Diseases (CIBERER). The CIBER of Rare diseases is one of the new public consortiums established at the initiative of the Carlos III Institute of Health. It is formed by 60 research groups linked to 30 different institutions. These research groups are the basic operating units and are grouped together in seven scientific areas. With this online structure, the CIBERER is a pioneering initiative to facilitate synergy's between cutting-edge groups and institutions in different areas and disciplines in the field of rare diseases, as well as to ensure that scientific findings are transferred from the laboratory to the clinic, based on the concept of Translational Research. (Author) 13 refs.
Waldman, H. Barry; Perlman, Steven P.; Munter, Beverly L.; Chaudhry, Ramiz A.
A rare disease or condition is defined by federal legislation such that it: (1) affects less than 200,000 persons in the U.S.; or (2) affects more than 200,000 persons in the U.S. but for which there is no reasonable expectation that the cost of developing and making available in the U.S. a drug for such disease or condition will be recovered from…
Umlauf, Mary; Monaco, Jana; FitzZaland, Mary; FitzZaland, Richard; Novitsky, Scott
According to the National Organization for Rare Disorders (NORD), a rare or "orphan" disease affects fewer than 200,000 people in the United States. There are more than 6,000 rare disorders that, taken together, affect approximately 25 million Americans. "Exceptional Parent" ("EP") recognizes that when a disorder affects a child or adult, it…
Full Text Available Rare diseases are diseases with a particularly low prevalence. The specificities of rare diseases - limited number of patients and scarcity of relevant knowledge and expertise - single them out as a distinctive domain of very high added value. The international reference for classification of diseases and conditions is the International Classification of Diseases (ICD, coordinated by the World Health Organization (WHO. Patient registries and databases constitute key instruments for the development of clinical research in the field of rare diseases. Rare disease registries include not only diseases that are inherently rare, but also common diseases that are rare in specific populations, especially those defined by demographics. Disease registries create the possibility of assessing the long-term safety and benefit of different treatments, perhaps leading to treatment algorithms that allow more choices for patients and clinicians.
disease diagnostic hypotheses in the domain of medical IR. In this work, we build upon an existing vertical medical search engine, Zebra, that is focused on rare disease diagnosis. In previous work, Zebra has been evaluated using real-life medical cases of rare and difficult diseases, and has been found...... to be a useful and competitive tool for clinicians. In this work, we extend Zebra’s functionalities to optimise the task of medical diagnosis through search as follows: we add the option of grouping retrieved documents into clusters based on disease name occurrence, and we offer a ‘disease-ranking’ option...
Safavi Naiyni SA
Full Text Available A 16 year old woman with Tangier disease in palatine tonsils is reported. She has recurrent sore throat. In physical examination the palatine tonsils are hypertrophied and has very yellowish points. The facial skin is yellowish but the skin of another areas of body is normal. After tonsillectomy the pathologist report Tangier disease in palatine tonsils
Pfliegler, György; Kovács, Erzsébet; Kovács, György; Urbán, Krisztián; Nagy, Valéria; Brúgós, Boglárka
The present paper is focusing on rare diseases manifesting in late childhood or adulthood. A part of these syndromes are not of genetic origin, such as relatively or absolutely rare infections, autoimmune diseases, tumours, or diseases due to rare environmental toxic agents. In addition, even a large proportion of genetic disorders may develop in adulthood or may have adult forms as well, affecting are almost each medical specialization. Examples are storage disorders (e.g. adult form of Tay-Sachs disease, Gaucher-disease), enzyme deficiencies (e.g. ornithin-transcarbamylase deficiency of the urea cycle disorders), rare thrombophilias (e.g. homozygous factor V. Leiden mutation, antithrombin deficiency), or some rare monogenic disorders such as Huntington-chorea and many others. It is now generally accepted that at least half of the 6-8000 "rare diseases" belong either to the scope of adult-care (e.g. internal medicine, neurology), or to "age-neutral" specialities such as ophtalmology, dermatology etc.).
Mariela Yaneva – Deliverska
Full Text Available Rare diseases are characterised by their low prevalence (less than 1/2,000 and their heterogeneity. They affect both children and adults anywhere in the world. From the medical perspective, rare diseases are characterised by the large number and broad diversity of disorders and symptoms that vary not only from disease to disease, but also within the same disease.Main characteristics of rare diseases include:· Rare diseases are often chronic, progressive, degenerative, and often life-threatening· Rare diseases are disabling: the quality of life of patients is often compromised by the lack or loss of autonomy· High level of pain and suffering for the patient and his/ her family · No existing effective cure· There are between 6000 and 8000 rare diseases· 75% of rare diseases affect children· 30% of rare disease patients die before the age of 5· 80% of rare diseases have identified genetic origins. Other rare diseases are the result of infections (bacterial or viral, allergies and environmental causes, or are degenerative and proliferative.Beyond the diversity of the diseases, rare disease patients and their families are confronted with the same wide range of difficulties arising directly from the rarity of these pathologies. The period between the emergence of the first symptoms and the appropriate diagnosis involves unacceptable and highly risky delays, as well as wrong diagnosis leading to inaccurate treatments. Living with a rare disease has implications in all areas of life, whether school, choice of future work, leisure time with friends, or affective life. It may lead to stigmatisation, isolation, exclusion from social community, discrimination for insurance subscription (health insurance, travel insurance, mortgage, and often reduced professional opportunities.Innovative treatments are often unevenly available in the EU because of delays in price determination and/or reimbursement decision, lack of experience of the treating
Rohan S Valsangkar
Full Text Available Granulomatous inflammation of the prostate is a rare type of inflammation of the prostate. It is of various types, with the non-specific type of granulomatous inflammation being the most common. Xanthogranulomatous prostatitis is a rare type of granulomatous prostatitis of which very few cases have been reported. Histologically it is characterized by the presence of pale-looking foamy macrophages. It can be an incidental finding after transurethral resection of the prostate (TURP, although it may mimic prostatic malignancy clinically, biochemically, and rarely histologically. We report a rare case of xanthogranulomatous prostatitis which presented as a prostatic abscess, a presentation never reported in literature so far. The patient was managed with TURP.
Full Text Available According to the Regulation (EC N. 141/2000 of the European Parliament and of the Council, rare diseases are life-threatening or chronically debilitating conditions, affecting no more than 5 in 10 000 persons in the European Community. It is estimated that between 6000 to 8000 distinct rare diseases affect up to 6% of the total EU population. Therefore, these conditions can be considered rare if taken individually but they affect a significant proportion of the European population when considered as a single group. Several initiatives have been undertaken at international, European and national level to tackle public health as well as research issues related to the prevention, diagnosis, treatment and surveillance of these diseases. The development of innovative and effective medical products for their diagnosis and treatment is frequently hampered by several factors, including the limited knowledge of their natural history, the difficulties in setting up clinical studies due to the limited numbers of patients affected by a specific disease, the weak interest of sponsors due to the restricted market opportunities. Therefore, incentives and other facilitations have been adopted in many parts of the world, including in the EU, in order to facilitate the development and commercialization of diagnostic tools and treatments devoted to rare diseases. This paper illustrates mainly the European initiatives and will discuss the problematic and controversial aspects surrounding orphan drugs. Finally, activities and measures adopted in Italy are presented.
Smetsers, Stephanie E; Takkenberg, J J M Hanneke; Bierings, Marc B
A rare disease usually concerns only a handful of patients, but all patients with a rare disease combined represent a significant health burden. Due to limited knowledge and the absence of treatment guidelines, patients with rare diseases usually experience delayed diagnosis and suboptimal treatment. Historically, rare diseases have never been considered a major health problem. However, rare diseases have recently been receiving increased attention. In the Netherlands, a national plan for rare diseases was published in late 2013, with recommendations on how to improve the organisation of healthcare for people with rare diseases. Using the example of the rare disease Fanconi anemia, this paper describes the challenges and opportunities in organising healthcare for rare diseases. Two critical steps in optimising healthcare for rare diseases are developing multidisciplinary healthcare teams and stimulating patient empowerment. Optimal cooperation between patients, patient organisations, multidisciplinary healthcare teams and scientists is of great importance. In this respect, transition to adult healthcare requires special attention.
Félix Hernández Rodríguez
Full Text Available En este artículo se destaca la importancia de la utilización de esfuerzos y deformaciones equivalentes en el análisis del comportamiento mecánico de los sólidos, con un enfoque centrado en la mecánica de suelos. Solamente se tratarán los aspectos básicos, desde una perspectiva general, sin entrar a detallar la utilización de esos esfuerzos y deformaciones en la solución de problemas particulares de ingeniería. Se resalta la conveniencia de trabajar con unos invariantes, íntimamente relacionados con los cambios volumétricos y distorsiónales del sólido, en lugar de hacerlo con los tensores completos de esfuerzos y de deformaciones.
Rohan Bharat Gala
Full Text Available Hirayama's disease is a rare benign neurological disorder also known as monomelic amyotrophy, Sobue disease, Juvenile Muscular Atrophy of Distal Upper Extremity (JMADUE. It mainly affects young males in their second or third decades and is most commonly seen in Asian countries like Japan, Malaysia and India. In majority of the cases the cause of the disease is unknown. An 18 year male came with weakness in his right hand and forearm since 1 year. Examination revealed weakness and wasting of muscles of forearm and hand without lower limb involvement and normal deep tendon reflexes. MRI showed focal short segment hyperintense signal in the ventral and right lateral aspect of the cervical cord at C5-C6 level with the involved segment measuring 4x3mm in size. Based on clinical and radiological features a diagnosis of focal amyotrophy was made. Patient is given a cervical collar to prevent flexion at the neck and physiotherapy in the form of hand and forearm exercises were started. Regular follow up of the patient once every 2 months is being done. Hirayama's disease is a rare, benign, self-limiting neurological disorder. Early diagnosis and management by preventing cervical flexion with the help of a cervical collar has shown to halt the progression of the disease. [Int J Res Med Sci 2015; 3(3.000: 767-770
Erythromelalgia (EM) is a rare condition of unknown etiology that results in intense, burning pain and redness primarily of the feet, and, even more rarely, in the hands. Most cases are idiopathic (primary EM); others occur secondary to medical conditions, such as autoimmune diseases, and neurological or hematological disorders. Symptoms are episodic and can result in severe disability. Triggers, such as exposure to warmth, pressure or exercise, become apparent to those afflicted with this condition; however, triggers may be unavoidable during the course of daily living. There are no diagnostic tests for EM. Diagnosis is based on history, physical examination during symptomatic episode and the exclusion of other probable causes for the syndrome. Early recognition of the signs and symptoms as well as early treatment offer patients the best hope of remissions and improved quality of life.
... page What are some examples of rare diseases? Examples of rare diseases caused by mutations in single genes include cystic fibrosis, which affects ... responsible for some rare, inherited types of cancer. Examples of these are ... which certain mutations increase the risk for hereditary breast and ovarian ...
Senn, A; Filzmaier, K
A rare disease is defined as a disease that affects a maximum of 5 in 10,000 people. As of today there are roughly 7000 different rare diseases known. On account of this one can say that "rare diseases are rare, but people affected by them are common". For Germany this amounts to: 4 million people that are affected by a rare disease. Diagnosis, therapeutic options and prognosis have substantially improved for some of the rare diseases. Besides the general medical advances--especially in the area of genetics--this is also due to networking and sharing information by so-called Centres of Competence on a national and international scale. This results in a better medical care for the corresponding group of patients. Against this backdrop, the number of people applying for life assurance who are suffering from a complex or rare disease has risen steadily in the last years. Due to the scarce availability of data regarding long-term prognosis of many rare diseases, a biomathematical, medical and actuarial expertise on the part of the insurer is necessary in order to adequately assess the risk of mortality and morbidity. Furthermore there is quite a focus on the issue of rare diseases from not only politics but society as well. Therefore evidence based medical assessment by insurers is especially important in this group of applicants--thinking of legal compliance and reputational risk.
Mendlovic, Joseph; Barash, Hila; Yardeni, Hadar; Banet-Levi, Yonit; Yonath, Hagith; Raas-Rothschild, Annick
Rare diseases are chronic, progressive genetic disorders, which affect around 6-8% of the general population, mainly children. Therefore, in Israel approximately 500,000 people are probably affected by a rare disease. In this article, we review some of the issues pertaining to rare diseases, such as the need for accurate diagnosis which is necessary not only for specific care and treatment but also for informed family planning. In addition, we review the impact of the activities of patients' organizations on the awareness of rare diseases and their involvement in the creation of the Orphan Drug Act, which was the leading point on the way to drug development worldwide. During the last few years networks for reaching leading specialists' opinions on the way to proper diagnosis were created. Thereafter, the next generation genetic technologies, such as exome sequencing, have been a revolution in terms of options and hope for patients with rare undiagnosed diseases. Patients with rare diseases and their families are a challenge to the health care system, not only in terms of diagnosis and therapy, but also in terms of special needs. In addition, deciphering molecular pathways of rare diseases might be the key for understanding molecular events involved in common disorders. We emphasize the duty to ensure appropriate capacity and equal access to follow-up and clinical management of patients with rare diseases in Israel.
Ghulam Rehman Mohyuddin
Full Text Available A 70-year-old female presented with a 4-week history of dry cough and wheezing. Chest radiograph showed a 10.5 cm mass-like density in the anterior mediastinum which had not been previously visualized. Computed tomography scan (CT of the chest showed a right hilar mass encasing and narrowing right upper lobe bronchus and right mainstem bronchus and secondary atelectatic changes. Biopsy was consistent with a diagnosis of lymphomatoid granulomatosis Grade 3. She responded well clinically and radiologically to therapy. Lymphomatoid granulomatosis is a rare EBV-associated disorder which is considered a lymphoproliferative disease. The most common radiographic feature is multiple lung nodules. An isolated hilar mass is an exceptionally rare presentation of this rare disease.
Full Text Available Rare disease patients too often face common problems, including the lack of access to correct diagnosis, lack of quality information on the disease, lack of scientific knowledge of the disease, inequities and difficulties in access to treatment and care. These things could be changed by implementing a comprehensive approach to rare diseases, increasing international cooperation in scientific research, by gaining and sharing scientific knowledge about and by developing tools for extracting and sharing knowledge. A significant aspect to analyze is the organization of knowledge in the biomedical field for the proper management and recovery of health information. For these purposes, the sources needed have been acquired from the Office of Rare Diseases Research, the National Organization of Rare Disorders and Orphanet, organizations that provide information to patients and physicians and facilitate the exchange of information among different actors involved in this field. The present paper shows the representation of rare diseases terms in biomedical terminologies such as MeSH, ICD-10, SNOMED CT and OMIM, leveraging the fact that these terminologies are integrated in the UMLS. At the first level, it was analyzed the overlap among sources and at a second level, the presence of rare diseases terms in target sources included in UMLS, working at the term and concept level. We found that MeSH has the best representation of rare diseases terms.
Full Text Available Actinomycosis is an indolent, slowly progressive infection caused by Actinomyces species. Of human actinomycosis, the spinal form is rare and actinomycosis-related spinal neurological deficit is uncommon. We report two cases with cervical and dorsal actinomycosis and one of them with spinal neurological deficit.
Kawashima Kodama, Tomoko
The progress has been made in research on rare and intractable diseases, for which new drug development has long been limited due to rarity, by establishing a global network in recent years. In Japan, the countermeasure of rare and intractable diseases has been implemented under national policy outline as an integrated strategy since 1972, including surveys and research, construction of medical facilities, reducing burden of medical expenses for patients, and enhancement of welfare and improving QOL of patients. Along with legislation or regulation of orphan drugs development, treatment and care for rare diseases have been emphasized in each national healthcare system globally. In the US, the Office of Rare Diseases was established under NIH in 1989 and European countries also started collaboration for rare disease projects with their own national plans in 1999. As a platform of rare diseases patients, healthcare professionals, researchers, pharmaceutical industry, and policy makers, Orphanet has a well-designed website which networks them. In Japan, there are urgent needs for global standard patient registration system and strengthening global collaboration for developing treatment and care for the patients of rare and intractable diseases, which needs more cooperative relations with patient organizations and pharmaceutical industry within country.
Full Text Available Rare diseases are a heterogenic group of disorders with a little in common except of their rarity affecting by less than 5 : 10.000 people. In the world is registered about 6000-8000 rare diseases with 6-8% suffering population only in the European Union. In spite of rarity, they represent an important medical and social problem due to their incidence. For many rare diseases have no treatment, but if it exists and if started on time as being available to patients, there is a good prognosis for them to be able for normal life. The problems of patients affected by rare diseases are related to the lack of diagnosis and timely undergoing as well as their treatment or prevention. Orphan drugs are products intended for treatment, diagnosis or prevention of rare diseases, but for their development and marketing the industry has not been interested in yet because of their marketing reasons. Patients suffering from a rare disease although belonging to the vulnerable group for their specific health needs, is becoming invisible in the health care system due to their additional needs un properly recognized. Ethical problems faced by patients, but also health care professionals are related to the allocation of medical diagnostics, unequal approach to health care, inappropriately specialized social services as well as therapy and rare orphan drugs unavailability. Ethical questions related to clinical trails on orphan drugs, population screening and epidemiology testing on rare diseases will also be discussed in this paper. [Projekat Ministarstva nauke Republike Srbije, br. 41004: Rare diseases: Molecular pathophysiology, the diagnostic and therapeutical modalities, social, ethical and legal aspects
Federal Laboratory Consortium — There are more than 6,500 identified rare and neglected diseases, yet only about 250 treatments are available for these conditions. The limited numbers of patients...
Shukla, Ravindra; Basu, Asish Kumar; Mandal, Biplab; Mukhopadhyay, Pradip; Maity, Animesh; Sinha, Anirban
Idiopathic Hypogonadotropic hypogonadism (IHH) phenotype is variable &various genes have been decribed in association with IHH. We describe association of IHH with mosaic trisomy 13. A 20 year old male presented with lack of development of secondary sexual characters, normal height, micropenis, small testes, gynaecomastia, absence of axillary and pubic hairs, hyposmia, synkinesis, bilateral horizontal nystagmus and high arched palate. Investigations showed low gonadotropin, low total testosterone, LH after stimulation with 100 mcg tryptorelin sc was 11.42 mU/mL at 40 min. MRI of hypothalamo-pituitary region showed normal olfactory bulb and tract but shallow olfactory sulcus. Karyotype showed homologous Robertsonian translocation of chromosome 13. This case fits classical IHH except for LH rise on stimulation. Features of Patau syndrome which is associated with trisomy 13 are absent in our case. Mosaic trisomy 13, which can otherwise be rare incidental finding, has not been described in association with IHH. Causal association of novel mutation on chromosome 13 leading to aforementioned phenotype cannot be rule out. PMID:24251138
Full Text Available Idiopathic Hypogonadotropic hypogonadism (IHH phenotype is variable & various genes have been decribed in association with IHH.We describe association of IHH with mosaic trisomy 13. A 20 year old male presented with lack of development of secondary sexual characters, normal height, micropenis, small testes, gynaecomastia, absence of axillary and pubic hairs, hyposmia,synkinesis, bilateral horizontal nystagmus and high arched palate. Investigations showed low gonadotropin,low total testosterone, LH after stimulation with 100 mcg tryptorelin sc was 11.42 mU/mL at 40 min. MRI of hypothalamo-pituitary region showed normal olfactory bulb and tract but shallow olfactory sulcus . Karyotype showed homologous Robertsonian translocation of chromosome 13. This case fits classical IHH except for LH rise on stimulation.Features of Patau syndrome which is associated with trisomy 13 are absent in our case. Mosaic trisomy 13, which can otherwise be rare incidental finding , has not been described in association with IHH.Causal association of novel mutation on chromosome 13 leading to aforementioned phenotype cannot be rule out.
Lacka, Katarzyna; Maciejewski, Adam
Rare diseases are usually defined as entities affecting less than 1 person per 2,000. About 7,000 different rare entities are distinguished and, among them, rare diseases of the thyroid gland. Although not frequent, they can be found in the everyday practice of endocrinologists and should be considered in differential diagnosis. Rare non-neoplastic thyroid diseases will be discussed. Congenital hypothyroidism's frequency is relatively high and its early treatment is of vital importance for neonatal psychomotor development; CH is caused primarily by thyroid dysgenesis (85%) or dyshormonogenesis (10-15%), although secondary defects - hypothalamic and pituitary - can also be found; up to 40% of cases diagnosed on neonatal screening are transient. Inherited abnormalities of thyroid hormone binding proteins (TBG, TBP and albumin) include alterations in their concentration or affinity for iodothyronines, this leads to laboratory test abnormalities, although usually with normal free hormones and clinical euthyroidism. Thyroid hormone resistance is most commonly found in THRB gene mutations and more rarely in THRA mutations; in some cases both genes are unchanged (non-TR RTH). Recently the term 'reduced sensitivity to thyroid hormones' was introduced, which encompass not only iodothyronine receptor defects but also their defective transmembrane transport or metabolism. Rare causes of hyperthyroidism are: activating mutations in TSHR or GNAS genes, pituitary adenomas, differentiated thyroid cancer or gestational trophoblastic disease; congenital hyperthyroidism cases are also seen, although less frequently than CH. Like other organs and tissues, the thyroid can be affected by different inflammatory and infectious processes, including tuberculosis and sarcoidosis. In most of the rare thyroid diseases genetic factors play a key role, many of them can be classified as monogenic disorders. Although there are still some limitations, progress has been made in our understanding of
Litterman, Nadia K.; Rhee, Michele; Swinney, David C.; Ekins, Sean
Rare disease research has reached a tipping point, with the confluence of scientific and technologic developments that if appropriately harnessed, could lead to key breakthroughs and treatments for this set of devastating disorders. Industry-wide trends have revealed that the traditional drug discovery research and development (R&D) model is no longer viable, and drug companies are evolving their approach. Rather than only pursue blockbuster therapeutics for heterogeneous, common diseases, drug companies have increasingly begun to shift their focus to rare diseases. In academia, advances in genetics analyses and disease mechanisms have allowed scientific understanding to mature, but the lack of funding and translational capability severely limits the rare disease research that leads to clinical trials. Simultaneously, there is a movement towards increased research collaboration, more data sharing, and heightened engagement and active involvement by patients, advocates, and foundations. The growth in networks and social networking tools presents an opportunity to help reach other patients but also find researchers and build collaborations. The growth of collaborative software that can enable researchers to share their data could also enable rare disease patients and foundations to manage their portfolio of funded projects for developing new therapeutics and suggest drug repurposing opportunities. Still there are many thousands of diseases without treatments and with only fragmented research efforts. We will describe some recent progress in several rare diseases used as examples and propose how collaborations could be facilitated. We propose that the development of a center of excellence that integrates and shares informatics resources for rare diseases sponsored by all of the stakeholders would help foster these initiatives. PMID:25685324
Litterman, Nadia K; Rhee, Michele; Swinney, David C; Ekins, Sean
Rare disease research has reached a tipping point, with the confluence of scientific and technologic developments that if appropriately harnessed, could lead to key breakthroughs and treatments for this set of devastating disorders. Industry-wide trends have revealed that the traditional drug discovery research and development (R&D) model is no longer viable, and drug companies are evolving their approach. Rather than only pursue blockbuster therapeutics for heterogeneous, common diseases, drug companies have increasingly begun to shift their focus to rare diseases. In academia, advances in genetics analyses and disease mechanisms have allowed scientific understanding to mature, but the lack of funding and translational capability severely limits the rare disease research that leads to clinical trials. Simultaneously, there is a movement towards increased research collaboration, more data sharing, and heightened engagement and active involvement by patients, advocates, and foundations. The growth in networks and social networking tools presents an opportunity to help reach other patients but also find researchers and build collaborations. The growth of collaborative software that can enable researchers to share their data could also enable rare disease patients and foundations to manage their portfolio of funded projects for developing new therapeutics and suggest drug repurposing opportunities. Still there are many thousands of diseases without treatments and with only fragmented research efforts. We will describe some recent progress in several rare diseases used as examples and propose how collaborations could be facilitated. We propose that the development of a center of excellence that integrates and shares informatics resources for rare diseases sponsored by all of the stakeholders would help foster these initiatives.
Reis, Edimara S; Mastellos, Dimitrios C; Yancopoulou, Despina; Risitano, Antonio M; Ricklin, Daniel; Lambris, John D
Around 350 million people worldwide suffer from rare diseases. These may have a genetic, infectious, or autoimmune basis, and several include an inflammatory component. Launching of effective treatments can be very challenging when there is a low disease prevalence and limited scientific insights into the disease mechanisms. As a key trigger of inflammatory processes, complement has been associated with a variety of diseases and has become an attractive therapeutic target for conditions involving inflammation. In view of the clinical experience acquired with drugs licensed for the treatment of rare diseases such as hereditary angioedema and paroxysmal nocturnal hemoglobinuria, growing evidence supports the safety and efficacy of complement therapeutics in restoring immune balance and preventing aggravation of clinical outcomes. This review provides an overview of the candidates currently in the pharmaceutical pipeline with potential to treat orphan diseases and discusses the molecular mechanisms triggered by complement involved with the disease pathogenesis.
Walat, Anna; Skoczylas, Michal Marian; Welnicka, Agnieszka; Kulig, Malgorzata; Rodak, Przemyslaw; Walczak, Zuzanna; Jablońska, Agata
The aim of the study was to assess knowledge about rare diseases among citizens of Szczecin (Poland). The study was performed by questioning 242 adult customers of Turzyn Shopping Centre in Szczecin (149 females and 93 males). The survey was conducted in the shopping mall on 23 February 2013 (control group) and during the celebration of Rare Disease Day and the 12th Polish Nationwide Cystic Fibrosis Week ("Dolina Mukolinków") on 2 March 2013 (research group). The research tool was a questionnaire devised by the authors and filled out by the writing authors interviewer's answers. In the study group more people knew about the existence of Rare Disease Day than in the control group (86.02% vs 57.72%, chi-square test χ2 > χ2(1); 0.001, p χ2(1); 0.001, p < 0.001). The respondents from the research group knew more about Rare Disease Day and defined the idea of it as closed in a significantly higher degree than the control group. There was no significant difference in the detailed knowledge about rare diseases in either group. This might indicate the need to educate society and patients, along with their families.
A disease is considered rare if it affects no more than 5 in 10,000 people. More than six thousand rare diseases have been detected so far and they affect 6-8% of the population which equals 2.3-3 million people in Poland. Some of the rare diseases are already diagnosed in utero, e.g. skeletal dysplasias on ultrasonography or central nervous system diseases on magnetic resonance imaging (MRI). Many cases are finally diagnosed after radiologist's suggestion in a radiological report. Although diagnostic imaging cannot be considered as a basis for diagnosis of most of rare diseases, these studies represent an important element in the diagnostic chain. The complicated and long process of diagnosis may be significantly shortened by suggestions of the radiologist, based on the observation of these elements of radiological appearance of the lesions that are characteristic for a particular group of diseases, or even for a particular disease entity. However, the absolute condition for success is the close clinical-radiological cooperation, with clinicians providing the radiologists with their knowledge of patient's history, clinical manifestations, and the results of other investigations.
Landais, Paul; Messiaen, Claude; Rath, Ana; Le Mignot, Loïc; Dufour, Eric; Ben Said, Mohamed; Jais, Jean-Philippe; Toubiana, Laurent; Baujat, Geneviève; Bourdon-Lanoy, Eva; Gérard-Blanluet, Marion; Bodemer, Christine; Salomon, Rémi; Aymé, Ségolène; Le Merrer, Martine; Verloes, Alain
Rare diseases cover a group of conditions characterized by a low prevalence, affecting less than 1 in 2,000 people; 5000 to 7000 rare diseases have been currently identified in Europe. Most diseases do not have any curative treatment. They represent thus an important public health concern. CEMARA is based on a n-tier architecture. Its main objective is to collect continuous and complete records of patients with rare diseases, and their follow-up through a web-based Information System, and to analyse the epidemiological patterns. In France, 41 out of 131 labelled Reference Centres (RC) are sharing CEMARA. Presently 56,593 cases have been registered by more than 850 health care professionals belonging to 171 clinical sites. The national demand of care was explored in relation with the offer of care in order to reach an improved match. Within 2 years, CEMARA stimulated sharing a common platform, a common ontology with Orphanet and initiating new cohorts of rare diseases for improving patient care and research.
... of Health and Food and Drug Administration definitions when making coverage decisions for treatments... Office of the Secretary 32 CFR Part 199 RIN 0720-AB26 TRICARE; Rare Diseases Definition AGENCY: Office of the Secretary, DoD. ACTION: Final rule. SUMMARY: This final rule revises the definition of...
Sriram Bhat M
Full Text Available Free peritoneal perforation is a rare complication of Crohn's disease with a report of only 100 cases in the literature. It needs an emergency exploration and an unaware general surgeon is confounded in intraoperative decision-making. We present our experience when this rarity struck us in a district hospital and briefly review the guidelines of optimal management of this complication of Crohn's disease.
Müller, T; Jerrentrup, A; Schäfer, J R
To establish a comprehensive diagnosis is by far the most challenging task in a physician's daily routine. Especially rare diseases place high demands on differential diagnosis, caused by the high number of around 8000 diseases and their clinical variability. No clinician can be aware of all the different entities and memorizing them all is impossible and inefficient. Specific diagnostic decision-supported systems provide better results than standard search engines in this context. The systems FindZebra, Phenomizer, Orphanet, and Isabel are presented here concisely with their advantages and limitations. An outlook is given to social media usage and big data technologies. Due to the high number of initial misdiagnoses and long periods of time until a confirmatory diagnosis is reached, these tools might be promising in practice to improve the diagnosis of rare diseases.
Schumacher, Kurt R; Stringer, Kathleen A; Donohue, Janet E; Yu, Sunkyung; Shaver, Ashley; Caruthers, Regine L; Zikmund-Fisher, Brian J; Fifer, Carlen; Goldberg, Caren; Russell, Mark W
For pediatric rare diseases, the number of patients available to support traditional research methods is often inadequate. However, patients who have similar diseases cluster "virtually" online via social media. This study aimed to (1) determine whether patients who have the rare diseases Fontan-associated protein losing enteropathy (PLE) and plastic bronchitis (PB) would participate in online research, and (2) explore response patterns to examine social media's role in participation compared with other referral modalities. A novel, internet-based survey querying details of potential pathogenesis, course, and treatment of PLE and PB was created. The study was available online via web and Facebook portals for 1 year. Apart from 2 study-initiated posts on patient-run Facebook pages at the study initiation, all recruitment was driven by study respondents only. Response patterns and referral sources were tracked. A total of 671 respondents with a Fontan palliation completed a valid survey, including 76 who had PLE and 46 who had PB. Responses over time demonstrated periodic, marked increases as new online populations of Fontan patients were reached. Of the responses, 574 (86%) were from the United States and 97 (14%) were international. The leading referral sources were Facebook, internet forums, and traditional websites. Overall, social media outlets referred 84% of all responses, making it the dominant modality for recruiting the largest reported contemporary cohort of Fontan patients and patients who have PLE and PB. The methodology and response patterns from this study can be used to design research applications for other rare diseases.
Molina-García, Ana; Castellanos-Cosano, Lizett; Posada-de la Paz, Manuel
Background Rare diseases (RD) are those that present a lower prevalence than 5 cases per 10.000 population. The main objective of this review was to study the effect on oral health in rare diseases, while the secondary objective of the study is theme upgrade. Material and Methods Comparative observational case-control studies were analysed and a systematic review was conducted in PubMed. Each rare disease listed on the statistical data record of the Health Portal of the Ministry of Equality, Health and Social Policies Board of Andalusia was associated with “oral health”. The variables studied included dental, oral mucosa and occlusion alterations, oral pathologies (caries, periodontal disease) and other alterations (mouth breathing, parafunctional habits, etc). A bias analysis of the variable caries was conducted. Results Six RD were selected through our inclusion and exclusion criteria (hypogammaglobulinemia, Rett syndrome, Marfan syndrome, Prader-Willi syndrome, cystic fibrosis and Cri du chat syndrome) in a total of 8 publications, of which four trials were classified as high risk of bias and one of them as medium risk. There were not trials with low risk of bias. Conclusions The main statistically significant differences found by Syndrome compared to a control group were in Hypogammaglobulinemia with a greater tendency to enamel hypoplasia and dry mouth. The Rett syndrome had, as well, a greater tendency to an anterior open bite, ogival palate, bruxism, mouth breathing and tongue thrusting. Prader-Willi syndrome had a tendency of dental erosion, and Cri du chat syndrome showed a higher association to Tannerella forsythia. Key words:Rare diseases, oral health. PMID:27475682
Ferrelli, Rita Maria; Gentile, Amalia Egle; De Santis, Marta; Taruscio, Domenica
In the framework of the Joint Action for Rare Diseases (RD-ACTION), a specific task was defined to identify mechanisms influencing sustainability, equity and resilience of health systems for rare diseases (RDs). Literature narrative review on health systems sustainability and resilience for RDs. Years: 2000-2015. Databases: PubMed, Scopus, EBSCOHost, EMBAL, PASCAL, EMBASE, STN International and GoogleScholar. interpretive synthesis concept and thematic analysis (Dixon-Wood, et al.). 97 papers and 4 grey literature publications were identified. Two main topics stand out: economic evaluation and networks. The first topic did not identify widely accepted criterion to assign more weight to individuals with greater health needs. Healthcare network are identified as increasingly important for sustainability and resilience, in all of their aspects: professional "expertise", "experience" networks of users and carers; policy, learning, and interest networks. Possible mechanisms for ensuring sustainability can be identified in networking, patients' empowerment and reorienting healthcare towards integrated community and home care.
Lu, Dai-Yin; Gau, Jyh-Pyng; Hong, Ying-Chung; Liu, Chun-Yu; Yu, Yuan-Bin; Hsiao, Liang-Tsai; Liu, Jin-Hwang; Chen, Po-Min; Chiou, Tzeon-Jye; Tzeng, Cheng-Hwai
Systemic mastocytosis is characterized by pathologic proliferation and accumulation of mast cells in at least one extracutaneous organ such as liver, spleen, bone marrow, or lymph nodes. The clinical features are highly variable depending on impairment of the involved organ systems. It often raises diagnostic challenges. Here we report a case of a 78-year-old patient with mast cell leukemia. The literature is reviewed regarding the diagnosis and updated management of this rare disease.
Julia Maimone Beatrice
Full Text Available Essential thrombocythemia is an acquired myeloproliferative disorder characterized by the proliferation of megakaryocytes in bone marrow, leading to a persistent increase in the number of circulating platelets and thus increasing the risk for thrombotic and hemorrhagic events. The disease features leukocytosis, splenomegaly, vascular occlusive events, hemorrhages and vasomotor disorders. The intricate mechanisms underlying the molecular pathogenesis of this disorder are not completely understood and are still a matter of discussion. Essential thrombocythemia is an extremely rare disorder during childhood. We report on a case of essential thrombocythemia in a child and discuss the diagnostic approach and treatment strategy.
Kyasanur forest disease (KFD) is a rare tick borne zoonotic disease that causes acute febrile hemorrhagic illness in humans and monkeys especially in southern part of India. The disease is caused by highly pathogenic KFD virus (KFDV) which belongs to member of the genus Flavivirus and family Flaviviridae. The disease is transmitted to monkeys and humans by infective tick Haemaphysalisspinigera. Seasonal outbreaks are expected to occur during the months of January to June. The aim of this paper is to briefly summarize the epidemiology, mode of transmission of KFD virus, clinical findings, diagnosis, treatment, control and prevention of the disease..
Tosi, Laura L; Warman, Matthew L
Rare bone diseases account for 5% of all birth defects and can cause significant morbidity throughout patients' lives. Significant progress is being made to elucidate the pathophysiological mechanisms underlying these diseases. This paper summarizes presentation highlights of a workshop on Rare Skeletal Diseases convened to explore how the study of rare diseases has influenced the field's understanding of bone anabolism and catabolism and directed the search for new therapies benefiting patients with rare conditions as well as patients with common skeletal disorders.
Mascalzoni, Deborah; Paradiso, Angelo; Hansson, Matts
Due to the few patients affected, rare disease research has to count on international registries to exist in order to produce significant research outputs. Data sharing of registries is therefore a unique resource to allow rare disease research to flourish and any lost data will jeopardize the quality of an already extremely difficult research. The rules usually applied to research such as the right to withdraw or the need for specific consent for every use of data can be detrimental in order to get effective results. Privacy rights regulated through traditional informed consent mechanisms have been regarded as a major barrier in order to effectively share data worldwide. Some authors argue that this barrier hampers results that could be beneficial to the patients so that another right will be overstated: the right to quality healthcare. We argue in this paper that privacy has been often interpreted just one-sided as the right to secrecy but it can entail another meaning: the right to manage one's own private sphere. Managing it pertains, not only to the right to deny access, but also to the right to grant access. At the same time research on patient participation and transparency shows that new forms of IT-based informed consent can provide a good balance between the right of individuals to be in control of their data and the opportunity for science to pursue international research.
Full Text Available Due to the few patients affected, rare disease research has to count on international registries to exist in order to produce significant research outputs. Data sharing of registries is therefore a unique resource to allow rare disease research to flourish and any lost data will jeopardize the quality of an already extremely difficult research. The rules usually applied to research such as the right to withdraw or the need for specific consent for every use of data can be detrimental in order to get effective results. Privacy rights regulated through traditional informed consent mechanisms have been regarded as a major barrier in order to effectively share data worldwide. Some authors argue that this barrier hampers results that could be beneficial to the patients so that another right will be overstated: the right to quality healthcare. We argue in this paper that privacy has been often interpreted just one-sided as the right to secrecy but it can entail another meaning: the right to manage one's own private sphere. Managing it pertains, not only to the right to deny access, but also to the right to grant access. At the same time research on patient participation and transparency shows that new forms of IT-based informed consent can provide a good balance between the right of individuals to be in control of their data and the opportunity for science to pursue international research.
Sánchez Lázaro, J A; Linares Álvarez, L
Pycnodysostosis is a rare disease caused by a dysfunction of the osteoclasts due to a mutation in the cathepsin K gene. We present a case of a young adult patient with the above mentioned syndrome, who suffered an atypical fracture of the tibia after a low energy fall. Some bone changes that could have predisposed the fracture were observed when examined in the Emergency Department. Not long afterwards he suffered the same type of fracture in another tibia. Due to the conditions typical of the pycnodysostosis, the above mentioned fracture required an unconventional approach for this mid-shaft tibial fracture (osteosynthesis plate), combined with a longer consolidation time. The case was finally resolved satisfactorily. Copyright © 2013 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.
Wühl, Elke; van Stralen, Karlijn J; Wanner, Christoph
and separately for children and adults. METHODS: The Orphanet classification of rare disease was searched for rare diseases potentially causing ESRD, and these diagnosis codes were mapped to the corresponding ERA-EDTA primary renal disease codes. Thirty-one diagnoses were defined as rare diseases causing ESRD...... disease affected young patients in up to 46%. On 31 December 2011, 20 595 patients (12.4% of the total RRT population) were on RRT for ESRD caused by a rare disease. The point prevalence was 32.5 per million age-related population in children and 152.0 in adults. Only 5.8% of these patients were younger...
Kanık, Esra Toprak; Yılmaz, Özge; Türkeli, Ahmet; Şahin, Şebnem; Yüksel, Hasan
Follicular bronchiolitis (FB) is a benign progressive lung disease. It is characterized with lymphoplasmocellular infiltration and hyperplastic follicles in the peribronchial areas in the small airways. Follicular bronchiolitis should be considered in cases where chronic cough, recurrent upper respiratory tract infections and progressive dyspnea are observed in children. The diagnosis should be supported by lung biopsy. A 8-year old female patient presented to our hospital with complaints including continuing cough and wheezing. Bilateral extensive rales and rhonchi in the lungs were heard on auscultation and lung graphy revealed reticuloglandular appearance. Bilateral extensive septal thickennings, reticulonodular appearance, patchy bronchiectasis, bronchiolectasis and peribronchial thickennings were found on high-resolution thoracal computarized tomography. A diagnosis of follicular bronchiolitis was made as a result of lung biopsy. Improvement was observed in the complaints and findings of our patient after methylprednisolone treatment. This patient was presented to emphasize rare interstitial lung diseases should also be considered in children who present with a clinical picture of chronic bronchial obstruction and do not respond to standard treatment. PMID:26078687
... What's this? Submit Button Past Emails CDC Features Necrotizing Fasciitis: A Rare Disease, Especially for the Healthy Language: ... based hand rub if washing is not possible. Necrotizing Fasciitis Is Rarely Spread from Person to Person Most ...
Rajput, Neeraj Kumar; Singh, Vipin; Bhardwaj, Anshu
Over 300 million people are affected by about 7000 rare diseases globally. There are tremendous resource limitations and challenges in driving research and drug development for rare diseases. Hence, innovative approaches are needed to identify potential solutions. This review focuses on the resources developed over the past years for analysis of genome data towards understanding disease biology especially in the context of mitochondrial diseases, given that mitochondria are central to major cellular pathways and their dysfunction leads to a broad spectrum of diseases. Platforms for collaboration of research groups, clinicians and patients and the advantages of community collaborative efforts in addressing rare diseases are also discussed. The review also describes crowdsourcing and crowdfunding efforts in rare diseases research and how the upcoming initiatives for understanding disease biology including analyses of large number of genomes are also applicable to rare diseases.
Hirayama disease, also known as monomelic amyotrophy (MMA), is a rare cervical myelopathy that manifests itself as a self-limited, asymmetrical, slowly progressive atrophic weakness of the forearms and hands predominantly in young males. The forward displacement of the posterior dura of the lower cervical dural canal during neck flexion has been postulated to lead to lower cervical cord atrophy with asymmetric flattening. We report a case of Hirayama disease in a 25-year-old Indian man presenting with gradually progressive asymmetrical weakness and wasting of both hands and forearms along with unusual features of autonomic dysfunction and upper motor neuron lesion. PMID:28097028
Full Text Available Hirayama disease, also known as monomelic amyotrophy (MMA, is a rare cervical myelopathy that manifests itself as a self-limited, asymmetrical, slowly progressive atrophic weakness of the forearms and hands predominantly in young males. The forward displacement of the posterior dura of the lower cervical dural canal during neck flexion has been postulated to lead to lower cervical cord atrophy with asymmetric flattening. We report a case of Hirayama disease in a 25-year-old Indian man presenting with gradually progressive asymmetrical weakness and wasting of both hands and forearms along with unusual features of autonomic dysfunction and upper motor neuron lesion.
Anuradha, S; Fanai, Vanlalmalsawmdawngliana
Hirayama disease, also known as monomelic amyotrophy (MMA), is a rare cervical myelopathy that manifests itself as a self-limited, asymmetrical, slowly progressive atrophic weakness of the forearms and hands predominantly in young males. The forward displacement of the posterior dura of the lower cervical dural canal during neck flexion has been postulated to lead to lower cervical cord atrophy with asymmetric flattening. We report a case of Hirayama disease in a 25-year-old Indian man presenting with gradually progressive asymmetrical weakness and wasting of both hands and forearms along with unusual features of autonomic dysfunction and upper motor neuron lesion.
Gallagher, James A; Ranganath, Lakshminarayan R; Boyde, Alan
Studying severe phenotypes of rare syndromes can elucidate disease mechanisms of more common disorders and identify potential therapeutic targets. Lessons from rare bone diseases contributed to the development of the most successful class of bone active agents, the bisphosphonates. More recent research on rare bone diseases has helped elucidate key pathways and identify new targets in bone resorption and bone formation including cathepsin K and sclerostin, for which drugs are now in clinical trials. By contrast, there has been much less focus on rare cartilage diseases and osteoarthritis (OA) remains a common disease with no effective therapy. Investigation of rare cartilage syndromes is identifying new potential targets in OA including GDF5 and lubricin. Research on the arthropathy of the ultra-rare disease alkaptonuria has identified several new features of the OA phenotype, including high density mineralized protrusions (HDMPs) which constitute a newly identified mechanism of joint destruction.
Full Text Available Objective of the study was to review the anamnesis, pheno - and genotype in patients with rare chromosome disorders such as 9p deletion syndrome. Genetic methods of investigation (clinical and genealogical, cytogenetic, FISH- method, paraclinical and instrumental methods of examination were used. Karyotyping was performed by the G-method of differential staining of chromosomes. Only three cases of pathology were diagnosed in the Medical Genetics Center over the last 10 years. By anamnesis data nobody in the probands’ families had bad habits, was exposed to occupational hazards, took part in the elimination of the Chernobyl accident or lived in contaminated areas. Clinical signs of diseases have not been identified in probands’ parents. All probands had trigonocephaly, bilateral epicanthal folds, ocular hypertelorism, downslanting palpebral fissures, long philtrum, flat face and nasal bridge, low set ears with malformed auricles. Two patients of three ones had exophthalmos, contracture of the second and third fingers, abnormal external genitalia. In all three cases there was monosomy of chromosome 9 of critical segment p 24. Normal karyotypes were seen in all parents, so there were three cases of new mutations of 9p deletion syndrome. Retardation of physical, psycho-spech, mental development in proband with or without congenital anomalies requires medical genetic counseling in a specialized institution. Cases of reproductive loss in anamnesis require cytogenetic investigation of fetal membranes and amniotic fluid.
Dragusin, Radu; Petcu, Paula; Lioma, Christina;
Increasingly more clinicians use web Information Retrieval (IR) systems to assist them in diagnosing difficult medical cases, for instance rare diseases that they may not be familiar with. However, web IR systems are not necessarily optimised for this task. For instance, clinicians’ queries tend...... search and offline retrieval from a rare disease collection indicate that the retrieval of rare diseases is an open problem with room for improvement....
Federal Laboratory Consortium — NCATS collaborates with the National Human Genome Research Institute (NHGRI) to support GARD, a center designed to provide comprehensive information about rare and...
Rheumatoid Arthritis; Spondyloarthritis; Psoriatic Arthritis; Systemic Lupus Erythematosus; Antiphospholipid Syndrome; Sjogren Syndrome; Scleroderma; Myositis; Vasculitis; Mastocytosis; Various Autoimmune and/or Systemic and/or Rare Diseases
Yang, Li; Su, Chang; Lee, Ashley M; Bai, Harrison X
The Chinese researchers have made significant progress in studying rare diseases in the recent years. From 2000 to 2014, 269 out of 1892 clinically relevant original research papers published on high impact journals by Chinese institutions, and 2678 out of 6040 clinical trials conducted by Chinese institutions and registered at ClinicalTrial.gov are focused on rare diseases. The number of research papers and of clinical trials has shown a steady trend of increase. Creating public databases for rare disease will escalate progress in rare disease and enable multicenter studies.
Rodwell, Charlotte; Aymé, Ségolène
Rare diseases are those with a particularly low prevalence; in Europe, diseases are considered to be rare when they affect not more than 5 in 10000 persons in the European Union. The specificities of rare diseases make the area a veritable public health challenge: the limited number of patients and scarcity of knowledge and expertise single rare diseases out as a distinctive domain of high European added-value. The Orphan Medicinal Product Regulation of 1999 was the first European legislative text concerning rare diseases, followed by many initiatives, including recommendations by the Council of Ministers of the European Union in 2009. These initiatives contributed to the development of rare diseases policies at European and national level aimed at improving care for patients with rare diseases. A review of the political framework at European level and in European countries is provided to demonstrate how legislation has created a dynamic that is progressively improving care for patients with rare diseases. This article is part of a Special Issue entitled: "Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease)".
Rare diseases have a prevalence of lower than 5 in 10,000 inhabitants and are life-threatening or chronically debilitating. It is estimated that worldwide more than 5000 rare diseases exist, which account for over 55 million patients in the EU and the US together. However, the development of drugs
Rare diseases have a prevalence of lower than 5 in 10,000 inhabitants and are life-threatening or chronically debilitating. It is estimated that worldwide more than 5000 rare diseases exist, which account for over 55 million patients in the EU and the US together. However, the development of drugs f
Timely identification and reporting of rare infectious diseases has important economic, social and health implications. In this study, we investigate how different stakeholders in the existing reporting system influence the timeliness in identification and reporting of rare infectious diseases. Building on the vision of the information supply…
Timely identification and reporting of rare infectious diseases has important economic, social and health implications. In this study, we investigate how different stakeholders in the existing reporting system influence the timeliness in identification and reporting of rare infectious diseases. Building on the vision of the information supply…
Rance, Bastien; Snyder, Michelle; Lewis, Janine; Bodenreider, Olivier
Background Rare disease information sources are incompletely and inconsistently cross-referenced to one another, making it difficult for information seekers to navigate across them. The development of such cross-references established manually by experts is generally labor intensive and costly. Objectives To develop an automatic mapping between two of the major rare diseases information sources, GARD and Orphanet, by leveraging terminological resources, especially the UMLS. Methods We map the rare disease terms from Orphanet and ORDR to the UMLS. We use the UMLS as a pivot to bridge between the rare disease terminologies. We compare our results to a mapping obtained through manually established cross-references to OMIM. Results Our mapping has a precision of 94%, a recall of 63% and an F1-score of 76%. Our automatic mapping should help facilitate the development of more complete and consistent cross-references between GARD and Orphanet, and is applicable to other rare disease information sources as well. PMID:23920611
Full Text Available Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient’s symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80% and sensitivity (≥99%, and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers.
Piñol, Marc; Vilaplana, Jordi; Teixidó, Ivan; Cruz, Joaquim; Comas, Jorge; Vilaprinyo, Ester; Sorribas, Albert
Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient’s symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers. PMID:27547534
Alves, Rui; Piñol, Marc; Vilaplana, Jordi; Teixidó, Ivan; Cruz, Joaquim; Comas, Jorge; Vilaprinyo, Ester; Sorribas, Albert; Solsona, Francesc
Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient's symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers.
D’Agnolo, Hedwig MA; Kievit, Wietske; Andrade, Raul J; Karlsen, Tom Hemming; Wedemeyer, Heiner
The exposure of clinicians to patients with rare gastrointestinal diseases is limited. This hurts clinical studies, which impedes accumulation of scientific knowledge on the natural disease course, treatment outcomes and prognosis in these patients. An excellent method to detect patterns on an aggregate level that would not be possible to discover in individual cases, is a registry study. This paper aims to describe a template to create a successful international registry for rare diseases. We focus mainly on rare hepatic diseases, but lessons from this paper serve other fields in medicine, as well. PMID:27403298
D'Agnolo, Hedwig Ma; Kievit, Wietske; Andrade, Raul J; Karlsen, Tom Hemming; Wedemeyer, Heiner; Drenth, Joost Ph
The exposure of clinicians to patients with rare gastrointestinal diseases is limited. This hurts clinical studies, which impedes accumulation of scientific knowledge on the natural disease course, treatment outcomes and prognosis in these patients. An excellent method to detect patterns on an aggregate level that would not be possible to discover in individual cases, is a registry study. This paper aims to describe a template to create a successful international registry for rare diseases. We focus mainly on rare hepatic diseases, but lessons from this paper serve other fields in medicine, as well.
Groft, Stephen C
Extensive public-private partnerships, including the National Institutes of Health (NIH) and the rare diseases community, which is seeing a renewed industry interest in smaller niche markets, have resulted in an increase of interventions for rare diseases. Significant collaborative efforts are required among the pharmaceutical industry, foundations, patient-advocacy groups, academic and government investigators and funding programs, regulatory scientists, and reimbursement agencies to meet the unmet diagnostic and treatment needs for approximately 25 million people in the United States with 7,000 rare diseases. The expanding role and outreach activities of patient-advocacy groups have increased public awareness. In the United States, a rare disease is defined as a disorder or condition with a prevalence of $3.5 billion for rare diseases research, including $750 million for orphan product development activities, nearly 11.4% of the NIH research budget. Several research institutes and centers of the NIH, including the National Center for Advancing Translational Sciences, have initiated varied translational research efforts to address the absence of preclinical and clinical data required for regulatory review purposes. Clinicians can expect to see significant increases in requests from patients and their families to participate in patient registries and natural history or observational studies to gather specific information from a larger pool of patients on the progression of the disease or response to treatments. An expanding emphasis on rare diseases provides hope for the millions of patients with rare diseases.
Aymé, Ségolène; Rodwell, Charlotte
The European Union Committee of Experts on Rare Diseases was entrusted with aiding the European Commission in a number of tasks, ranging from the monitoring of initiatives, to recommending improvements and actions to be pursued in the future, in addition to helping strengthen liaison at both European and International levels in the field of rare diseases. The three-year mandate of the EUCERD drew to a close in July 2013 with an impressive record. The EUCERD has laid down the foundations for future work so as to continue to advance in the key areas that have been identified as of interest for the rare disease community at large: centres of expertise, European Reference Networks, patient registries and databases, newborn screening, and indicators for national rare disease plans/strategies. The work of the Committee should now be continued by the newly formed European Commission Expert Group on Rare Diseases.
Fernandez-Novo, Sara; Pazos, Florencio; Chagoyen, Monica
ODCs (Orphan Disease Connections), available at http://csbg.cnb.csic.es/odcs, is a novel resource to explore potential molecular relations between rare diseases. These molecular relations have been established through the integration of disease susceptibility genes and human protein-protein interactions. The database currently contains 54,941 relations between 3032 diseases.
Abhiram Chakrabarti; Manab Nandy; Dipankar Pal; Sudesna Mallik
Leptospirosis, a disease of protean manifestations occurs sporadically throughout the year with a peak seasonal incidence during the rainy season mimicking other febrile viral illness. In the rare case, the disease leads to renal and hepatic involvement with hemorrhage which may be associated with multisystem organ dysfunction in form of pulmonary, cardiac and central nervous system, when it is known as Weil's disease. Rarely haemorrhagic manifestations are assosciated. Early diagnosis is imp...
Full Text Available Rare disease patients too often face common problems, including the lack of access to correct diagnosis, lack of quality information on the disease, lack of scientific knowledge of the disease, inequities and difficulties in access to treatment and care. These things could be changed by implementing a comprehensive approach to rare diseases, increasing international cooperation in scientific research, by gaining and sharing scientific knowledge about and by developing tools for extracting and sharing knowledge. A significant aspect to analyze is the organization of knowledge in the biomedical field for the proper management and recovery of health information. For these purposes, the sources needed have been acquired from the Office of Rare Diseases Research, the National Organization of Rare Disorders and Orphanet, organizations that provide information to patients and physicians and facilitate the exchange of information among different actors involved in this field. The present paper shows the representation of rare diseases terms in biomedical terminologies such as MeSH, ICD-10, SNOMED CT and OMIM, leveraging the fact that these terminologies are integrated in the UMLS. At the first level, it was analyzed the overlap among sources and at a second level, the presence of rare diseases terms in target sources included in UMLS, working at the term and concept level. We found that MeSH has the best representation of rare diseases terms.Pazienti affetti da malattie rare molto spesso affrontano problemi comuni, tra cui la mancanza di accesso alla diagnosi corretta, la mancanza di informazioni di qualità sulla malattia, la mancanza di conoscenze scientifiche, e le difficoltà di accesso al trattamento e cura. Inadempienze e lacune che potrebbero essere colmate mediante l'attuazione di un approccio globale alle malattie rare, aumentando la cooperazione internazionale nella ricerca scientifica e lo sviluppo di strumenti per l'estrazione e la
Full Text Available Rare anemias encompass a large and markedly heterogeneous group of nearly 90 different conditions, mostly congenital or genetically determined, that, according to the definition of the European Commission, have a global prevalence of less than 5 per 10,000 individuals. However, the geographical distribution of several of those anemias varies considerably and thus their local prevalence may be significantly higher in certain regions...
Full Text Available We report a case of a 42-years-old woman with constipation, anemia and recurrent itch. After several investigations, celiac disease was diagnosed and a treatment with a gluten-free diet was applied with beneficial effects. Recognizing celiac disease can be difficult because some of its symptoms are similar to those of other diseases. In fact, sometimes it is confused with irritable bowel syndrome or iron-deficiency anemia or intestinal infections: as a result, celiac disease is commonly underdiagnosed or misdiagnosed. This case report is described to address the physician to a correct diagnosis of celiac disease.
Rajasimha, Harsha Karur; Shirol, Prasannakumar Basayya; Ramamoorthy, Preveen; Hegde, Madhuri; Barde, Sangeeta; Chandru, Vijay; Ravinandan, M E; Ramchandran, Ramani; Haldar, Kasturi; Lin, Jimmy C; Babar, Imran A; Girisha, Katta M; Srinivasan, Sudha; Navaneetham, Duraiswamy; Battu, Rajani; Devarakonda, Rajashree; Kini, Usha; Vijayachandra, Kinnimulki; Verma, Ishwar C
In order to address the unmet needs and create opportunities that benefit patients with rare disease in India, a group of volunteers created a not-for-profit organization named Organization for Rare Diseases India (ORDI; www.ordindia.org). ORDI plans to represent the collective voice and advocate the needs of patients with rare diseases and other stakeholders in India. The ORDI team members come from diverse backgrounds such as genetics, molecular diagnostics, drug development, bioinformatics, communications, information technology, patient advocacy and public service. ORDI builds on the lessons learned from numerous similar organizations in the USA, European Union and disease-specific rare disease foundations in India. In this review, we provide a background on the landscape of rare diseases and the organizations that are active in this area globally and in India. We discuss the unique challenges in tackling rare diseases in India, and highlight the unmet needs of the key stakeholders of rare diseases. Finally, we define the vision, mission, goals and objectives of ORDI, identify the key developments in the health care context in India and welcome community feedback and comments on our approach.
Devuyst, Olivier; Knoers, Nine V A M; Remuzzi, Giuseppe; Schaefer, Franz
At least 10% of adults and nearly all children who receive renal-replacement therapy have an inherited kidney disease. These patients rarely die when their disease progresses and can remain alive for many years because of advances in organ-replacement therapy. However, these disorders substantially decrease their quality of life and have a large effect on health-care systems. Since the kidneys regulate essential homoeostatic processes, inherited kidney disorders have multisystem complications, which add to the usual challenges for rare disorders. In this review, we discuss the nature of rare inherited kidney diseases, the challenges they pose, and opportunities from technological advances, which are well suited to target the kidney. Mechanistic insights from rare disorders are relevant for common disorders such as hypertension, kidney stones, cardiovascular disease, and progression of chronic kidney disease.
Lauková, D; Marget, I; Plutinský, J
Extrinsic allergic alveolitis (EAA), known as hypersensitive pneumonitis, causes interstitial lung involvement by inhaled antigen. The clinical presentation of the disease has been defined as acute, subacute and chronic. The most often symptoms of the acute form of the disease are flu-like symptoms, dyspnoe and cough. The progressive dyspnoe in particullary is characterized for the chronic form of EAA. Dyspnoe is worsed, if the disease is combinied with usual respiratory infection or reexposition of inhaled antigen. It seems the diagnostic definition of EAA should be easy and prevalence of EAA relative high. The disease belongs to the group of interstitial lung diseases and it is underestimated as a matter of fact. The clinic, radiographic, laboratory and histologic abnormalities are results of inhaled antigen contact and support the diagnosis of EAA. Specific IgG antibodies against the offending antigen along with them are consedered to be detected (established) of EAA.
Dragusin, Radu; Petcu, Paula; Lioma, Christina;
Increasingly more clinicians use web Information Retrieval (IR) systems to assist them in diagnosing difficult medical cases, for instance rare diseases that they may not be familiar with. However, web IR systems are not necessarily optimised for this task. For instance, clinicians’ queries tend...... to be long lists of symptoms, often containing phrases, whereas web IR systems typically expect very short keyword-based queries. Motivated by such differences, this work uses a preliminary study of 30 clinical cases to reflect on rare disease retrieval as an IR task. Initial experiments using both Google...... web search and offline retrieval from a rare disease collection indicate that the retrieval of rare diseases is an open problem with room for improvement....
Saint Pierre, Aude; Génin, Emmanuelle
Genome-wide association studies have uncovered hundreds of common genetic variants involved in complex diseases. However, for most complex diseases, these common genetic variants only marginally contribute to disease susceptibility. It is now argued that rare variants located in different genes could in fact play a more important role in disease susceptibility than common variants. These rare genetic variants were not captured by genome-wide association studies using single nucleotide polymorphism-chips but with the advent of next-generation sequencing technologies, they have become detectable. It is now possible to study their contribution to common disease by resequencing samples of cases and controls or by using new genotyping exome arrays that cover rare alleles. In this review, we address the question of the contribution of rare variants in common disease by taking the examples of different diseases for which some resequencing studies have already been performed, and by summarizing the results of simulation studies conducted so far to investigate the genetic architecture of complex traits in human. So far, empirical data have not allowed the exclusion of many models except the most extreme ones involving only a small number of rare variants with large effects contributing to complex disease. To unravel the genetic architecture of complex disease, case-control data will not be sufficient, and alternative study designs need to be proposed together with methodological developments.
Full Text Available Primary thyroid lymphomas are rare neoplasms comprising of 1-5% of thyroid malignancies. These are predominantly B-cell in origin. Here, we report a case of 60 years lady, a known case of lymphocytic thyroiditis, diagnosed as thyroid lymphoma (diffuse large B-cell on fine needle aspiration and confirmed histopathogically and immunohistochemically. She presented with a sudden increase in thyroid swelling. Fine needle aspiration performed showed highly cellular smears comprising predominantly of the monomorphic population of medium to large sized lymphoid cells with high nuclear/cytoplasmic ratio and scant cytoplasm. A possibility of thyroid lymphoma possibly diffuse large B-cell lymphoma was suggested which was later confirmed on biopsy. Fine needle aspiration provides an easy mode for diagnosing large cell lymphoma like diffuse large B-cell. Hence, an early diagnosis is possible for a timely intervention. Also, cases of lymphocytic thyroiditis should be regularly followed for the development of lymphoma.
The authors present a survey of 50 documented cases of metabolic lactic acidosis (MLAC) recorded in the course of 5 years. To this study cases of severe hyperlactataemia (determined minimum lactate level of concentration 4 mmol/l) have been included. The sample consists of patients hospitalized at the Department of Internal Medicine Litomĕrice (hinterland of about 110,000 inhabitants). Liver involvement in 5 cases, cardiogenous shock in 6 cases, sepsis in 2 cases were the cause of lactic acidosis. The administration of biguanids (Adebit, Silubin R, Diformin) seems to be the probable cause in 21 cases, other cases were triggered by rarer causes. Dehydratation (16), vomiting (9), diarrhoea (11) dominate often in the clinical picture. The patients were admitted to the hospital often unconscious, with diagnose of vasculo-cerebral incidence, transitory ischaemic incidence... Quit rarely the typical Kussmaul's respiratory (only 9 cases) was recorded. Hyperlactatemia was usually associated with decrease of blood pH (theta = 7.12, pH less than 7.35 was recorded in 49 cases, pH less than 6.8 in 5 cases) and with decrease of BE value (= Ccoase, theta = -15.3 mmol/l). When the hypochloremia and/or hypocapnia was simultaneously more severe, only in these cases the value of pH was within physiological limits or even increased (10). The conclusions show that MLAC is not a rare disorder, however, its occurrence is depended rather on the clinician's capacity to diagnose this disorder and to indicate lactate examination. Usual signs of acidosis (Kussmaul's respiratory, decrease of pH, decrease of BE) can be missing in many cases.(ABSTRACT TRUNCATED AT 250 WORDS)
The internet, and social media platforms, are increasingly being used by substantial sectors of the worldwide population. By engaging effectively with online and social media, scientists and clinicians can obtain unprecedented access to relatively large cohorts of individuals with rare diseases, as well as their relatives, carers and professionals involved in their healthcare. Online surveys of these stakeholder groups may provide important new insights into rare conditions and their management relatively quickly and easily, with the possibility of rapid translation into healthcare interventions and policy. Here, I describe our recent positive experience with the online survey approach to a rare disease (X-linked ichthyosis), and review its advantages and limitations.
Full Text Available Moyamoya disease is a rare, chronic cerebrovascular occlusive disease of unknown etiology. It is characterized by progressive stenosis of the arteries of the circle of Willis leading to ischemicstrokes in young people and cerebral hemorrhage, which is more frequent in adults. Secondarily,an abnormal network of fine collateral vessels arises at the base of the brain. The term moyamoyarefers to the angiographic appearance of the cerebral vasculature. We present such a disease in an 18-month-old Iranian girl with global developmental delay, which is a very rare presentationof moyamoya disease. She was diagnosed by magnetic resonance imaging (MRI and magnetic resonance angiography (MRA.
Fernandez Cabo, Jose Luis; Lucia Cermeño, María; Conde Gomez, Ruben; Antuña Bernardo, Joaquín; Majano Majano, María Almudena
Se van a trazar los diagramas de esfuerzos normales, cortantes y flectores (o simplemente diagramas de esfuerzos) de estructuras relativamente simples, y además en orden creciente de complejidad. Los comentarios y explicaciones serán por ello mayores y de aspectos más básicos al comienzo, y poco a poco se irá atendiendo a cuestiones más complejas. Se recomienda por ello que el alumno lea este documento en el orden que está escrito. Se tratará sólo el caso de estructuras isostáticas, de modo q...
Se van a trazar los diagramas de esfuerzos normales, cortantes y flectores (o simplemente diagramas de esfuerzos) de estructuras relativamente simples, y además en orden creciente de complejidad. Los comentarios y explicaciones serán por ello mayores y de aspectos más básicos al comienzo, y poco a poco se irá atendiendo a cuestiones más complejas. Se recomienda por ello que el alumno lea este documento en el orden que está escrito. Se tratará sólo el caso de estructuras isostáticas, de modo q...
Cubellis, Maria Vittoria; Baaden, Marc; Andreotti, Giuseppina
Many mutations responsible of Fabry disease destabilize lysosomal alpha-galactosidase, but retain the enzymatic activity. These mutations are associated to a milder phenotype and are potentially curable with a pharmacological therapy either with chaperones or with drugs that modulate proteostasis. We demonstrate the effectiveness of molecular dynamics simulations to correlate the genotype to the severity of the disease. We studied the relation between protein flexibility and residual enzymatic activity of pathological missense mutants in the cell. We found that mutations occurring at flexible sites are likely to retain activity in vivo. The usefulness of molecular dynamics for diagnostic purposes is not limited to lysosomal galactosidase because destabilizing mutations are widely encountered in other proteins, too, and represent a large share of all the ones associated to human diseases. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
Dulcinea Maria Barbosa Campos
Full Text Available Lagochilascariasis is a parasitic disease caused by a helminth of the order Ascaroidea, genus Lagochilascaris that comprises 6 species, among which only Lagochilascaris minor Leiper, 1909, is implicated in the human form of the disease. It is remarkable that the majority of cases of human lagochilascariasis in the Americas have been reported in Brazil. The natural definitive hosts of this parasite seem to be wild felines and canines. Lagochilascariasis is mostly a chronic human disease that can persist for several years, in which the parasite burrows into the subcutaneous tissues of the neck, paranasal sinuses, and mastoid. L. minor exhibits remarkable ability to migrate through the tissues of its hosts, destroying even bone tissue. Fatal cases have been described in which the parasite was found in the lungs or central nervous system. Treatment is often palliative, with recurrence of lesions. This paper summarizes the main features of the disease and its etiologic agent, including prevalence, life cycle, clinical course, and treatment.
The current status of the use of biological medicine in the treatment of adult onset morbus still, Wegeners granulomatosis and systemic lupus erythematosus (SLE) is reviewed. The need for controlled trials is emphasized. Anti-CD20 treatment for SLE patients with kidney involvement and patients wi...... with Wegeners granulomatosis seems promising. Anti-TNF and IL1 receptor antagonist can control disease activity in most patients with adult morbus still Udgivelsesdato: 2008/6/9...
Wencker, M; Teschler, H; Vogelmeier, C; Koczulla, R
The importance of rare disease is appreciated by all parties and tremendous effort is made to increase the knowledge about the individual disorders and improve the care of affected patients. Political initiatives on a European level aim to improve the structure of medical care for patients with rare diseases in each member state. The provided incentives for the development of medicines for orphan diseases have led to increased research activities and numbers of licensed Orphan Drugs. Patients are organized nationally and internationally in various patient organizations and umbrella organizations. They are involved in health care policy, support the detection and research of rare diseases and offer support to affected patients and families with educational meetings and materials as well as options for discussions. Many experts are engaged in national and international networks and registries that generate and publish high quality research data on rare diseases. A well developed infrastructure is in place to support the search for qualified partners that can be of assistance with specific questions in a rare lung disease.
Rubinstein, Yaffa R; Groft, Stephen C; Bartek, Ronald; Brown, Kyle; Christensen, Ronald A; Collier, Elaine; Farber, Amy; Farmer, Jennifer; Ferguson, John H; Forrest, Christopher B; Lockhart, Nicole C; McCurdy, Kate R; Moore, Helen; Pollen, Geraldine B; Richesson, Rachel; Miller, Vanessa Rangel; Hull, Sara; Vaught, Jim
A movement to create a global patient registry for as many as 7,000 rare diseases was launched at a workshop, "Advancing Rare Disease Research: The Intersection of Patient Registries, Biospecimen Repositories, and Clinical Data." http://rarediseases.info.nih.gov/PATIENT_REGISTRIES_WORKSHOP/. The workshop was sponsored by the Office of Rare Diseases Research (ORDR). The focus was the building of an infrastructure for an internet-based global registry linking to biorepositories. Such a registry would serve the patients, investigators, and drug companies. To aid researchers the participants suggested the creation of a centralized database of biorepositories for rare biospecimens (RD-HUB)http://biospecimens.ordr.info.nih.gov/ that could be linked to the registry. Over two days of presentations and breakout sessions, several hundred attendees discussed government rules and regulations concerning privacy and patients' rights and the nature and scope of data to be entered into a central registry as well as concerns about how to validate patient and clinician-entered data to ensure data accuracy. Mechanisms for aggregating data from existing registries were also discussed. The attendees identified registry best practices, model coding systems, international systems for recruiting patients into clinical trials and novel ways of using the internet directly to invite participation in research. They also speculated about who would bear ultimate responsibility for the informatics in the registry and who would have access to the information. Hurdles associated with biospecimen collection and how to overcome them were detailed. The development of the recommendations was, in itself, an indication of the commitment of the rare disease community as never before.
Full Text Available Galli-Galli disease is a rare acantholytic variant of Dowling-Degos disease, with few cases reported in the literature. We describe a case of Galli-Galli disease and review the literature.
Addison's disease is a rare condition. Its onset of symptoms most often is nonspecific contributing to a diagnostic and therapeutic delay. Acute renal failure can be the first manifestation of this disease. We report the case of a patient with Addison's disease who was initially treated for acute renal failure due to multiple myeloma and whose diagnosis was adjusted thereafter. Patient's condition dramatically improved after treatment with intravenous rehydration; injectable hydrocortisone.
Bogaerts, Jan; Sydes, Matthew R.; Keat, Nicola; McConnell, Andrea; Benson, Al; Ho, Alan; Roth, Arnaud; Fortpied, Catherine; Eng, Cathy; Peckitt, Clare; Coens, Corneel; Pettaway, Curtis; Arnold, Dirk; Hall, Emma; Marshall, Ernie; Sclafani, Francesco; Hatcher, Helen; Earl, Helena; Ray-Coquard, Isabelle; Paul, James; Blay, Jean-Yves; Whelan, Jeremy; Panageas, Kathy; Wheatley, Keith; Harrington, Kevin; Licitra, Lisa; Billingham, Lucinda; Hensley, Martee; McCabe, Martin; Patel, Poulam M.; Carvajal, Richard; Wilson, Richard; Glynne-Jones, Rob; McWilliams, Rob; Leyvraz, Serge; Rao, Sheela; Nicholson, Steve; Filiaci, Virginia; Negrouk, Anastassia; Lacombe, Denis; Dupont, Elisabeth; Pauporté, Iris; Welch, John J.; Law, Kate; Trimble, Ted; Seymour, Matthew
Background The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. Settings The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional – usually randomised – clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed. Results The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design. Interpretation Trials can be designed using a wide array of possibilities. There is no ‘one size fits all’ solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases. PMID:25542058
Philippakis, Anthony A; Azzariti, Danielle R; Beltran, Sergi; Brookes, Anthony J; Brownstein, Catherine A; Brudno, Michael; Brunner, Han G; Buske, Orion J; Carey, Knox; Doll, Cassie; Dumitriu, Sergiu; Dyke, Stephanie O M; den Dunnen, Johan T; Firth, Helen V; Gibbs, Richard A; Girdea, Marta; Gonzalez, Michael; Haendel, Melissa A; Hamosh, Ada; Holm, Ingrid A; Huang, Lijia; Hurles, Matthew E; Hutton, Ben; Krier, Joel B; Misyura, Andriy; Mungall, Christopher J; Paschall, Justin; Paten, Benedict; Robinson, Peter N; Schiettecatte, François; Sobreira, Nara L; Swaminathan, Ganesh J; Taschner, Peter E; Terry, Sharon F; Washington, Nicole L; Züchner, Stephan; Boycott, Kym M; Rehm, Heidi L
There are few better examples of the need for data sharing than in the rare disease community, where patients, physicians, and researchers must search for "the needle in a haystack" to uncover rare, novel causes of disease within the genome. Impeding the pace of discovery has been the existence of many small siloed datasets within individual research or clinical laboratory databases and/or disease-specific organizations, hoping for serendipitous occasions when two distant investigators happen to learn they have a rare phenotype in common and can "match" these cases to build evidence for causality. However, serendipity has never proven to be a reliable or scalable approach in science. As such, the Matchmaker Exchange (MME) was launched to provide a robust and systematic approach to rare disease gene discovery through the creation of a federated network connecting databases of genotypes and rare phenotypes using a common application programming interface (API). The core building blocks of the MME have been defined and assembled. Three MME services have now been connected through the API and are available for community use. Additional databases that support internal matching are anticipated to join the MME network as it continues to grow.
Chakrabarti, Abhiram; Nandy, Manab; Pal, Dipankar; Mallik, Sudesna
Leptospirosis, a disease of protean manifestations occurs sporadically throughout the year with a peak seasonal incidence during the rainy season mimicking other febrile viral illness. In the rare case, the disease leads to renal and hepatic involvement with hemorrhage which may be associated with multisystem organ dysfunction in form of pulmonary, cardiac and central nervous system, when it is known as Weil's disease. Rarely haemorrhagic manifestations are assosciated. Early diagnosis is important as sometimes the disease may be life threatening. Proper antibiotics results in dramatic improvement. We hereby presented a case that had clinical features of Weil's disease with cough, dyspnoea and haemoptysis. Leptospirosis was detected on ELISA testing. Patient was cured rapidly with antibiotics. PMID:25183149
Full Text Available Leptospirosis, a disease of protean manifestations occurs sporadically throughout the year with a peak seasonal incidence during the rainy season mimicking other febrile viral illness. In the rare case, the disease leads to renal and hepatic involvement with hemorrhage which may be associated with multisystem organ dysfunction in form of pulmonary, cardiac and central nervous system, when it is known as Weil's disease. Rarely haemorrhagic manifestations are assosciated. Early diagnosis is important as sometimes the disease may be life threatening. Proper antibiotics results in dramatic improvement. We hereby presented a case that had clinical features of Weil's disease with cough, dyspnoea and haemoptysis. Leptospirosis was detected on ELISA testing. Patient was cured rapidly with antibiotics.
Socha, P.; Vajro, P.; Lefeber, D.J.; Adamowicz, M.; Tanner, S.
Pediatric hepatology appears to be a very specific field of paediatrics which deals mainly with rare diseases although clinical features can be commonly found - like increased activity of transaminases. Some of these rare diseases like Wilson disease are commonly looked for and recently Wilsonian li
Rare Disorders; Undiagnosed Disorders; Disorders of Unknown Prevalence; Cornelia De Lange Syndrome; Prenatal Benign Hypophosphatasia; Perinatal Lethal Hypophosphatasia; Odontohypophosphatasia; Adult Hypophosphatasia; Childhood-onset Hypophosphatasia; Infantile Hypophosphatasia; Hypophosphatasia; Kabuki Syndrome; Bohring-Opitz Syndrome; Narcolepsy Without Cataplexy; Narcolepsy-cataplexy; Hypersomnolence Disorder; Idiopathic Hypersomnia Without Long Sleep Time; Idiopathic Hypersomnia With Long Sleep Time; Idiopathic Hypersomnia; Kleine-Levin Syndrome; Kawasaki Disease; Leiomyosarcoma; Leiomyosarcoma of the Corpus Uteri; Leiomyosarcoma of the Cervix Uteri; Leiomyosarcoma of Small Intestine; Acquired Myasthenia Gravis; Addison Disease; Hyperacusis (Hyperacousis); Juvenile Myasthenia Gravis; Transient Neonatal Myasthenia Gravis; Williams Syndrome; Lyme Disease; Myasthenia Gravis; Marinesco Sjogren Syndrome(Marinesco-Sjogren Syndrome); Isolated Klippel-Feil Syndrome; Frasier Syndrome; Denys-Drash Syndrome; Beckwith-Wiedemann Syndrome; Emanuel Syndrome; Isolated Aniridia; Beckwith-Wiedemann Syndrome Due to Paternal Uniparental Disomy of Chromosome 11; Beckwith-Wiedemann Syndrome Due to Imprinting Defect of 11p15; Beckwith-Wiedemann Syndrome Due to 11p15 Translocation/Inversion; Beckwith-Wiedemann Syndrome Due to 11p15 Microduplication; Beckwith-Wiedemann Syndrome Due to 11p15 Microdeletion; Axenfeld-Rieger Syndrome; Aniridia-intellectual Disability Syndrome; Aniridia - Renal Agenesis - Psychomotor Retardation; Aniridia - Ptosis - Intellectual Disability - Familial Obesity; Aniridia - Cerebellar Ataxia - Intellectual Disability; Aniridia - Absent Patella; Aniridia; Peters Anomaly - Cataract; Peters Anomaly; Potocki-Shaffer Syndrome; Silver-Russell Syndrome Due to Maternal Uniparental Disomy of Chromosome 11; Silver-Russell Syndrome Due to Imprinting Defect of 11p15; Silver-Russell Syndrome Due to 11p15 Microduplication; Syndromic Aniridia; WAGR Syndrome; Wolf
Full Text Available Sarcoidosis is a multisystem granulomatous disorder of unknown etiology and it may rarely be associated with a second disorder. Celiac disease is an immune-mediated enteropathy characterized with malabsorption caused by gluten intolerance, and several reports indicate an association between celiac disease and sarcoidosis. In addition, although celiac disease is associated with several extraintestinal pathologies, venous thrombosis has been rarely reported. Herein we present a rare case report of a patient with a diagnosis of sarcoidosis, celiac disease and deep venous thrombosis because of the rare association of these disorders. The patient was admitted with abdominal pain, weight loss, chronic diarrhea and a 5-day history of swelling in her right leg. A diagnosis of deep venous thrombosis was achieved by doppler ultrasonographic examination. The diagnosis of celiac disease was made by biopsy of duodenal mucosa and supported with elevated serum level of anti-gliadin IgA and IgG, and a diagnosis of sarcoidosis was achieved by transbronchial needle aspiration from the subcarinal lymph node during flexible bronchoscopy.
Castillo-Esparcia, Antonio; López-Villafranca, Paloma
The current study focuses on communication strategies employed by rare disease patient organizations. The aims of these organizations are: educate and inform the public about rare diseases, raise awareness of the problems related to rare diseases, and achieve social legitimacy in order give visibility to their demands. We analyzed the portrayal of rare disease and patient organizations by Spain's major media organizations in terms of circulation and viewership - the press (El País, El Mundo, La Vanguardia,ABC and El Periódico), radio (CadenaSer, Onda Cero, Cope and RNE), and television (Telecinco, Antena 3, La 1, La Sexta, Cuatro) -between 2012 and 2014.We then carried out a descriptive analysis of communication activities performed via the World Wide Web and social networks by 143 national organizations. Finally, we conducted a telephone questionnaire of a representative sample of 90 organizations in order to explore the association between media presence and funding and public image. The triangulation of quantitative and qualitative methods allowed us to meet the study's objectives. Increased visibility of the organizations afforded by an increase in the coverage of the topic by the medialed to an increase in membership - but not in donations - and increased awareness of these diseases.
Shen, Tony; Lee, Ariel; Shen, Carol; Lin, C Jimmy
There are an estimated 6000-8000 rare Mendelian diseases that collectively affect 30 million individuals in the United States. The low incidence and prevalence of these diseases present significant challenges to improving diagnostics and treatments. Next-generation sequencing (NGS) technologies have revolutionized research of rare diseases. This article will first comment on the effectiveness of NGS through the lens of long-tailed economics. We then provide an overview of recent developments and challenges of NGS-based research on rare diseases. As the quality of NGS studies improve and the cost of sequencing decreases, NGS will continue to make a significant impact on the study of rare diseases moving forward.
Taslakian, Bedros; Darwish, Houssein
Hydatid disease (echinococcosis) is a worldwide zoonosis produced by the larval stage of the Echinococcus tapeworm. The disease is endemic in many parts of the world, particularly in the Middle East, Australia, New Zealand, South America and central and south Europe. Intracranial hydatid disease is considered a rare disease and may be sometimes very difficult to diagnose based on the clinical and laboratory findings. Therefore, it is important to be aware of the condition and the imaging findings even in the non-endemic parts of the world. We report the case of a 12-year-old boy who presented with headache and vomiting for a few months. The mass was totally excised, with no postoperative complications. We present MR spectroscopy (MRS) findings in this operatively proven case of hydatid cyst of the brain. We discuss imaging findings, in particular the findings on MRS, which is rarely reported in the literature.
Patients with suspected or diagnosed rare diseases face challenges. Their own physicians usually do not have a large experience in a particular rare disease, specialists may not be easily accessible, and medical knowledge on rare diseases is either not readily available or too general to be applied to the patients' individual situations. As a specialist with experience in pheochromocytoma, I therefore started a blog to disseminate knowledge about the tumour and to discuss readers' questions about it (http://drpheo.blogspot.com/). Between 2009 and 2014, the blog was viewed 81,223 times and received 1286 comments during the 5-year period. About half of the comments contained mostly questions (questioning comments), including 429 directly on pheochromocytoma (7.5/month). The majority of the questioning comments were about the diagnosis (62%) and natural history (21%) of pheochromocytoma, with the remainder on management (14%) and follow-up or prognosis (4%). Many readers' comments started with encouraging words about the blog and remarked how difficult it was to find useful information on pheochromocytoma elsewhere. Experience with the Dr Pheo Blog suggests that physician specialist-written blogs are potentially an effective and convenient way of providing pertinent knowledge on rare diseases to the public. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Otu, Akaninyene Asuquo; Anikwe, Jude Chinedu; Cocker, Derek
Key Clinical Message While rare, Fahr's disease should be considered as a differential diagnosis for seizures, movement disorders, or cognitive impairment in tropical settings. Classically, bilateral calcification of the basal ganglia is seen on CT. Endemic infections, metabolic, and toxic causes should be excluded. Treatment using Levodopa is often beneficial. PMID:26509011
Holst, Anders Gaarsdal; Tfelt-Hansen, 1jacob; Olesen, Morten S
Catecholaminergic polymorphic ventricular tachycardia is a rare inherited heart disease, which can lead to life-threatening ventricular arrhythmias in patients with a structurally normal heart. The age of onset is usually between two and 12 years and the initial symptom is frequently syncope...
Dragusin, Radu; Petcu, Paula; Lioma, Christina
Increasingly more clinicians use web Information Retrieval (IR) systems to assist them in diagnosing difficult medical cases, for instance rare diseases that they may not be familiar with. However, web IR systems are not necessarily optimised for this task. For instance, clinicians’ queries tend...
Jones, Sheila Dove; Miller, Cynthia Dieterich
The paper reports on studies involving children having the rare chronic skin diseases of hemangiomas and epidermolysis bullosa (characterized by easy blistering). One study compared the self-concept and psychosocial development of young (mean age 46 months) children (N=19) with hemangiomas with 19 children without hemangiomas. Findings indicated…
Feltmate, Karen; Janiszewski, Peter M; Gingerich, Sheena; Cloutier, Michael
The development and commercialization of drugs for rare diseases, termed 'orphan drugs', has historically been economically unattractive. However, because of the introduction of legislation that provides financial and regulatory incentives for the development of orphan drugs, new developments are making their way through the regulatory approval processes. Unfortunately, delays in availability of new drugs for treating rare disease continue to persist. This paper reviews the approach of several regulatory jurisdictions to orphan drugs in an effort to determine their relative effectiveness in providing patient access. Generally speaking, regulatory authorities across jurisdictions have recognized the need to enhance timely access to safe, effective treatment for patients with rare diseases and have been able to shift the approval timelines for access to new care. The greater impediment to orphan drug access appears to be funding, particularly in publicly sponsored health-care systems. Redundancies in federal and provincial reviews of orphan drugs can result in significant delays in access to new drugs. Clearly, more must be done to accelerate access to the treatments so desperately needed by patients. Public payers must be held accountable for their process and decisions--especially for rare disease therapies.
Jones, Sheila Dove; Miller, Cynthia Dieterich
The paper reports on studies involving children having the rare chronic skin diseases of hemangiomas and epidermolysis bullosa (characterized by easy blistering). One study compared the self-concept and psychosocial development of young (mean age 46 months) children (N=19) with hemangiomas with 19 children without hemangiomas. Findings indicated…
慕康国; 张文吉; 崔建宇; 张福锁; 胡林
Agricultural application of rare earth (RE) has been generalized for several decades, and it is involved in crops, vegetables and stock raising in China. However, all the researches on RE mainly focus on the fields such as plant physiological activity, physiological and biochemical mechanism, sanitation toxicology and environmental security. Plant protection by using RE and the induced resistance of plant against diseases were summarized. The mechanism of rare earth against plant disease is highlighted, which includes following two aspects. First, RE elements can control some phytopathogen directly and reduce its virulence to host plant. Another possibility is that RE elements can affect host plant and induce the plant to produce some resistance to disease.
Sigvald Bernhard Refsum (1907-91) was an outstanding Norwegian neurologist, highly respected and recognised both nationally and internationally. His main scientific achievement was that he by clinical means singled out a previously unknown disease entity in the multitude of different neurodegenerative features. In his monograph from 1946 he named the disease "heredopathia atactica polyneuritiformis"; however, it was rapidly known as Refsum's disease. Twenty years later, two German scientists, Klenk and Kahlke, detected large amounts of a peculiar branched-chain fatty acid, phytanic acid, in a Refsum patient. This started an amazing revelation of the biochemical background of the disease, and also led to a logical and effective treatment. Although Refsum's disease is extremely rare, it has become well-known due to this elucidation of both the normal metabolism of phytanic acid and the pathophysiology of the disease.
John M Conly
Full Text Available Knowledge about Whipple's disease began to emerge in 1907, when George Hoyt Whipple recognized the first case of the disease that now bears his name. He reported the case of a 36-year-old physician with "a gradual loss of weight and strength, stools consisting chiefly of neutral fat and fatty acids, indefinite abdominal signs, and a peculiar multiple arthritis" (1. Findings at autopsy consisted of poly-serositis, aortic valve vegetations and deposition of fat in the intestinal mucosa and regional lymph nodes with marked infiltration by foamy macrophages (1. It was originally thought to be a disorder of fat metabolism, and the term 'intestinal lipodystrophy' was proposed. Whipple's disease has since been recognized as a rare, multivisceral, chronic disease with a clinical presentation dominated by a symptom triad of diarrhea, weight loss and malabsorption. However, digestive symptoms are often preceded for months or years by other symptoms, the most common being arthralgia, although cardiovascular, neurological or pulmonary involvement may be more prominent at times. Once considered the ideal case report, recent characterization of Tropheryma whippelii by means of broad range bacterial ribosomal DNA polymerase chain reaction (PCR analysis (2,3 and its subsequent cultivation (4 has led to a veritable explosion of individual case reports, case series and hitherto unrecognized manifestations of the disease, such that it is now considered an underdiagnosed infectious disease (5. It is timely to provide an update on new developments in Whipple's disease.
Rudolf, Volker H W; Antonovics, Janis
Cannibalism has been documented as a possible disease transmission route in several species, including humans. However, the dynamics resulting from this type of disease transmission are not well understood. Using a theoretical model, we explore how cannibalism (i.e. killing and consumption of dead conspecifics) and intraspecific necrophagy (i.e. consumption of dead conspecifics) affect host-pathogen dynamics. We show that group cannibalism, i.e. shared consumption of victims, is a necessary condition for disease spread by cannibalism in the absence of alternative transmission modes. Thus, endemic diseases transmitted predominantly by cannibalism are likely to be rare, except in social organisms that share conspecific prey. These results are consistent with a review of the literature showing that diseases transmitted by cannibalism are infrequent in animals, even though both cannibalism and trophic transmission are very common.
Cardoso, Fernanda; Serafini, Natália Battisti; Reis, Brisa Dondoni; Nuñez, Mónica Daniela Gauto; Nery, José Augusto da Costa; Lupi, Omar
Generalized eruptive histiocytoma is considered an extremely rare subtype of non-Langerhans cells histiocytosis. In the literature, there are few reports of this disease that mainly affects adults. In this report, we present a case of generalized eruptive histiocytoma in an elderly patient who had presented symptoms for over two months. Multiple erythematous papules, asymptomatic and symmetrically distributed were observed on the trunk and limbs. Histological examination showed a dense mononuclear cell dermal infiltrate. In the immunohistochemical analysis, the cells were CD68 positive, but CD1a, S100 and CD34 negative. A diagnosis of generalized eruptive histiocytoma was established. The aim of our paper is to report a case of a very rare disease, whose subtype and affected age group are even more unusual. PMID:23539013
Full Text Available The present article reports the case of a 22-yr-old female with new onset Crohn's colitis, anterior uveitis and multiple pulmonary nodules which, on histological examination, were necrobiotic nodules. This is a rare but recognised pulmonary extraintestinal manifestation of Crohn's disease and only the fourth reported case. The present case report is followed by a brief review of the relevant literature.
Segal, B.H.; Veys, P.; Malech, H; Cowan, M. J.
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency with x-linked or autosomal recessive inheritance involving defects in genes encoding phox proteins which are the subunits of the phagocyte NADPH oxidase. This results in failure to produce superoxide anion and downstream antimicrobial oxidant metabolites and to activate antimicrobial proteases. Affected patients are susceptible to severe, life-threatening bacterial and fungal infections and excessive inflammation character...
Malinescu, Bogdan; Martius, Eliza; Pelin, Ana Maria
Peroxisomal diseases are rare (1:50,000), genetically determined disorders (autosomal recessive), systemic, multiorgan illnesses with prominent involvement of the nervous system, caused either by the failure to form or to maintain the peroxisome, or by a defect in the function of a single or multiple peroxisomal enzymes. Peroxisomes contain approximately 50 enzymes which are responsible for many metabolic reactions, and play an important role in the oxidation of saturated very-long-chain fatty acids (VLCFA). The authors present the case of a Romanian boy, who died at the age of 1.6 of one of the peroxisomal diseases-Zellweger syndrome. Newborn infants with Zellweger syndrome have a typical dysmorphic facies, neonatal seizures, profound hypotonia, and eye abnormalities. Major abnormalities are present in the liver (fibrotic), kidney (cortical cysts), and brain (lipid-laden macrophages and histiocytes in cortical and periventricular areas, demyelination, centrosylvian polymicrogyria and pachygyria)-cerebro-hepato-renal syndrome (CHRS) (Zellweger). Infants with Zellweger syndrome rarely live more than a few months, but in this case the survival was longer, and the cause of death was not directly the peroxisomal disease but a violent cause of death-mechanical asphyxia with tracheo-bronchial food aspiration. The authors present the results of investigations carried out during the child's life, but also data collected at the autopsy and hystopathological postnecroptic investigations. By presenting this case, the authors wish to bring to your attention a rare pathology in forensic practice by the paradox of finding a common violent cause of death, asphyxia with food aspiration, in a rare metabolic-genetic disease, which is usually fatal by itself.
Full Text Available Epidermolysis bullosa is a congenital and herediter vesiculobullous disease. Dystrophic form of this disease is characterized by severe malnutrition, failure to thrive, adhesions at fingers, joint contractures related with the formation of scar tissues, carcinoma of the skin, anemia, hipoalbuminemia, wound enfections and sepsis. Rarely, mortal dilated cardiomyopathy may occur in patients. In this report we present a 13 year-old pediatric patient with dilated cardiomyopathy, clinically diagnosed with Epidermolysis bullosa as well as a review of recent related literature.
Stephen C Juvet
Full Text Available Pulmonary Langerhans’ cell histiocytosis (PLCH is an unusual cystic lung disease that is also characterized by extrapulmonary manifestations. The current review discusses the presenting features and relevant diagnostic testing and treatment options for PLCH in the context of a clinical case. While the focus of the present article is adult PLCH and its pulmonary manifestations, it is important for clinicians to distinguish the adult and pediatric forms of the disease, as well as to be alert for possible extrapulmonary complications. A major theme of the current series of articles on rare lung diseases has been the translation of insights gained from fundamental research to the clinic. Accordingly, the understanding of dendritic cell biology in this disease has led to important advances in the care of patients with PLCH.
Weber, D J; Rutala, W A
Americans are increasingly exposed to exotic zoonotic diseases through travel, contact with exotic pets, occupational exposure, and leisure pursuits. Appropriate isolation precautions are required to prevent nosocomial transmission of rare zoonotic diseases for which person-to-person transmission has been documented. This minireview provides guidelines for the isolation of patients and management of staff exposed to the following infectious diseases with documented person-to-person transmission: Andes hantavirus disease, anthrax, B virus infection, hemorrhagic fevers (due to Ebola, Marburg, Lassa, Crimean-Congo hemorrhagic fever, Argentine hemorrhagic fever, and Bolivian hemorrhagic fever viruses), monkeypox, plague, Q fever, and rabies. Several of these infections may also be encountered as bioterrorism hazards (i.e., anthrax, hemorrhagic fever viruses, plague, and Q fever). Adherence to recommended isolation precautions will allow for proper patient care while protecting the health care workers who provide care to patients with known or suspected zoonotic infections capable of nosocomial transmission.
Full Text Available A case of extensive ossification around the left hip joint involving lesser trochanter of the femur leading to ankylosis of left hip joint in a 60 years male is being reported. The diagnosis of moyamoya disease was made , which is a rare form of occlusive cerebrovasc ular disorder. Occlusion of an artery may present with Transient Ischemic Attacks , headaches , stroke and seizures. Surgical management is the only option in these cases. This 60 years male had an acute onset hemiplegia 4 ½ years back and at present came wit h complaints of pain and swelling over the left hip. Surgical excision was done and histopathological examination revealed extensive ossification of skeletal muscle. A diagnosis of Moyamoya disease complicated with heterotopic ossification was made. There was no recurrence after 8 months of follow up.
Song, Peipei; He, Jiangjiang; Li, Fen; Jin, Chunlin
Summary China is facing the great challenge of treating the world's largest rare disease population, an estimated 16 million patients with rare diseases. One effort offering promise has been a pilot national project that was launched in 2013 and that focused on 20 representative rare diseases. Another government-supported special research program on rare diseases – the “Rare Diseases Clinical Cohort Study” – was launched in December 2016. According to the plan for this research project, the unified National Rare Diseases Registry System of China will be established as of 2020, and a large-scale cohort study will be conducted from 2016 to 2020. The project plans to develop 109 technical standards, to establish and improve 2 national databases of rare diseases – a multi-center clinical database and a biological sample library, and to conduct studies on more than 50,000 registered cases of 50 different rare diseases. More importantly, this study will be combined with the concept of precision medicine. Chinese population-specific basic information on rare diseases, clinical information, and genomic information will be integrated to create a comprehensive predictive model with a follow-up database system and a model to evaluate prognosis. This will provide the evidence for accurate classification, diagnosis, treatment, and estimation of prognosis for rare diseases in China. Numerous challenges including data standardization, protecting patient privacy, big data processing, and interpretation of genetic information still need to be overcome, but research prospects offer great promise.
... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Rare Disease Patient Advocacy... Disease Patient Advocacy Day. This meeting is intended to enhance the awareness of the rare disease..., and devices) intended for the diagnosis, prevention, and/or treatment of rare diseases or...
Jeong Woo Lim; Kyung-Jo Kim; Byong Duk Ye; Jeong-Sik Byeon; Seung-Jae Myung; Suk-Kyun Yang; Jin Ho Kim
The presence of hepatic portal venous gas (HPVG) is associated with numerous diseases, and has been regarded as a serious, even catastrophic condition. However,anecdotal reports mention that some patients with inflammatory bowel disease (IBD), who developed HPVG after diagnostic examinations of the colon, were successfully managed with antibiotic therapy and have followed benign courses. In contrast, among IBD patients, the development of HPVG is rarely caused by enterovenous fistula. We describe a 32-year-old man with Crohn’s ileocolitis who presented with hypotension and fever associated with HPVG, as well as superior mesenteric vein thrombosis, possibly caused by enterovenous fistula, who was successfully managed by surgery. We also review the literature concerning portal venous gas associated with Crohn’s disease.
Full Text Available ar old female presented with complaints of asymptomatic , raised skin lesion over left leg for the past two years , which on local examination revealed a single , localized , well defined , rounded plaque of 4 cm . Clinically Bowen’s disease was not suspected because of its rarity and also occurred in the unusual site . Biopsy was taken and sent for histo - pathological examination . In histo - pathological examination Bowen’s disease was diagnosed . This case is highlighted to show the pathologist’s help in making a proper diagnosis when atypical skin lesions are seen at unusual sites . INTRODUCTION : Most of the overt malignant conditions actually originate as microscopic lesions , which are designated as in - situ carcinomas . These in - situ carcinomas are typically notic ed as intra - epithelial lesions , most often seen in squamous cell epithelial lined tissue eg . oral mucosa , genitals , cervix and skin . In skin , the intra - epithelial carcinoma - in situ lesions may be Bowen’s disease , Bowenoid papulosis or Erythroplasia of Queyrat . In the same way gastrointestinal and urinary system also can show in - situ malignancies . Bowen’s disease was first described by an American dermatologist John T Bowen in the year 1912 . It is most commonly reported in sun exposed sites . It rarely oc curs in patients with darkly pigmented skin . Bowen’s disease is observed in skin and external genitals and is sometimes associated with arsenic poisoning and visceral carcinomas . Bowen’s disease is a rare , persistent , progressive , intra - epithelial carcinom a , 8% of which will develop into an invasive squamous cell carcinoma . Treat
Chaudet, Arnaud; Goujon, Jean-Michel; Ghazali, Aiham Daniel
Horton's disease is a systemic inflammatory vasculitis, usually found in persons over 50years old. It affects medium and large-sized arteries stemming from the external carotid, especially the superficial temporal arteries. It can affect extracranial large vessels but only rarely the aorta. Diagnosis of aortitis is difficult and its incidence is probably underestimated. A 68-year-old Caucasian woman consulted in an emergency department for febrile abdominal pain with inflammatory syndrome. Abdomen was soft with right-side flank sensitivity. A contrast-enhanced CT scan showed aortitis from the descending aorta to the iliac arteries without complication. Because of age, clinical presentation and aortitis, Horton disease was suspected. The temporal artery biopsy showed a histological aspect of degenerative endarteritis with intimal thickening and luminal stenosis. High-dose corticosteroid therapy was introduced which improved clinical conditions and resulted in the amendment of the pain. In the present case, this patient had Horton's disease, based on 3 criteria of The American College of Rheumatology (age, temporal artery abnormalities and inflammatory syndrome) associated with aortitis. However, aortitis is a rare complication of Horton disease and is a major cause of mortality inasmuch as it can be complicated by aneurysm and dissection. It is unusual to diagnose Horton's disease from aortitis symptoms without complications. The aorta represents the most severe localization of Horton's disease. It should not be ignored in etiological hypotheses regarding febrile abdominal pain in the elderly. Corticosteroids should be started rapidly at high doses and temporal artery biopsy should be planned. Copyright © 2017. Published by Elsevier Inc.
Eva C Schulte
Full Text Available Approximately 20% of individuals with Parkinson's disease (PD report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset familial PD followed by frequency assessment in 975 PD cases and 1014 ethnically-matched controls and linkage analysis to identify potentially causal variants. Based on the predicted penetrance and the frequencies, a variant in PLXNA4 proved to be the best candidate and PLXNA4 was screened for additional variants in 862 PD cases and 940 controls, revealing an excess of rare non-synonymous coding variants in PLXNA4 in individuals with PD. Although we cannot conclude that the variant in PLXNA4 is indeed the causative variant, these findings are interesting in the light of a surfacing role of axonal guidance mechanisms in neurodegenerative disorders but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance.
Hyry, Hanna I; Cox, Timothy M; Roos, Jonathan C P
The UK's planned exit from the EU will leave its national health sector in a very dangerous position. It will also have profound consequences for domestic UK law. The impact may be particularly drastic for patients for whom EU law protects the right to treatment. At a particular risk are patients with rare, 'orphan', diseases whose treatments are uniquely enabled at the EU level. We examine the potential effects of Brexit on the orphan sector and identify an opportunity to solve long-standing and intensifying difficulties, especially the pricing of orphan drugs.
de Brito, Fernanda Freitas; Martelli, Antonio Carlos Ceribelli; Cavalcante, Maria Lopes Lamenha Lins; Pinto, Ana Cecília Versiani Duarte; Itimura, Gabriela; Soares, Cleverson Teixeira
Eosinophilic pustular folliculitis (EPF) or Ofuji disease is a rare dermatosis, prone to recurrence and chronicity. The peak incidence occurs in the third decade of life and its exact etiology remains unknown. Evidence suggests that the expression of adhesion molecules and the production of cytokines activate the follicular unit, but the stimulus that triggers these changes remains unclear. The three clinical variants reported in the literature include classic EPF, immunosuppression-associated EPF, and infancy-associated EPF. We report a case of eosinophilic pustular folliculitis with peculiar epidemiological characteristics, which represents a challenging therapeutic scenario. PMID:27828641
... who have a rare and potentially dangerous disease, Ehlers-Danlos syndrome. Photo Courtesy of: Patricia Weltin That has ... daughters with a rare and potentially dangerous disease, Ehlers-Danlos syndrome (EDS), a connective tissue disorder causing joint ...
Lam, Alan Cheuk Si; Lau, Vince Wing Hang [Queen Mary Hospital, Department of Radiology, Hong Kong (China); Au Yeung, Rex Kwok Him [University of Hong Kong, Department of Pathology, Li Ka Shing Faculty of Medicine, Hong Kong (China)
Kimura's disease is a rare chronic inflammatory disorder predominantly affecting young Asian male patients, occurring mainly in the head and neck regions. Kimura's disease of the upper extremity is extremely rare, and previous case reports in the literature show similar imaging characteristics with consistent location at the medial epitrochlear region, predominantly with unilateral involvement. We present the first reported case of Kimura's disease affecting the anterolateral aspect of the upper arm, sparing the medial epitrochlear region, illustrating that with typical MR appearance and serology, the involvement of this rare disease in an atypical location still warrants consideration of this diagnosis. There was also bilateral asymmetrical involvement in our patient, suggesting the possibility of a propensity for Kimura's disease affecting the upper extremities to have bilateral involvement, which may necessitate imaging of the clinically asymptomatic contralateral limb in these patients for early lesion identification and treatment. (orig.)
The spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases characterised by progressive lack of motor coordination leading to major disability. SCAs show high clinical, genetic, molecular and epidemiological variability. In the last one decade, the intensive scientific research devoted to the SCAs is resulting in clear advances and a better understanding on the genetic and nongenetic factors contributing to their pathogenesis which are facilitating the diagnosis, prognosis and development of new therapies. The scope of this chapter is to provide an updated information on Machado-Joseph disease (MJD), the most frequent SCA subtype worldwide and other rare spinocerebellar ataxias including dentatorubral-pallidoluysian atrophy (DRPLA), the X-linked fragile X tremor and ataxia syndrome (FXTAS) and the nonprogressive episodic forms of inherited ataxias (EAs). Furthermore, the different therapeutic strategies that are currently being investigated to treat the ataxia and non-ataxia symptoms in SCAs are also described.
Of the nearly 7,000 rare diseases identified by the National Institutes of Health (NIH), only a few hundred currently have treatments. The development of therapies for rare diseases is often hampered by the special challenges of conducting the needed studies for rare disease drugs and medical devices, such as small numbers of patients and the fact…
Full Text Available Background: The transmural condition of Crohn's disease predisposes to fistulae or abscesses. The internal fistula incidence is about 15%. Among them, enteroovarian fistula is rarely described on the literature. Herein, the authors present three cases of enteroovarian fistulas. Case reports: Two women are diagnosed with ileal Crohn's disease that presented a pelvic abscess diagnosed by ultrasound and CT. On surgery, an inflammatory mass involving the ileum and the ovary was found. The third woman was operated because of a tuboovarian abscess and was diagnosed with ileal Crohn's disease afterwards. In the three cases, the histopathological analysis of the ovary showed granulomas with abscess compatible with Crohn's disease. In one of the cases, multinucleated giant cells were found in the foreign body reaction to vegetable matter. A right ileocolectomy and an adnexectomy were performed in all three cases. No further involvement of the contralateral ovary or other gynaecological complications was observed. Discussion: The treatment of Crohn's disease complications should be individualized. In the case of ovarian involvement, surgical treatment should include adnexectomy.
Cristiane Rúbia Ferreira
Full Text Available Acute erythroid leukemia (AEL is a rare subtype of acute myeloid leukemia(AML, characterized by predominant erythroid proliferation. The 2008 WorldHealth Organization (WHO classification of AML defined two AEL subtypes:erythroleukaemia (EL, in which erythroid precursors account for 50% or moreof all nucleated bone marrow cells and myeloblasts account for 20% or more ofthe nonerythroid cell population; and pure erythroid leukemia (PEL, in whicherythroid precursors account for 80% or more of all nucleated bone marrowcells. We report the case of an elderly female patient with wasting syndromeand pancytopenia without evidence of blasts in peripheral blood. A diagnosisof PEL was established on the basis of bone marrow biopsy findings. Thepatient died on postadmission day 20, and an autopsy was performed. Wereclassified the disease as EL on the basis of the autopsy findings, whichincluded myeloblasts accounting for more than 20% of the nonerythroid cellsin the bone marrow, as well as leukemic infiltration and myeloid metaplasia insolid organs, such as the liver, spleen, kidneys, adrenal glands, and abdominallymph nodes. A rare disease, AEL accounts for less than 5% of all AMLs and ispractically a diagnosis of exclusion. Autopsy reports of AEL are extremely rarein the literature. We demonstrate that in the case reported here, leukemia cellstended to infiltrate solid organs with myeloid metaplasia. Our findings alsoshow that a larger neoplastic bone marrow sample is crucial to the correctdiagnosis of EL, which is based on morphological and quantitative criteria.
Trujillano, Daniel; Oprea, Gabriela-Elena; Schmitz, Yvonne; Bertoli-Avella, Aida M; Abou Jamra, Rami; Rolfs, Arndt
The ability to discover genetic variants in a patient runs far ahead of the ability to interpret them. Databases with accurate descriptions of the causal relationship between the variants and the phenotype are valuable since these are critical tools in clinical genetic diagnostics. Here, we introduce a comprehensive and global genotype-phenotype database focusing on rare diseases. This database (CentoMD (®)) is a browser-based tool that enables access to a comprehensive, independently curated system utilizing stringent high-quality criteria and a quickly growing repository of genetic and human phenotype ontology (HPO)-based clinical information. Its main goals are to aid the evaluation of genetic variants, to enhance the validity of the genetic analytical workflow, to increase the quality of genetic diagnoses, and to improve evaluation of treatment options for patients with hereditary diseases. The database software correlates clinical information from consented patients and probands of different geographical backgrounds with a large dataset of genetic variants and, when available, biomarker information. An automated follow-up tool is incorporated that informs all users whenever a variant classification has changed. These unique features fully embedded in a CLIA/CAP-accredited quality management system allow appropriate data quality and enhanced patient safety. More than 100,000 genetically screened individuals are documented in the database, resulting in more than 470 million variant detections. Approximately, 57% of the clinically relevant and uncertain variants in the database are novel. Notably, 3% of the genetic variants identified and previously reported in the literature as being associated with a particular rare disease were reclassified, based on internal evidence, as clinically irrelevant. The database offers a comprehensive summary of the clinical validity and causality of detected gene variants with their associated phenotypes, and is a valuable tool
Socha, Piotr; Vajro, Pietro; Lefeber, Dirk; Adamowicz, Maciej; Tanner, Stuart
Pediatric hepatology appears to be a very specific field of paediatrics which deals mainly with rare diseases although clinical features can be commonly found - like increased activity of transaminases. Some of these rare diseases like Wilson disease are commonly looked for and recently Wilsonian like phenotypes have been described which additionally presented with abnormal glycosylation of the plasma protein transferrin. In a subgroup of those patients with specific additional clinical symptoms (cleft uvula, low blood sugar, rhabdomyolysis and dilated cardiomyopathy) phosphoglucomutase 1 deficiency was identified. We recommend screening for abnormal glycosylation of the plasma protein transferrin in children with unexplained liver injury.
Full Text Available El concepto de Enfermedades Raras es relativamente nuevo. Suponen aquellos procesos "…que pueden ser mortales o provocar un debilitamiento crónico del paciente y que, debido a su escasa prevalencia, requieren esfuerzos combinados para tratarlas. A título indicativo, se considera una prevalencia escasa cuando es inferior a 5 casos por 10.000 personas en la Comunidad". La existencia de estas enfermedades está vinculada estrechamente con los medicamentos huérfanos, incluyendo como tales a todo fármaco, prótesis, agente biológico o preparación dietética destinado al tratamiento de una Enfermedad Rara. A este espectro hay que añadir dos factores más: 1. Los médicos de Atención Primaria no se sienten muy motivados en su conocimiento y 2. Necesitan una atención sociosanitaria compleja y habitualmente más onerosa que las enfermedades crónicas. Por todo lo expuesto las Enfermedades Raras se presentan como un universo que requiere un nuevo enfoque sociosanitario por parte de los sistemas de salud.The concept of Rare Diseases is relatively new. They are those processes "…that can be mortal or to cause a chronic weakening of the patient and who, due to its little prevalence, require combined efforts to treat them. For indicative purposes, a little prevalence is considered when is lesser than 5 cases per 10,000 people in the Community". The existence of these diseases is closely tied with orphan drugs, meaning all drugs, prosthesis, biological agents or dietetic preparations destined to the treatment of a Rare Disease. Besides, it is necessary to add two factors more: 1. The Primary Attention physicians do not feel very motivated in their knowledge and 2. These diseases need a complex sociosanitary attention, habitually more expensive than chronic diseases. By all exposed the Rare Diseases appear like a universe that requires a new sociosanitary approach from the health system.
Full Text Available The most common organ involved in hydatid disease is the liver, followed by the lungs. Hydatid disease of spleen is a rare clinical condition, as even in the endemic region the frequency is reported to be 0.5 – 4% of abdominal hydatid diseases. Most commonly splenic involvement is secondary i.e., along with other organs. Primary hydatid diseases in s pleen is rare, here we are reporting a rare case of primary splenic hydatid disease
The second workshop on "Research on Economy And Social Exclusion (REASE)" was held in the University of Tokyo on January 26, 2013. Focusing on rare diseases and disorders in China, three speakers from China introduced the current status of rare diseases and the challenge of support organizations for patients with rare disease and disorders in China, and especially pointed out some important issues associated with rare diseases and disorders in China. From the viewpoint of economics, this paper discusses some of the important issues of rare diseases and disorders in China raised in this workshop, especially from the aspects of economy of scale and orphan drugs, and the emergence of stigma from discrimination. It was shown that international coordination and cooperation are called for in order to give a proper incentive to the drug industries to create new drugs for rare diseases, and suggested that an important step toward inclusion is to reduce stigma by making rare diseases visible as much as possible.
Full Text Available Context: Retroperitoneal fibrosis is a rare but severe disease. The diagnosis is usually late when a patient is evaluated for renal insufficiency. Untreated cases may develop serious complications or advance to end-stage renal disease. Case Report: We report a 66-year-old man who presented with worsening kidney function. He was successfully given the diagnosis of idiopathic retroperitoneal fibrosis. Prednisone (1 mg/kg per day was initiated. The patient′s symptoms continued to improve at 1 month with stable kidney function. Conclusion: Clinicians should have high index of suspicion for retroperitoneal fibrosis when patients present with an elevated erythrocyte sedimentation rate (ESR or C-reactive protein (CRP and renal insufficiency from obstructive uropathy. The diagnosis of retroperitoneal fibrosis is primarily made from imaging by computed tomography (CT scan. Biopsy should be performed in patients who do not have typical findings on CT scan and to exclude the possibility of immunoglobulin G4 (IgG4-related disease.
Full Text Available Cryptogenic Multifocal Ulcerous Stenosing Enteritis (CMUSE is a rare idiopathic disease of the small bowel. Its origin and pathophysiology has not been well described. Clinicopathologic features include unexplained ileal strictures with supercial ulceration. We present a case of a 31-year-old HIV positive lady who was admitted with complaints of recurrent abdominal pain and constipation. Laboratory investigations revealed iron deciency anemia. Ultrasonography of the abdomen showed dilated bowel loops and a subsequent barium follow through showed ve strictures in the ileum. Segmental small bowel resection with end-to-end anastomosis was performed. Grossly ileum showed ve ileal strictures. The diagnosis of CMUSE was made on histopathology after ruling out other causes of strictures. The present case highlights the importance of considering CMUSE in patients with chronic or recurrent episodes of intestinal obstruction with multiple small intestinal ulcers and strictures after other common causes have been ruled out.
Zhao, Heng; Cui, Yazhou; Zhou, Xiaoyan; Pang, Jingxiang; Zhang, Xiumei; Xu, Shuangqing; Han, Jinxiang
As the world's most populous country, China has the world's largest number of rare disease groups in terms of prevalence. However, the country has no system of registering cases of most rare diseases, so there is very little documented information on the epidemiology of those diseases. The purpose of this study was to study the state of rare disease research and survey doctors in Shandong Province regarding their level of awareness of rare diseases. Types of rare diseases and numbers of cases were tallied and their geographical distribution over the decades was analyzed. Eight hundred and twenty-four doctors in tertiary hospitals and maternity and child care hospitals were surveyed by questionnaire. Data were descriptively analyzed and a map of disease distribution was created. Articles about rare diseases were retrieved from the Chinese Biomedical Literature Database to provide pertinent data. This study yielded 5,749 cases of 323 different types of rare diseases. The survey found that doctors lack awareness of research on rare diseases. An authoritative and information-rich platform for rare disease research is urgently needed. Key steps are to study epidemiological and statistical techniques and then obtain available data to provide a basis for the definition and regulation of rare diseases in China.
Swinney, D C
Only 10-15 first-in-class new medicines are approved each year by the global pharmaceutical industry for all diseases, of which less than a third is for rare (orphan) diseases. The drug discovery processes to identify rare and common diseases are similar, suggesting it will be impossible to discover new drugs for even a small fraction of the rare diseases using the current paradigm. Different approaches are required to address this large unmet medical need.
Gagne, Joshua J; Thompson, Lauren; O'Keefe, Kelly; Kesselheim, Aaron S
To examine methods for generating evidence on health outcomes in patients with rare diseases. Methodological review of existing literature. PubMed, Embase, and Academic Search Premier searched for articles describing innovative approaches to randomized trial design and analysis methods and methods for conducting observational research in patients with rare diseases. We assessed information related to the proposed methods, the specific rare disease being studied, and outcomes from the application of the methods. We summarize methods with respect to their advantages in studying health outcomes in rare diseases and provide examples of their application. We identified 46 articles that proposed or described methods for studying patient health outcomes in rare diseases. Articles covered a wide range of rare diseases and most (72%) were published in 2008 or later. We identified 16 research strategies for studying rare disease. Innovative clinical trial methods minimize sample size requirements (n=4) and maximize the proportion of patients who receive active treatment (n=2), strategies crucial to studying small populations of patients with limited treatment choices. No studies describing unique methods for conducting observational studies in patients with rare diseases were identified. Though numerous studies apply unique clinical trial designs and considerations to assess patient health outcomes in rare diseases, less attention has been paid to innovative methods for studying rare diseases using observational data. © Gagne et al 2014.
Chen, Kai; Yao, Lan; Liu, Zhiyong
Rare diseases are rarely conditions that are often debilitating and even life-threatening, which was identified by the World Health Organization (WHO) with a prevalence of 0.65-1‰. 5,000-7,000 rare diseases are thought to exist, which account for around 10% of diseases for individuals worldwide. It is estimated that over 10 million people were patients with rare disease in China. During the past years, public awareness of rare diseases has in fact heightened with the launching of campaigns by patients' organizations and spontaneous efforts by members of the public, not only in developed countries and regions including United States of America (USA), the European Union (EU), and in Japan, but also in China. However, the features of missed or delayed diagnosis, shortage of effective drugs, and the high cost of currently available drugs for rare diseases make it an important public health issue and a challenge to medical care worldwide. To combat rare disease, the government should assume the responsibility of taking on the important task of promoting the sustained development of a system of medical care for and research into rare diseases. Government-funded special biomedical research programs in the USA, EU, and Japan may serve as a reference for China coping with rare diseases. The government-funded special biomedical research programs consisting of leading clinicians and researchers to enhance basic and applied research on rare diseases were expected to be launched in China.
Segal, Brahm H; Veys, Paul; Malech, Harry; Cowan, Morton J
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency with X-linked or autosomal recessive inheritance involving defects in genes encoding phox proteins, which are the subunits of the phagocyte NADPH oxidase. This results in failure to produce superoxide anion and downstream antimicrobial oxidant metabolites and to activate antimicrobial proteases. Affected patients are susceptible to severe, life-threatening bacterial and fungal infections and excessive inflammation characterized by granulomatous enteritis resembling Crohn's disease and genitourinary obstruction. Early diagnosis of CGD and rapid treatment of infections are critical. Prophylaxis with antibacterial and mold-active antifungal agents and the administration of interferon-γ has significantly improved the natural history of CGD. Currently, the only cure is allogeneic hematopoietic cell transplant (HCT), although there remains controversy as to which patients with CGD should get a transplant. Allele-based HLA typing of alternative donors, improved supportive care measures, and use of reduced toxicity conditioning have resulted in event-free survival (EFS) of at least 80% even with an unrelated donor and even better when the patient has no active infections/inflammation. Gene correction of CGD would eliminate the risks of graft-versus-host disease (GVHD) and the immunoablative chemotherapy required for allogeneic HCT. Based on gene therapy trials in patients with SCID-X1, ADA-SCID, and the early experience with CGD, it is clear that at least some degree of myeloablation will be necessary for CGD as there is no inherent selective growth advantage for gene-corrected cells. Current efforts for gene therapy focus on use of lentivector constructs, which are thought to be safer from the standpoint of insertional mutagenesis and more efficient in transducing hematopoietic stem cells (HSCs).
Colledge Vicki L
Full Text Available Abstract Resources for rare diseases are lacking. Patients do not have the information and support that they need, and researchers struggle to make progress due to a shortage of skills and collaborations within the field. One way to overcome these hurdles is to host annual Symposia, focused on a specific rare disease. Here, we use the example of Birt-Hogg-Dubé Symposia to discuss the practical issues of such meetings, including the importance of timing and the choice of invited speakers. We highlight the ways in which rare disease symposia can create a single community, removing barriers between patients, clinicians and researchers.
Sensibilidad y especificidad de la prueba de esfuerzo y el estudio de perfusión miocárdica con SESTAMIBI para detección de enfermedad arterial coronaria, en el Hospital San Juan de Dios Sensitivity and Specificity of Treadmill Test and Myocardial Perfusion Imaging with SESTAMIBI in the detection of Coronary Artery Disease at the Hospital San Juan de Dios
Juan Pablo Solís-Barquero
Full Text Available Objetivo: La coronariopatía arterio esclerótica continúa siendo la principal causa de mortalidad mundial y Costa Rica no escapa a esta realidad. La prueba de esfuerzo, la imagen de perfusión con SESTAMIBI y la angiografía coronaria son métodos que permiten detectar esta entidad. El país no cuenta con datos sobre la información que proporcionan estas pruebas. El objetivo del estudio es determinar la rentabilidad diagnóstica de cada una de ellas. Métodos: Es un estudio observacional, analítico de cohorte. Se incluyeron pacientes con factores de riesgo cardiovascular, que tuvieran prueba de esfuerzo, estudio de perfusión miocárdica y angiografía coronaria realizadas en el Hospital San Juan de Dios, desde 2003 a 2007. Se calculó la sensibilidad y especificidad de estos estudios. También se llevó a cabo un análisis con una estadística descriptiva de las características de la muestra y de los diferentes factores de riesgo cardiovascular. Resultados: Se incluyeron 83 pacientes en el estudio, 75% hombres. Los principales factores de riesgo encontrados fueron dislipidemia (84% e hipertensión arterial (70%. La prueba de esfuerzo tuvo una sensibilidad del 40% y una especificidad del 57%; el estudio de perfusión miocárdica con SESTAMIBI tuvo una sensibilidad del 66% y una especificidad del 71%. La mayoría de los pacientes tuvieron afección de uno o dos vasos coronarios, con lesiones mayores al 90%, y especialmente en la arteria descendente anterior. Conclusión: Los factores de riesgo convencionales se presentaron en un alto porcentaje de la población estudiada. La prueba de esfuerzo mostró una baja sensibilidad y especificidad, sin embargo, coincide con el rango descrito en la literatura. El estudio de perfusión miocárdica con SESTAMIBI mostró un rendimiento diagnóstico significativamente superior (p =0.05.Aim: Coronary artery disease is the first cause of mortality around the world, and Costa Rica does not escape from this
Cui, Yazhou; Zhou, Xiaoyan; Han, Jinxiang
China is facing the great challenge of serving the world's largest rare disease population. It is necessary to develop a specific medical plan to increase the levels of optimal prevention, diagnosis and treatment of rare diseases under the existing clinical service structures in China. In 2013, China launched its first pilot project focused on 20 representative rare diseases. A national network including approximately 100 provincial or municipal medical centers has been established to enable collaboration on rare diseases across China. The main objectives for this project are to develop and apply medical guidelines and clinical pathways for rare diseases, to establish a rare disease patient registry and data repository system, and to promote molecular testing for rare genetic disorders. This project also emphasizes building close links among the collaborative network, clinicians on the frontlines in basic medical services institutions and rare disease patient organizations. Primarily, this project expects to develop an actionable medical services plan to increase the delivery of quality healthcare for individuals and families living with rare diseases in China within five years.
Julkowska, D; Austin, C P; Cutillo, C M; Gancberg, D; Hager, C; Halftermeyer, J; Jonker, A H; Lau, L P L; Norstedt, I; Rath, A; Schuster, R; Simelyte, E; van Weely, S
Over the last two decades, important contributions were made at national, European and international levels to foster collaboration into rare diseases research. The European Union (EU) has put much effort into funding rare diseases research, encouraging national funding organizations to collaborate together in the E-Rare program, setting up European Reference Networks for rare diseases and complex conditions, and initiating the International Rare Diseases Research Consortium (IRDiRC) together with the National Institutes of Health in the USA. Co-ordination of the activities of funding agencies, academic researchers, companies, regulatory bodies, and patient advocacy organizations and partnerships with, for example, the European Research Infrastructures maximizes the collective impact of global investments in rare diseases research. This contributes to accelerating progress, for example, in faster diagnosis through enhanced discovery of causative genes, better understanding of natural history of rare diseases through creation of common registries and databases and boosting of innovative therapeutic approaches. Several examples of funded pre-clinical and clinical gene therapy projects show that integration of multinational and multidisciplinary expertize generates new knowledge and can result in multicentre gene therapy trials. International collaboration in rare diseases research is key to improve the life of people living with a rare disease.
Full Text Available La baja talla constituye el primer motivo de consulta en endocrinología pediátrica. En un alto porcentaje su etiología es clara y obedece fundamentalmente a variantes de normalidad. Sin embargo, en aproximadamente un 20% esta baja talla es patológica y obliga a estudios exhaustivos. La asociación de enfermedades raras (ER con talla baja es altamente frecuente. En este trabajo repasamos las etiologías de la baja talla en enfermedades raras, describiendo: - las formas genéticas de la hormona de crecimiento (GH bien sean aisladas o asociadas a malformaciones de la línea media u otras. - aquellas de gran importancia por su repercusión clínica como el Síndrome de Turner, Síndrome de Noonan y el Síndrome de Willi-Prader. - Las frecuentes displasias óseas, con alteración genética en algunos casos para el gen SHOX, situado en el brazo corto del cromosoma Xp. La importancia de estos diagnósticos radica en la posibilidad de hacer un tratamiento precoz y eficaz, en algunos de ellos, con GH. En conclusión, el diagnóstico de enfermedades raras con baja talla es un reto actual y habitual en endocrinología pediátrica por los grandes avances de la genética molecular y la posibilidad de tratamiento en algunas de ellas. Implica siempre un abordaje multidisciplinario por la asociación frecuente de patología que presenta y a su vez, ofrece la posibilidad de realizar el oportuno consejo genético.Low stature is the main reason of consultation in paediatric endocrinology. In a high percentage of cases, its etiology is clear and fundamentally answers to variants of normality. However, in approximately 20% of cases low stature is pathological and requires exhaustive studies. The association of rare diseases (RD with low height is very frequent. In this article we review the etiology of low height, describing: - The genetic forms of the growth hormone (GH, whether isolated or associated with malformations of the average line or others. - Those
Desser, Arna S
Understanding doctors' preferences for prioritizing treatment of rare diseases can provide an important context for policy makers who must decide whether to exempt rare disease treatments, which are often quite expensive, from standard cost-effectiveness criteria. We surveyed a random sample of 551 Norwegian doctors in November 2011 and compared results to a similar survey of the Norwegian population. Respondents chose whether to prioritize treatment of patients with rare versus common diseases and then decided how to allocate funds between the two groups for each of two scenarios: (1) equal costs per person and (2) higher costs for the rare disease. Respondents were randomized to treatment costs for the rare disease in the second scenario that were either 8 or 25 times higher than treating the common disease. Except for different prevalence, the diseases were described identically. Doctors displayed no general preference for prioritizing treatment of rare diseases, but a large number favored the principle of reserving a small share of funds for rare disease patients. Doctors' responses differed significantly from those of the general population when the rare disease was more costly to treat. A larger share of doctors prioritized the common disease group for treatment while a smaller share expressed indifference. When dividing funds between the two patient groups, doctors allocated a smaller share of funds to the rare disease. Doctors were much less likely than the general population to divide funds equally between the groups. This study indicates that there is little support among Norwegian doctors for prioritizing the treatment of rare diseases.
Gupta, Samir; Bayoumi, Ahmed M; Faughnan, Marie E
Research in rare lung diseases faces methodologic limitations by virtue of the small number of participants available to be studied. We explored several strategies that may improve researchers' ability to identify and recruit research participants with rare lung diseases. We provide an overview of strategies based on available evidence, previously used approaches, and reasoning. First, disease detection is generally poor and may be improved through strategies targeted at primary care practitioners or directly at patients, thus increasing the pool of patients available for research studies. Next, standardization of case definitions in rare lung diseases is often lacking, hindering research recruitment efforts because of confusion over appropriate recruitment criteria. Expert consensus statements can enhance both clinical care and research recruitment by standardizing definitions. Finally, recruitment strategies using rare lung disease registries, clinical research networks, novel Internet-based direct patient recruitment approaches, and patient organizations may facilitate recruitment of patients with rare lung diseases. In summary, although several strategies for improving the identification and recruitment of research participants with rare lung diseases have been proposed, published examples are few. Objective measurement and reporting of novel recruitment methods and collaboration among researchers facing the same limitations across various rare lung diseases are required. Advancements in this area are vital to the design and performance of much-needed robust clinical studies across the spectrum of rare lung diseases.
The incidence of mental health disorders is significantly higher in individuals with a rare disease, compared to the general population. This letter considers the possible reasons for this in terms of the many ways in which a rare disease impacts on an individual's life, and how these impacts can be strongly related to factors which predispose to mental health difficulties.Furthermore, issues surrounding mental health can also play a significant role in the process of diagnosing a rare disease. The unusual nature of such diseases intrinsically predisposes an individual to obtain an inaccurate diagnosis of a psychosomatic disorder, a diagnosis which can often be further complicated by the presence of genuine psychiatric symptoms.This letter argues that these common experiences of rare disease patients have impacts upon the way in which their psychiatric care should be offered and managed, and that sensitivity and understanding surrounding these issues should be considered a necessary part of effective care for rare disease patients.
Alves, Maria M; Sribudiani, Yunia; Brouwer, Rutger W W; Amiel, Jeanne; Antiñolo, Guillermo; Borrego, Salud; Ceccherini, Isabella; Chakravarti, Aravinda; Fernández, Raquel M; Garcia-Barcelo, Maria-Mercè; Griseri, Paola; Lyonnet, Stanislas; Tam, Paul K; van Ijcken, Wilfred F J; Eggen, Bart J L; te Meerman, Gerard J; Hofstra, Robert M W
Finding genes for complex diseases has been the goal of many genetic studies. Most of these studies have been successful by searching for genes and mutations in rare familial cases, by screening candidate genes and by performing genome wide association studies. However, only a small fraction of the total genetic risk for these complex genetic diseases can be explained by the identified mutations and associated genetic loci. In this review we focus on Hirschsprung disease (HSCR) as an example of a complex genetic disorder. We describe the genes identified in this congenital malformation and postulate that both common 'low penetrant' variants in combination with rare or private 'high penetrant' variants determine the risk on HSCR, and likely, on other complex diseases. We also discuss how new technological advances can be used to gain further insights in the genetic background of complex diseases. Finally, we outline a few steps to develop functional assays in order to determine the involvement of these variants in disease development.
Silva, Igor Henrique; Cardoso, Samantha; Carvalho, Camila Nunes; Carvalho, Alessandra Albuquerque Tavares; Leão, Jair Carneiro; Gueiros, Luiz Alcino
Oral mucoceles are common lesions characterized by accumulation of mucus following rupture of a minor salivary gland duct. However, congenital mucoceles are a rare and distinctive oral condition observed in newborns. This case report details the features of a congenital labial nodule diagnosed as congenital mucocele. These lesions are rare in the oral cavity and should be diagnosed in the delivery room, but many cases are referred for further evaluation. Management is simple, and recurrence is not expected.
Newman, Samantha Kass; Jayanthan, Raj K; Mitchell, Grant W; Carreras Tartak, Jossie A; Croglio, Michael P; Suarez, Alexander; Liu, Amy Y; Razzo, Beatrice M; Oyeniran, Enny; Ruth, Jason R; Fajgenbaum, David C
Castleman disease (CD) is a rare and heterogeneous disorder characterized by lymphadenopathy that may occur in a single lymph node (unicentric) or multiple lymph nodes (multicentric), the latter typically occurring secondary to excessive proinflammatory hypercytokinemia. While a cohort of multicentric Castleman disease (MCD) cases are caused by Human Herpes Virus-8 (HHV-8), the etiology of HHV-8 negative, idiopathic MCD (iMCD), remains unknown. Breakthroughs in "omics" technologies that have facilitated the development of precision medicine hold promise for elucidating disease pathogenesis and identifying novel therapies for iMCD. However, in order to leverage precision medicine approaches in rare diseases like CD, stakeholders need to overcome several challenges. To address these challenges, the Castleman Disease Collaborative Network (CDCN) was founded in 2012. In the past 3 years, the CDCN has worked to transform the understanding of the pathogenesis of CD, funded and initiated genomics and proteomics research, and united international experts in a collaborative effort to accelerate progress for CD patients. The CDCN's collaborative structure leverages the tools of precision medicine and serves as a model for both scientific discovery and advancing patient care.
Full Text Available En coup de sabre (linear scleroderma of face is a rare type of morphea (localized scleroderma involving frontoparietal area of the forehead and scalp. Many triggering factors have been implicated in the development of morphea like trauma, immobilization, bacille Calmette–Guérin (BCG vaccination, injections of vitamin K, mechanical compression from clothing, etc. Linear scleroderma primarily affects the pediatric population, with 67% of patients diagnosed before 18 years of age. In this article, we describe a case of 26 year old female who presented with a three months history of brownish indurated plaque of skin on the frontal and forehead regions of the head. The patient gave a history of trauma at the same site six years back. The diagnosis of morphea was made clinically supported by histopathological features of the skin biopsy. Her neurological examination was normal. ANA was negative. Brain MRI didn’t reveal any abnormality. She was treated with topical tacrolimus 0.1% ointment. The late onset en coup de sabre is a rare presentation and hence reported.
Gorlov, I P; Gorlova, O Y; Frazier, M L; Spitz, M R; Amos, C I
The common disease/common variant hypothesis has been popular for describing the genetic architecture of common human diseases for several years. According to the originally stated hypothesis, one or a few common genetic variants with a large effect size control the risk of common diseases. A growing body of evidence, however, suggests that rare single-nucleotide polymorphisms (SNPs), i.e. those with a minor allele frequency of less than 5%, are also an important component of the genetic architecture of common human diseases. In this study, we analyzed the relevance of rare SNPs to the risk of common diseases from an evolutionary perspective and found that rare SNPs are more likely than common SNPs to be functional and tend to have a stronger effect size than do common SNPs. This observation, and the fact that most of the SNPs in the human genome are rare, suggests that rare SNPs are a crucial element of the genetic architecture of common human diseases. We propose that the next generation of genomic studies should focus on analyzing rare SNPs. Further, targeting patients with a family history of the disease, an extreme phenotype, or early disease onset may facilitate the detection of risk-associated rare SNPs.
Polenakovic, Momir; Gucev, Zoran; Tasic, Velibor
In Europe Rare Disease (RD) is the one which affects less than 1/2000, in the USA 1/1250, while in Japan RD is the one that affects fewer than 1/50,000 patients. EU estimates that 5-8000 distinct rare diseases affect 6-8% of the Population. The impact of rare diseases in the health systems is impresssive: at least 3 million patients in the UK, 4 million in Germany, and between 27 and 36 million EU citizens. There is not a precise register for rare diseases in the Republic of Macedonia. Rare diseases are becoming increasingly important as possible targets of new forms of treatment, as a valuable source of a novel insight in fundamental lows of biology, and in the specific mechanisms of many diseases. Molecular methods have created a better diagnosis and oftentimes treatment. Rare diseases pose significant problem for the patients, since their problems are often not recognized by the medical community and shunned by the health insurance. The cumulative costs of diagnosis and treatment of rare diseases is significant for any society and oftentimes not acceptable for developing countries.
Perros, Petros; Hegedüs, L; Bartalena, L.
qualify as rare. Recent published data on the incidence of GO and Graves' hyperthyroidism in Europe were used to estimate the prevalence of GO. The position statement was developed by a series of reviews of drafts and electronic discussions by members of the European Group on Graves' Orbitopathy...
Full Text Available Reticulate acropigmentation of Kitamura (RAK is a rare, autosomal dominant disorder first described in Japan characterised by a reticulate pattern of slightly atrophic, angulated, hyperpigmented macules affecting the acral areas of the body. We hereby report a case of RAK in a young Indian male with adermatoglyphia that has not been previously reported in the literature.
Summary The second workshop on “Research on Economy And Social Exclusion (REASE)” was held in the University of Tokyo on January 26, 2013. Focusing on rare diseases and disorders in China, three speakers from China introduced the current status of rare diseases and the challenge of support organizations for patients with rare disease and disorders in China, and especially pointed out some important issues associated with rare diseases and disorders in China. From the viewpoint of economics, this paper discusses some of the important issues of rare diseases and disorders in China raised in this workshop, especially from the aspects of economy of scale and orphan drugs, and the emergence of stigma from discrimination. It was shown that international coordination and cooperation are called for in order to give a proper incentive to the drug industries to create new drugs for rare diseases, and suggested that an important step toward inclusion is to reduce stigma by making rare diseases visible as much as possible. PMID:25343098
Mihalek, Andrew D; Haney, Carissa; Merino, Maria; Roy-Chowdhuri, Sinchita; Moss, Joel; Olivier, Kenneth N
Amyloid primarily affecting the lungs is a seldom seen clinical entity. This case discusses the work-up of a patient presenting with exercise-induced haemoptysis and diffuse cystic lung disease on radiographic imaging. The common clinical and radiographic findings of diffuse cystic lung diseases as well as a brief overview of pulmonary amyloid are presented. 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/
Shaik Afshan Jabeen
Full Text Available Leigh syndrome (LS is a heterogeneous familial or sporadic neurodegenerative disorder. It is typically seen in infancy or childhood, although rare cases of adult onset have been described. The authors describe a 37-year-old woman who presented with protracted gastrointestinal symptoms followed by acute brain stem syndrome with severe metabolic acidosis and who subsequently showed dramatic clinical and neuroradiological improvement.
Lawtongkum, Weerasak; Thisyakorn, Usa
The prevalence of Listeria monocytogenes infection has been characterized as rare in Thailand. Within one month, 3 cases of listeriosis were seen at Vachira Phuket Hospital in Phuket, Thailand. Two cases were neonates with septicemia, of which one made an uneventful recovery and the other expired. The third case was an eleven-year-old boy with meningitis who also succumbed to his illness. All isolated L. monocytogenes were sensitive to ampicillin. An outbreak investigation revealed no L. monocytogenes contamination in tested food sources in Phuket.
De Rose, Aldo F; Mantica, Guglielmo; Piol, Nataniele; Toncini, Carlo; Spina, Bruno; Terrone, Carlo
Leiomyomas are rare benign tumors that can occur in the male urinary tract. We present a unique case of leiomyoma of the vas deferens. We present the clinical case of a 69-year-old patient with a suspected bulk close to the right epididymis, which turned out to be a leiomyoma of the vas deferens. To our knowledge, it is the fourth case in literature. A proper identification and the knowledge of this pathology, even if it is a very unusual event, is necessary to avoid a surgical over treatment and preserve the testicle, by removing only the tumor.
Full Text Available Marchiafava- Bignami disease is the symmetrical demyelination of the corpus callosum, mostly observed in people with chronic alcoholism & sometimes in people with chronic nutritional deficiency. We have been reported such case of a male patient who had history of chronic alcoholism, different clinical presentation and MRI findings consistent with the diagnosis of Marchiafava- Bignami disease.
G.W., Van Broeckhoven C, Vance, J.M.: “Parkinson Disease Variant Database ”. MDS 19th International Congress of Parkinson’s Disease and Movement...abstracts submitted to ( international ) meetings and announcements of seminars including presentation of the database . Page 9 ABSTRACT NUYTEMANS UDALL...
Sanjay N. Agrawal
Full Text Available A female patient presented with progressive weakness, asthenia and generalized hyperpigmentation. The characteristic hyperpimentation pointed towards possibility of Addison’s disease which was proved by markedly decreased plasma cortisol levels, hyponatremia and hyperkalemia. This could be one of the very few cases of Addison’s Disease reported.
Full Text Available Purpose. Electronic health record systems provide great opportunity to study most diseases. Objective of this study was to determine whether electronic medical records (EMR in ophthalmology contribute to management of rare eye diseases, isolated or in syndromes. Study was designed to identify and collect patients’ data with ophthalmology-specific EMR. Methods. Ophthalmology-specific EMR software (Softalmo software Corilus was used to acquire ophthalmological ocular consultation data from patients with five rare eye diseases. The rare eye diseases and data were selected and collected regarding expertise of eye center. Results. A total of 135,206 outpatient consultations were performed between 2011 and 2014 in our medical center specialized in rare eye diseases. The search software identified 29 congenital aniridia, 6 Axenfeld/Rieger syndrome, 11 BEPS, 3 Nanophthalmos, and 3 Rubinstein-Taybi syndrome. Discussion. EMR provides advantages for medical care. The use of ophthalmology-specific EMR is reliable and can contribute to a comprehensive ocular visual phenotype useful for clinical research. Conclusion. Routinely EMR acquired with specific software dedicated to ophthalmology provides sufficient detail for rare diseases. These software-collected data appear useful for creating patient cohorts and recording ocular examination, avoiding the time-consuming analysis of paper records and investigation, in a University Hospital linked to a National Reference Rare Center Disease.
Conclusion: This is a rare case of spinal Rosai–Dorfman Disease with epidural and intradural components causing cord compression. To our knowledge, this represents the first case of combined epidural and intradural extramedullary lesions in the literature.
Brooks, Kristina; Caruthers, Regine L; Schumacher, Kurt R; Stringer, Kathleen A
Pediatric pharmacotherapy is often challenging due to the paucity of available clinical data on the safety and efficacy of drugs that are commonly used in children. This quandary is even more prevalent in children with rare diseases. Although extrapolations for dosing and administration are often made from available adult data with similar disease states, this translation becomes even more problematic in rare pediatric diseases. Understanding of rare disease pathophysiology is typically poor, and few, if any, effective therapies have been studied and identified. One condition that illustrates these issues is plastic bronchitis, a rare, most often pediatric disease that is characterized by the production of obstructive bronchial airway casts. This illness primarily occurs in children with congenital heart disease, often after palliative surgery. Plastic bronchitis is a highly clinically relevant and therapeutically challenging problem with a high mortality rate, and, a generally accepted effective pharmacotherapy regimen has yet to be identified. Furthermore, the disease is ill defined, which makes timely identification and treatment of children with plastic bronchitis difficult. The pharmacotherapies currently used to manage this disease are largely anecdotal and vary between the use of macrolide antibiotics, mucolytics, bronchodilators, and inhaled fibrinolytics in a myriad of combinations. The purpose of this review is 2-fold: first, to highlight the dilemma of treating plastic bronchitis, and second, to bring attention to the continuing need for studies of drug therapies used in children so safe and effective drug regimens can be established, particularly for rare diseases. © 2013 Pharmacotherapy Publications, Inc.
Pariser, Anne R; Gahl, William A
Rare diseases play a leading role in innovation and the advancement of medical and pharmaceutical science. Most rare diseases are genetic disorders or atypical manifestations of infectious, immunologic, or oncologic diseases; they all provide opportunities to study extremes of human pathology and provide insight into both normal and aberrant physiology. Recently, drug development has become increasingly focused on classifying diseases largely on genetic grounds; this has allowed the identification of molecularly defined targets and the development of targeted therapies. Clinical trials are now focusing on progressively smaller subgroups within both common and rare disease populations, often based on genetic tests or biomarkers. Drug developers, researchers, and regulatory agencies face a variety of challenges throughout the life cycle of drug research and development for rare diseases. These include the small numbers of patients available for study, lack of knowledge of the disease's natural history, incomplete understanding of the basic mechanisms causing the disorder, and variability in disease severity, expression, and course. Traditional approaches to rare disease clinical research have not kept pace with advances in basic science, and increased attention to translational science is needed to address these challenges, especially diagnostic testing, registries, and novel trial designs.
Osmanagic, Azra; Emamifar, Amir; Christian Bang, Jacob;
BACKGROUND Pott's disease (PD) or spinal tuberculosis is a rare condition which accounts for less than 1% of total tuberculosis (TB) cases. The incidence of PD has recently increased in Europe and the United States, mainly due to immigration; however, it is still a rare diagnosis in Scandinavian...
Gül, Fatih; Berçin, Sami; Müderris, Togay; Yalçıner, Gökhan; Ünal, Özkan; Kırış, Muzaffer
A 38-year-old female patient experienced a sudden onset of unilateral sensorineural hearing loss due to Moyamoya disease. A detailed summary of audiological and neurological findings indicated that the sudden hearing loss might be due to Moyamoya disease resulting in occlusion of posterior and middle cerebral arteries. Intravenous prednisolone and trimetazidine dihydrochloride may improve hearing thresholds and speech understanding. To our knowledge, this is the first article in the literature reporting a case of sudden hearing loss as the first manifestation of Moyamoya disease in a young adult.
Kadabur Nagendrappa Lokesh
Full Text Available Adult peripheral neuroblastoma represents less than 1% of all malignant primary tumors of peripheral nerves. We report a young adult who presented with swelling over the left wrist with left epitrochlear and axillary lymph nodes. Incision biopsy of the swelling was suggestive of malignant small round cell tumor. On immunohistochemistry, cells were positive for synaptophysin, chromogranin and nonspecific enolase and negative for leucocyte common antigen, cytokeratin, CD99 and myogenin. Urinary vanillyl mandelic acid and homovanillic acid levels were elevated. The patient received 8 cycles of chemotherapy (OJEC. Reassessment positron emission tomography-computed tomography scan showed a complete metabolic response at the primary site and partial response at left axillary lymph nodes. The patient underwent axillary lymph node clearance followed by radiotherapy to the tumor bed and lymph node regions. The patient could not afford autologous haematopoetic stem cell transplant and was started on isotretinoin maintenance. He is on follow-up for 12 months and disease free.
Health outcomes for rare diseases can be greatly affected by timely diagnosis.This paper presents a narrative review of current literature on rare diseases, with a focuson Pulmonary Arterial Hypertension (PAH), to identify needs for early diagnosisinitiatives. The review assessed: what needs to be done, what is currently being done,and what are the approaches or change theories that underlie these initiatives.Literature from online key-word searches included academic articles pertaining todia...
Lynch, Sally Ann; Borg, Isabella
The origins of clinical genetics services vary throughout Europe with some emerging from paediatric medicine and others from an academic laboratory setting. In 2011, the cross-border patients' rights directive recommended the creation of European Research Networks (ERNs) to improve patient care throughout EU. In 2013, the EU recommendation on the care for rare diseases came into place. The process of designating EU centres of expertise in rare diseases is being implemented to allow centres to enter ERNs. Hence, this is an opportune time to reflect on the current status of genetic services and research funding throughout Europe as 80 % of rare diseases have a genetic origin. Our aims were to determine (a) whether EU countries are prepared in terms of appropriate clinical genetic staffing to fulfil the European Union Committee of Experts on Rare Diseases (EUCERD) criteria that will allow national centres to be designated as centres of expertise, (b) which EU countries are successful in grant submissions to EU rare disease research funding and (c) country of origin of researchers from the EU presenting their research work as a spoken presentation at the European Society of Human Genetics annual conference. Our results show there is wide disparity of staffing levels per head of population in clinical genetics units throughout Europe. EU rare disease research funding is not being distributed equitably and the opportunity to present research is skewed with many countries not achieving spoken presentations despite abstract submissions. Inequity in the care of patients with rare diseases exists in Europe. Many countries will struggle to designate centres of expertise as their staffing mix and levels will not meet the EUCERD criteria which may prevent them from entering ERNs. The establishment of a small number of centres of expertise centrally, which is welcome, should not occur at the expense of an overall improvement in EU rare disease patient care. Caution should be
Richesson, Rachel; Sutphen, Rebecca; Shereff, Denise; Krischer, Jeff
The Rare Diseases Clinical Research Network (RDCRN) Contact Registry has grown in size and scope since it was first reported in this journal in 2007. In this paper, we reflect on our seven years’ experience developing and expanding the RDCRN Contact Registry to include many more rare diseases. We present the functional and data requirements that motivated this registry, and the new features and policies that have been developed since. Given the high costs and long-term commitme...
Full Text Available Background/Aim. Rare diseases are chronic, degenerative and may lead to permanent disability. We aimed to assess knowledge and attitudes of the 3rd and 6th year medical students towards the treatment of rare diseases in Serbia. Methods. In this cross-sectional study, two samples of students were questioned for a survey: 350/446 (78.48% students of the 3rd year, and 242/517 (46.81% students of the 6th year. Results. Sixth year students estimated that they were more informed on the issue analyzed than the 3rd year students (median value of 4 and 3, interquartile range of 3-5, and 1-4, respectively; p < 0.05. However, a significant percentage of participants estimated incorrectly the prevalence of rare diseases according to the European Union standards (3rd year - 42.68%, 6th year - 49.55%. Core curriculum subjects were the main source of information on rare diseases (3rd year - 63.14%; 6th year - 92.14%. Our participants agreed that the most important problems are the following: high drug prices, difficult access to drugs and lack of public information. Students found, without any differences, that community access to effective drugs for rare disease should be improved (median value - 10, interquartile range 8-10 in both groups, p < 0.05. In order to improve pharmacotherapy of rare diseases in Serbia, the participants suggested establishment of a National Plan for Rare Diseases, approval of more appropriate drugs, simplified access to appropriate medicines, and more rapid diagnostics. Conclusion. It is necessary to improve the knowledge and attitudes of medical students towards pharmacotherapy of rare diseases. [Projekat Ministarstva nauke Republike Srbije, br. 175023
Full Text Available Gaucher´s disease consists of a genetic autosomic recesive alteration that leads to a reduction in the acid glucosil-ceramide beta-glucosidase enzyme. This enzyme brakes the glucosilceramide, a substance from which many esphingo and glucolipids are synthesized. Even though the renal compromise is not frequent in Gaucher disease, proteinuria (in nephrotic range or not and glomerulonephritis have been described in this illness.Fanconi syndrome is charaterized by a dysfunction in the proximal tubular reabsorption. Among the etiologies of Fanconi syndrome there are many metabolic diseases, but no association has been described yet in the literature between Fanconi syndrome and Gaucher disease. We present the following case report where this association was observed.
Rudolf, Volker H.W.; Antonovics, Janis
Cannibalism has been documented as a possible disease transmission route in several species, including humans. However, the dynamics resulting from this type of disease transmission are not well understood. Using a theoretical model, we explore how cannibalism (i.e. killing and consumption of dead conspecifics) and intraspecific necrophagy (i.e. consumption of dead conspecifics) affect host–pathogen dynamics. We show that group cannibalism, i.e. shared consumption of victims, is a necessary c...
Full Text Available Hydatid disease is one of the most geographically widespread zoonoses with substantial disease burden. In this report we are discussing an unusual case of intra-abdominal HD that was ongoing for 22 years despite two surgical interventions. Significant symptomatic relief was achieved within the first two months of combination therapy with albendazole and praziquantel. HD is still of public health concern in the Middle East that needs optimized care.
Almalik, Abdulrahman; Alsharidi, Aynaa; Al-Sheef, Mohammed; Enani, Mushirah
Hydatid disease is one of the most geographically widespread zoonoses with substantial disease burden. In this report we are discussing an unusual case of intra-abdominal HD that was ongoing for 22 years despite two surgical interventions. Significant symptomatic relief was achieved within the first two months of combination therapy with albendazole and praziquantel. HD is still of public health concern in the Middle East that needs optimized care. PMID:25114815
Charles R.Farber; Thomas L.Clemens
Recent improvements in the speed and accuracy of DNA sequencing, together with increasingly sophisti-cated mathematical approaches for annotating gene networks, have revolutionized the field of human genetics and made these once time consuming approaches assessable to most investigators. In the field of bone research, a particularly active area of gene discovery has occurred in patients with rare bone disorders such as osteogenesis imperfecta (OI) that are caused by mutations in single genes. In this perspective, we highlight some of these technological advances and describe how they have been used to identify the genetic determinants underlying two previously unexplained cases of OI. The widespread availability of advanced methods for DNA sequencing and bioinformatics analysis can be expected to greatly facilitate identification of novel gene networks that normally function to control bone formation and maintenance.
Full Text Available A 27-year-old African American male presented with a sudden onset of blisters. He had a past medical history of uncontrolled diabetes mellitus type I, diabetic vasculopathy, and neuropathy. The physical examination revealed nonerythematous skin denudations on both elbows and lateral aspect of arm bilaterally. Investigations which included skin biopsies confirmed the diagnosis of bullosis diabeticorum. The bullae were treated with hydrotherapy and healed with no complications in 4 weeks. We present this case to illustrate the rare occurrence of diabetic bulla in a diabetic patient especially with poor glycemic control. The case is also a reminder of the importance of diabetes screening in nondiabetic patients who are diagnosed with diabetic bulla.
Wuhl, E.; Stralen, K.J. van; Wanner, C.; Ariceta, G.; Heaf, J.G.; Bjerre, A.K.; Palsson, R.; Duneau, G.; Hoitsma, A.J.; Ravani, P.; Schaefer, F.; Jager, K.J.
BACKGROUND: In recent years, increased efforts have been undertaken to address the needs of patients with rare diseases by international initiatives and consortia devoted to rare disease research and management. However, information on the overall prevalence of rare diseases within the end-stage ren
Walter, Klaudia; Min, Josine L; Huang, Jie;
The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively......-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive...
Ekins, Sean; Wood, Jill
Starting biotech or pharmaceutical companies is traditionally thought to be based around a scientist, their technology platform or a clinical candidate spun out from another company. Between us we have taken a different approach and formed two small early stage companies after initially leveraging the perspective of a parent with a child with a life-threatening rare disease. Phoenix Nest ( http://www.phoenixnestbiotech.com/ ) was co-founded to work on treatments for Sanfilippo syndrome a devastating neurodegenerative lysosomal storage disorder. In the space of just over 3 years we have built up collaborations with leading scientists in academia and industry and been awarded multiple NIH small business grants. The second company, Collaborations Pharmaceuticals Inc. ( http://www.collaborationspharma.com/ ) was founded to address some of the other 7000 or so rare diseases as well as neglected infectious diseases. The Rare Pediatric Disease Priority Review Voucher is likely the most important incentive for companies working on rare diseases with very small populations. This may also be partially responsible for the recent acquisitions of rare disease companies with late stage candidates. Lessons learned in the process of starting our companies are that rare disease parents or patients can readily partner with a scientist and fund research through NIH grants rather than venture capital or angel investors initially. This process may be slow so patience and perseverance is key. We would encourage other pharmaceutical scientists to meet rare disease parents, patients or advocates and work with them to further the science on their diseases and create a source of future drugs.
Beaulieu, Chandree L; Majewski, Jacek; Schwartzentruber, Jeremy; Samuels, Mark E; Fernandez, Bridget A; Bernier, Francois P; Brudno, Michael; Knoppers, Bartha; Marcadier, Janet; Dyment, David; Adam, Shelin; Bulman, Dennis E; Jones, Steve J M; Avard, Denise; Nguyen, Minh Thu; Rousseau, Francois; Marshall, Christian; Wintle, Richard F; Shen, Yaoqing; Scherer, Stephen W; Friedman, Jan M; Michaud, Jacques L; Boycott, Kym M
Inherited monogenic disease has an enormous impact on the well-being of children and their families. Over half of the children living with one of these conditions are without a molecular diagnosis because of the rarity of the disease, the marked clinical heterogeneity, and the reality that there are thousands of rare diseases for which causative mutations have yet to be identified. It is in this context that in 2010 a Canadian consortium was formed to rapidly identify mutations causing a wide spectrum of pediatric-onset rare diseases by using whole-exome sequencing. The FORGE (Finding of Rare Disease Genes) Canada Consortium brought together clinicians and scientists from 21 genetics centers and three science and technology innovation centers from across Canada. From nation-wide requests for proposals, 264 disorders were selected for study from the 371 submitted; disease-causing variants (including in 67 genes not previously associated with human disease; 41 of these have been genetically or functionally validated, and 26 are currently under study) were identified for 146 disorders over a 2-year period. Here, we present our experience with four strategies employed for gene discovery and discuss FORGE's impact in a number of realms, from clinical diagnostics to the broadening of the phenotypic spectrum of many diseases to the biological insight gained into both disease states and normal human development. Lastly, on the basis of this experience, we discuss the way forward for rare-disease genetic discovery both in Canada and internationally.
Ionita-Laza, Iuliana; Ottman, Ruth
The recent progress in sequencing technologies makes possible large-scale medical sequencing efforts to assess the importance of rare variants in complex diseases. The results of such efforts depend heavily on the use of efficient study designs and analytical methods. We introduce here a unified framework for association testing of rare variants in family-based designs or designs based on unselected affected individuals. This framework allows us to quantify the enrichment in rare disease variants in families containing multiple affected individuals and to investigate the optimal design of studies aiming to identify rare disease variants in complex traits. We show that for many complex diseases with small values for the overall sibling recurrence risk ratio, such as Alzheimer's disease and most cancers, sequencing affected individuals with a positive family history of the disease can be extremely advantageous for identifying rare disease variants. In contrast, for complex diseases with large values of the sibling recurrence risk ratio, sequencing unselected affected individuals may be preferable.
Rakshith, K; Pai, Shivanand; Mittal, Saumya; Misri, Z; Shenoy, Nisha
... 5 days. The weakness was distal as well as proximal. The patient also turned out to be a case of Hansen's disease. This was detected approximately 2 months before his presentation to the hospital as a result of ulceration of the foot. He was off treatment because of gastric ulcerations. There was no other significant medical history. The pati...
Full Text Available Systemic sclerosis (also called as Scleroderma or hidebound disease is a chronic sclerotic disease of unknown etiology which causes diffuse, increased deposition of extra cellular matrix in connective tissue with vascular abnormalities, resulting in tissue hypoxia. The disease is characterized by diffuse fibrosis; degenerative changes; and vascular abnormalities in the skin (scleroderma, articular structures, and internal organs. Aesthetic and facial dysfunctions are followed by important oral and facial manifestations. Most oral manifestations begin with tongue rigidity and facial skin changes. Bone resorption of mandibular angle and widening of periodontal ligament space on periapical radiographs are important radiological findings. Other systemic changes include the involvement of internal organs, which lead to serious complications as well as disorders in the cardiac muscle and Raynaud΄s phenomenon. This is a case report of 30-year-old female patient with the classical features of this disease. This case is reported for its rarity and variable expressivity. The main aim of this article is to describe thorough presentation of the case report, various forms of scleroderma, pathogenesis, oral, extraoral, periodontal manifestations of scleroderma, and its treatment options. A brief review of the literature, focusing on dental alterations is also presented.
Khoja, Amir M; Jalan, Rahul K; Jain, Dheeraj L; Kajale, Omkar V
Osler-Weber-Rendu disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant condition causing systemic fibrovascular dysplasia. It has an incidence of 1-2/100,000. Phenotypic variation is extreme ranging from asymptomatic to severely symptomatic, from cases with no or few mucocutaneous lesions to those with diffuse cutaneous telangiectasia. We discuss a case of Osler-Weber-Rendu disease causing diffuse cutaneous telangiectasia and hemoptysis. The patient presented with complaints of hemoptysis and was extensively examined and investigated before being diagnosed with Osler-Weber-Rendu disease. We successfully managed the patient's hemoptysis by bronchial artery embolization. This case emphasizes the need for careful examination and investigation and to consider such rare diseases when all the common causes of hemoptysis are ruled out. An early and proper diagnosis will lead to more effective management of such a rare disease with few treatment options available.
Amir M Khoja
Full Text Available Osler-Weber-Rendu disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant condition causing systemic fibrovascular dysplasia. It has an incidence of 1-2/100,000. Phenotypic variation is extreme ranging from asymptomatic to severely symptomatic, from cases with no or few mucocutaneous lesions to those with diffuse cutaneous telangiectasia. We discuss a case of Osler-Weber-Rendu disease causing diffuse cutaneous telangiectasia and hemoptysis. The patient presented with complaints of hemoptysis and was extensively examined and investigated before being diagnosed with Osler-Weber-Rendu disease. We successfully managed the patient′s hemoptysis by bronchial artery embolization. This case emphasizes the need for careful examination and investigation and to consider such rare diseases when all the common causes of hemoptysis are ruled out. An early and proper diagnosis will lead to more effective management of such a rare disease with few treatment options available.
Sjögreen, Lotta; Andersson-Norinder, Jan; Bratel, John
The aim was to study oral health and oromotor function in individuals with rare diseases. A disease is defined as rare when it affects no more than 100 individuals per million population and leads to a marked degree of disability. An affected nervous or musculoskeletal system, cognitive impairment, neuropsychiatric disorders and craniofacial malformations are common in rare diseases and may all be risk factors for oral health and oromotor function. In 1996-2008, 1,703 individuals with 169 rare diseases, aged 3-67 years, answered a questionnaire about general health, oral health and orofacial function and 1,614 participated in a clinical examination. A control group of 135 healthy children, aged 3-14 years, was also included in the study. Oral health was examined by a dentist and oromotor function by a speech-language pathologist. The participants with rare diseases were recruited via family programmes, referrals to the clinic and research projects, while the controls were randomly selected from a Swedish municipality. In the diagnosis group, 40% had moderate or severe problems coping with dental treatment, 43% were receiving specialised dental care. Difficulties related to tooth brushing were common compared with the controls. Approximately two thirds of the study group and the control group were caries free. Frontal open bite, long face and high palate were common in individuals with rare diseases compared with controls. Oromotor impairment was a frequent finding (43%) and was absent among the controls. There was a significant correlation between oromotor impairment and certain structural deviations and oral-health issues. Compared with healthy controls, individuals with rare diseases often have difficulty coping with dental treatment and managing tooth brushing. Dysmorphology and oromotor dysfunction are frequent findings in this population and they often require extra prophylactic dental care and access to specialised dental care in order to prevent oral disease.
Full Text Available Dorfman-Chanarin syndrome is a rare neutral lipid storage disorder characterized by ichthyosis, lipid vacuolations in peripheral leucocytes, and multisystem involvement. It is an autosomal recessive disorder caused by mutations in the CGI-58 gene. A total of 42 cases have been reported worldwide till February 2009 out of which 4 have been previously reported from India. We report a case of a 20-month-old male with congenital ichthyosis, organomegaly, and bilateral cryptorchidism. Examination of the peripheral smear revealed lipid vacuoles in the leucocytes consistent with Jordan′s anomaly, which was confirmed by transmission electron microscopy. Liver biopsy revealed micronodular cirrhosis with macrovesicular steatosis while skin biopsy showed ichthyosis vulgaris. Dorfman-Chanarin syndrome was diagnosed on the basis of clinical and laboratory criteria with certain unreported manifestations. Dietary modifications were instituted and followed up after 1 year with promising results. This emphasizes the importance of neonatal screening for lipid vacuolations in peripheral blood in all cases of congenital ichthyosis.
Full Text Available Context: Emphysematous cystitis (EC is a rare infection of the urinary tract that results in gas production in the bladder. It is more common in diabetic and female patients, and can be associated with more serious complications, including pyelonephritis. Case Report: We describe a case of recurrent bacterial cystitis caused by Escherichia coli (E. coli. An incidental finding in our patient of pneumaturia on computed tomography (CT scan prompted further work-up. Differential diagnoses for pneumaturia include infection, trauma, and fistula, most commonly colovesicular. The patient history ruled out trauma and CT scanning ruled out a fistula; culture of the urine then showed a bacterial load greater than 100,000 E. coli/mL. The patient was then diagnosed with EC. She was treated with ceftriaxone and released in stable condition. Conclusion: The literature was scarce when it came to diagnoses of EC based on bacterial load. We present this case to increase health care providers′ awareness of recurrent EC with a urine culture bacterial load greater than 100,000 E. coli/mL.
Antonio Adolfo Guerra Soares Brandão
Full Text Available Chronic meningococcemia is a rare clinical presentation within the spectrumof infections due to Neisseria meningitidis, which was first described in 1902.It is defined as a chronic and benign meningococcal bacteremia withoutmeningeal signs or symptoms with at least one week’s duration, characterizedby intermittent or continuous fever, polymorphic cutaneous rash, and migratoryarthropathy. The incidence is believed to be around 1:200,000 inhabitants. Itaffects predominantly young people and adults, and it is equally distributedbetween genders. Diagnosis may be challenging in the early stages of thedisease because of the difficulty in isolating Neisseria meningitidis (it reaches74% of positivity in advanced stages. Recently, the use of PCR for detectingNeisseria sp antigen in skin biopsies specimens has been considered for thoseculture-negative cases. The authors report a case of a 54-year-old femalepatient who sought medical attention for a five-day fever followed by arthralgiaand skin lesions predominantly in the lower limbs. The patient progressed toa toxemic clinical status that improved after the administration of antibiotictherapy, which consisted of oxacillin and ceftriaxone. The diagnosis of chronicmeningococcemia was performed after the isolation of Neisseria meningitidisin two different blood sample cultures. This is, to our knowledge, the firstcase of chronic meningococcemia described in Brazil (up to the writing of thisreport.
Wei-wei Wu; Xue-ying Jiang; Chang-wei Liu; Yong-jun Li; Rong Zeng
Objective To investigate the dinical characteristics and treatment strategy of lower extremity arterial occlusive disease in patients with Crohn's disease(CD).Methods Clinical information of 9 cases suffering from lower extremity arterial occlusion and CD was investigated retrospectively.Results All the cases were less than 50 years old and the most were females(8/9).Arterial occlusions occurred in either active(5/9)or inactive(4/9)stage of CD.Besides the arteries of lower extremities,other arteries could also be involved such as aorta,iliac artery,renal artery or mesentery artery.Seven cases had atherosclerotic imaging findings(4 had aortic plaques and 6 had iliac artery stenoses).Embolectomy or thromboendarterectomy were mostly performed.Four(44.4% )cases had recurrent lower limb ischemia.Conclusions Arterial occlusive disease is a rare extraintestinal manifestation of CD.A thorough inspection of aorta is necessary.Embolectomy is mostly preferred.Anticoagulation treatment is highly recommended after the operation.
Full Text Available Idiopathic nontransplant-related childhood bronchiolitis obliterans is an uncommon disease. Most patients present with chronic recurrent dyspnea, cough and wheezing, which are also features of asthma, by far a much more common condition. The present case study reports on a six-year-old girl who presented to a tertiary care centre with recurrent episodes of respiratory distress on a background of baseline tachypnea, chronic hypoxemia and exertional dyspnea. Her past medical history revealed significant lung disease in infancy, including respiratory syncytial virus bronchiolitis and repaired gastroesophageal reflux. She was treated for 'asthma exacerbations' throughout her early childhood years. Bronchiolitis obliterans was subsequently diagnosed with an open lung biopsy. She did not have sustained improvement with systemic corticosteroids, hydroxychloroquine or clarithromycin. Cardiac catheterization confirmed the presence of secondary pulmonary hypertension. Treatment options remain a dilemma for this patient because there is no known effective treatment for this condition, and the natural history is not well understood. The present case demonstrates the need for careful workup in 'atypical asthma', and the urgent need for further research into the rare lung diseases of childhood.
Ramamurthy, Mahesh Babu; Goh, Daniel Y T; Lim, Michael Teik Chung
The concept of Childhood Interstitial Lung Disease (ChILD) is relatively young. There has been tremendous progress in this field in the last decade. The key advance has been the recognition of interstitial lung diseases that are often distinct and occur mainly in infants. Diagnosis is challenging because the incidence is low and no single center in the world has enough cases to promote experience and clinical skills. This has led to formation of international groups of people interested in the field and the "Children's interstitial and diffuse lung disease research network" (ChILDRN) is one such group which contributed to the progress of this field. Clinically, these disorders overlap with those of other common respiratory disorders. Hence, clinical practice guidelines emphasize the additional role of chest imaging, genetic testing and lung biopsy in the diagnostic evaluation. Genetic testing, in particular, has shown tremendous progress in this field. Being noninvasive, it has the potential to help early recognition in a vast majority. Despite progress, definitive therapeutic modalities are still lacking and supportive care is still the backbone of management in the majority. Early recognition of the definitive diagnosis helps in the management, even if, in a significant number, it helps in avoiding unnecessary therapy. Also discussed in this article, is the pulmonary manifestation of rheumatic diseases in children. The incidence and spectrum of pulmonary involvement in rheumatic conditions vary and can be result of the primary disease or its management or due to an concurrent infection.
Jalal-ud-din, Mir; Noor, Muhammad Munir; Ali, Shadab; Ali, Rashid
Kikuchi Fujimoto Disease (KFD) or histiocytic necrotizing lymphadenitis can present with unexplained fever and lymphadenopathy. It is often mistaken for more serious conditions like malignant lymphoma or tuberculosis. First case was described by Kikuchi in Japan, very few cases have been reported in Pakistan. A middle aged female presented with fever and body aches for one month. She was investigated extensively for pyrexia of unknown origin, all of which came out to be normal except a raised ESR. Anti-tuberculous drugs were started on clinical suspicion, with no improvement after a month. Later, a detailed physical examination revealed cervical lymphadenopathy. One of the lymph nodes was excised and biopsied. The histopathology suggested Kikuchi's disease. Oral Prednisolone was started showing improvement. Her fever subsided and lymph nodes disappeared at the follow-up visit. No relapse was encountered in the subsequent visits.
Njambi, S; Huttova, M; Kovac, M; Freybergh, P F; Bauer, F; Muli, J M
Within last 25 years we have observed 20 cases of fungal meningitis and/or cerebral abscesses. Commonest etiologic agens was Candida spp. (C. albicans 9 of 20). Molds were responsible for 4 cases of brain abscess. Mortality was 50% what seems to be very high. Extremely high mortality is caused by delayed onset of therapy, severe underlying disease and multiresistant fungal organisms such as Mucorales, Fusarium solani and Aureobasidium.
Hamilton, Jodi; Mandel, Louis
Castleman disease (CD), a benign lymphoproliferative disorder that affects lymph nodes, is uncommon in children, with only approximately 100 cases published. Although 23% of pediatric CD cases are found in the neck, there is no substantial reported percentage found in the salivary glands, especially the submandibular salivary gland (SMSG). A pediatric case of CD involving the SMSG is reported because of its extreme rarity. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.
Segura-Saint-Gerons, Rafael; Toro-Rojas, Mariano; Ceballos-Salobreña, Alejandro; Aparicio-Soria, Jose Luis; Fuentes-Vaamonde, Helena
Focal epithelial hyperplasia is a benign, asymptomatic disease, occurring with very low frequency within our population. It appears as papules, principally on the lower lip, although it can also be found on the retro-commissural mucosa and tongue, and less frequently on the upper lip, gingiva and palate. We present the clinical case of a 9-year-old Saharan girl with lesions that clinically and histologically corresponded to a focal epithelial hyperplasia.
Fisioterapia en la rehabilitación cardíaca: fase de convalecencia o fase II. En la sesión de entrenamiento, la fase de esfuerzo o endurecimiento pretende aumentar la capacidad funcional, la capacidad máxima de captación de oxígeno y la capacidad aeróbica máxima del paciente.
Natalia Vyacheslavovna Pizova
Full Text Available The paper gives an update on the pathogenesis, clinical presentation, and pathomorphology of cognitive impairments (CIs in different autoimmune, endocrine, and infectious diseases, such as systemic lupus erythematosus, Sjögren's syndrome, BehНet's disease, primary angiitis of the central nervous system, polyarteritis nodosa, cryoglobulinemic vasculitis, hypothyroidism, herpetic lesion, and neurosyphilis. These patients are observed to have ischemic-hypoxic brain damage, the causes of which are free radical-induced cell injury, oxidative stress, excitation toxicity, cell necrosis and/or apoptosis, inflammation and immune disease, molecular sequestration, and cell death. There is enhanced imbalance in the pro-oxidant and antioxidant systems as cerebrovascular insufficiency progresses; as this takes place, the nerve cells are most susceptible to the induction of free radical reactions. In these cases, antioxidants that block the effects of free radicals and may potentially improve brain perfusion, by assisting the coupling of neurons and vessels, are first-choice drugs. To improve the cognitive status and to prevent the progression of CIs, it is important to build a cognitive reserve in a patient; this is largely favored by the preservation of a proactive approach to life and social bonds, as well as intellectual work.
In humans, most of the genetic variation is rare and often population-specific. Whereas the role of rare genetic variants in familial monogenic diseases is firmly established, we are only now starting to explore the contribution of this class of genetic variation to human common diseases and other complex traits. Such large-scale experiments are possible due to the development of next-generation DNA sequencing. Early findings suggested that rare and low-frequency coding variation might have a large effect on human phenotypes (eg, PCSK9 missense variants on low-density lipoprotein-cholesterol and coronary heart diseases). This observation sparked excitement in prognostic and diagnostic medicine, as well as in genetics-driven strategies to develop new drugs. In this review, I describe results and present initial conclusions regarding some of the recent rare and low-frequency variant discoveries. We can already assume that most phenotype-associated rare and low-frequency variants have modest-to-weak phenotypical effect. Thus, we will need large cohorts to identify them, as for common variants in genome-wide association studies. As we expand the list of associated rare and low-frequency variants, we can also better recognise the current limitations: we need to develop better statistical methods to optimally test association with rare variants, including non-coding variation, and to account for potential confounders such as population stratification.
Litzkendorf, Svenja; Göbel, Jens; Storf, Holger; Zeidler, Jan; Graf von der Schulenburg, Johann-Matthias
Background The importance of the Internet as a medium for publishing and sharing health and medical information has increased considerably during the last decade. Nonetheless, comprehensive knowledge and information are scarce and difficult to find, especially for rare diseases. Additionally, the quality of health or medical information about rare diseases is frequently difficult to assess for the patients and their family members. Objective The aim of this study is to assess the quality of information on the Internet about rare diseases. Additionally, the study aims to evaluate if the quality of information on rare diseases varies between different information supplier categories. Methods A total of 13 quality criteria for websites providing medical information about rare diseases were transferred to a self-disclosure questionnaire. Identified providers of information on the Internet about rare diseases were invited to fill out the questionnaire. The questionnaire contained questions about the information provider in general (eg, supplier category, information category, language, use of quality certificates, and target group) and about quality aspects that reflect the 13 quality criteria. Differences in subgroup analyses were performed using t tests. Results We identified 693 websites containing information about rare diseases. A total of 123 questionnaires (17.7%) were completely filled out by the information suppliers. For the remaining identified suppliers (570/693, 82.3%), the questionnaires were filled out by the authors based on the information available on their website. In many cases, the quality of websites was proportionally low. Furthermore, subgroup analysis showed no statistically significant differences between the quality of information provided by support group/patient organization compared to medical institution (P=.19). The quality of information by individuals (patient/relative) was significantly lower compared to information provided by support
Rare haplotypes may tag rare causal variants of common diseases; hence, detection of such rare haplotypes may also contribute to our understanding of complex disease etiology. Because rare haplotypes frequently result from common single-nucleotide polymorphisms (SNPs), focusing on rare haplotypes is much more economical compared with using rare single-nucleotide variants (SNVs) from sequencing, as SNPs are available and 'free' from already amassed genome-wide studies. Further, associated haplotypes may shed light on the underlying disease causal mechanism, a feat unmatched by SNV-based collapsing methods. In recent years, data mining approaches have been adapted to detect rare haplotype association. However, as they rely on an assumed underlying disease model and require the specification of a null haplotype, results can be erroneous if such assumptions are violated. In this paper, we present a haplotype association method based on Kullback-Leibler divergence (hapKL) for case-control samples. The idea is to compare haplotype frequencies for the cases versus the controls by computing symmetrical divergence measures. An important property of such measures is that both the frequencies and logarithms of the frequencies contribute in parallel, thus balancing the contributions from rare and common, and accommodating both deleterious and protective, haplotypes. A simulation study under various scenarios shows that hapKL has well-controlled type I error rates and good power compared with existing data mining methods. Application of hapKL to age-related macular degeneration (AMD) shows a strong association of the complement factor H (CFH) gene with AMD, identifying several individual rare haplotypes with strong signals.
Its creation builds on the existing registries as well as on the structure of health care in the Slovak Republic. With the protection of personal data in mind, the collection of data will be carried out by the National Centre of Health Information (NCHI, which will also use the existing tool in the process of creation. Thanks to the cooperation between NCHI and the Slovak Society of Medical Genetics, NCHI developed separate reporting forms on rare diseases according to OMIM (Online Mendelian Inheritance in Man and ORPHANET rare disease coding (ORPHA codes of rare diseases, and the International classification of diseases code (ICD 10. The activities also include cooperation with the existing registries (part of which are rare diseases. For example National Registry of Congenital Developmental Heart Defects, national register of neuromuscular disorders, oncologic register or register of diabetes mellitus. Gathering the information from these registries we will extend the data about rare diseases in the Slovak republic. At the international level the participation in the European Surveillance of Congenital Anomalies (EUROCAT is important.
Messiaen, Claude; Le Mignot, Loïc; Rath, Ana; Richard, Jean-Baptiste; Dufour, Eric; Ben Said, Mohamed; Jais, Jean-Philippe; Verloes, Alain; Le Merrer, Martine; Bodemer, Christine; Baujat, Geneviève; Gerard-Blanluet, Marion; Bourdon-Lanoy, Eva; Salomon, Rémi; Ayme, Ségolène; Landais, Paul
Rare diseases include a group of conditions characterized by a prevalence lower than 5 per 10,000 in the community. In France, any rare disease affects less than 30,000 patients and often much less. Three to 4% of children and 6% of the population in Europe are affected. It is a true public health stake since most diseases do not have any curative treatment. In France, the Ministry of Health has initiated a National Rare Diseases Plan. Twenty five out of 132 labelled Reference Centres (RC) decided to share a common Information System named CEMARA. It is dedicated to collect continuous and complete records of all patients presenting with a rare disease, and their follow-up. The main objective of CEMARA is to contribute to the missions of the RC regarding the registration and description of their activities, coordination of the network of their correspondents, organization of the follow-up of rare diseases, and analysis of the epidemiological patterns. A description of CEMARA is provided as well as its cooperation with Orphanet and Genatlas, and a presentation of 11803 current records collected by more than 300 health care professionals belonging to more than 70 sites.
Moliner, Antoni Montserrat
Rare diseases, including those of genetic origin, are defined by the European Union as life-threatening or chronically debilitating diseases which are of such low prevalence (less than 5 per 10,000). The specificities of rare diseases - limited number of patients and scarcity of relevant knowledge and expertise - single them out as a unique domain of very high European added-value. The legal instruments at the disposal of the European Union, in terms of the Article 152 of the Treaties of the European Union, are very limited. However a combination of instruments using the research and the pharmaceutical legal basis and an intensive and creative use of funding from the First Public Health Programme 2003-2008 and from the Second Health Programme 2008-2013 has permitted to create a solid basis that Member States have considered enough to put rare diseases in a privileged position in the health agenda. The adoption of the Commission Communication, in November 2008, and of the Council Recommendation, in June 2009, and the future adoption of the Directive on Cross-border healthcare, maybe during 2010, have created an operational framework to act in the field of rare disease with European coordination in several areas (classification and codification, European Reference Networks, orphan drugs, European Committee of Experts, etc.). In conclusion, Rare diseases is an area with enormous and practical potentialities for the European cooperation.
Maciel, Marina Gagheggi; Enokihara, Milvia Maria Simões e Silva; Seize, Maria Bandeira de Melo Paiva; Marcassi, Aline Pantano; Piazza, Christiane Affonso De Donato; Cestari, Silmara da Costa Pereira
Elastoma is a connective tissue nevus characterized by changes in elastic fibers. It can be congenital or acquired, and is usually diagnosed before puberty. Associated with osteopoikilosis, it is known as Buschke-Ollendorff syndrome. Histopathology with specific staining for elastic fibers is critical for a diagnostic conclusion. This report describes the case of a 7-year-old male patient with lesions diagnosed as elastoma, with absence of bone changes in the radiological imaging. This study aims to report the clinical presentation and histological examination of such unusual disease.
Garg, Ravinder; Kukar, Neetu; Bajwa, Sukhminder Jit Singh; Kaur, Shaminder
Cold agglutinin disease (CAgD) is a type of autoimmune hemolytic anemia which generally occurs in adults and is characterized by the presence of IgM antibodies directed against polysaccharide antigens on red blood cell surface. A 16-year-old male, having clinical picture of sepsis and anemia, presented to the Emergency Department of our Institute in an Hemodynamically unstable condition. Investigation profile revealed hemolysis due to CAgD, which responded to corticosteroids, antibiotics and supportive treatment. This case highlights the importance of recognizing this entity in such type of cases presenting with sepsis and anemia. PMID:26229347
Taudien, Stefan; Lausser, Ludwig; Giamarellos-Bourboulis, Evangelos J; Sponholz, Christoph; Schöneweck, Franziska; Felder, Marius; Schirra, Lyn-Rouven; Schmid, Florian; Gogos, Charalambos; Groth, Susann; Petersen, Britt-Sabina; Franke, Andre; Lieb, Wolfgang; Huse, Klaus; Zipfel, Peter F; Kurzai, Oliver; Moepps, Barbara; Gierschik, Peter; Bauer, Michael; Scherag, André; Kestler, Hans A; Platzer, Matthias
Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. For its clinical course, host genetic factors are important and rare genomic variants are suspected to contribute. We sequenced the exomes of 59 Greek and 15 German patients with bacterial sepsis divided into two groups with extremely different disease courses. Variant analysis was focusing on rare deleterious single nucleotide variants (SNVs). We identified significant differences in the number of rare deleterious SNVs per patient between the ethnic groups. Classification experiments based on the data of the Greek patients allowed discrimination between the disease courses with estimated sensitivity and specificity>75%. By application of the trained model to the German patients we observed comparable discriminatory properties despite lower population-specific rare SNV load. Furthermore, rare SNVs in genes of cell signaling and innate immunity related pathways were identified as classifiers discriminating between the sepsis courses. Sepsis patients with favorable disease course after sepsis, even in the case of unfavorable preconditions, seem to be affected more often by rare deleterious SNVs in cell signaling and innate immunity related pathways, suggesting a protective role of impairments in these processes against a poor disease course. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Carrilho-Ferreira, Pedro; Silva, Doroteia; de Jesus Silva, Maria; André, Rui; Varela, Manuel Gato; Diogo, António Nunes
Adult-onset Still's disease is a rare disorder with potentially severe clinical features, including cardiac involvement. This systemic inflammatory disease of unknown origin should be considered in the differential diagnosis of pericarditis, with or without pericardial effusion. Cardiac tamponade is a very rare sequela that requires an invasive approach, such as percutaneous or surgical pericardial drainage, in addition to the usual conservative therapy. The authors describe a case of adult-onset Still's disease rendered more difficult by pericarditis and cardiac tamponade, and they briefly review the literature on this entity.
Glenn, Adriana D
Families affected by rare disease experience psychosocial reactions similar to families with prevalent chronic diseases. The ability to respond and manage the condition depends on psychosocial factors. This phenomenological study of 16 mothers of children with Alagille syndrome explored their lived experience in using online health communications to manage their chronic sorrow. Data consisted of semi-structured interviews analyzed using techniques described by van Manen. Analysis yielded four essential themes: connectedness, online triggers, empowerment, and seasons of online use contributed to online communication essential to a rare disease community. Findings suggest mothers need emotional support and help accessing appropriate online resources.
Simoens, Steven; Cassiman, David; Dooms, Marc; Picavet, Eline
Orphan drugs are intended for diseases with a very low prevalence, and many countries have implemented legislation to support market access of orphan drugs. We argue that it is time to revisit the special market access status of orphan drugs. Indeed, evidence suggests that there is no societal preference for treating rare diseases. Although society appears to assign a greater value to severity of disease, this criterion is equally relevant to many common diseases. Furthermore, the criterion of equity in access to treatment, which underpins orphan drug legislation, puts more value on health improvement in rare diseases than in common diseases and implies that population health is not maximized. Finally, incentives for the development, pricing and reimbursement of orphan drugs have created market failures, including monopolistic prices and the artificial creation of rare diseases. We argue that, instead of awarding special market access status to orphan drugs, there is scope to optimize research and development (R&D) of orphan drugs and to control prices of orphan drugs by means of, for example, patent auctions, advance purchase commitments, pay-as-you-go schemes and dose-modification studies. Governments should consider carefully the right incentive strategy for R&D of orphan drugs in rare diseases.
Hendriksz, Christian J.; Anheim, Mathieu; Bauer, Peter; Bonnot, Olivier; Chakrapani, Anupam; Corvol, Jean-Christophe; de Koning, Tom J.; Degtyareva, Anna; Dionisi-Vici, Carlo; Doss, Sarah; Duning, Thomas; Giunti, Paola; Iodice, Rosa; Johnston, Tracy; Kelly, Dierdre; Kluenemann, Hans-Hermann; Lorenzl, Stefan; Padovani, Alessandro; Pocovi, Miguel; Synofzik, Matthis; Terblanche, Alta; Bergh, Florian Then; Topcu, Meral; Tranchant, Christine; Walterfang, Mark; Velten, Christian; Kolb, Stefan A.
Background: Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to unde
Sepsis patients with favorable disease course after sepsis, even in the case of unfavorable preconditions, seem to be affected more often by rare deleterious SNVs in cell signaling and innate immunity related pathways, suggesting a protective role of impairments in these processes against a poor disease course.
Angelis, Aris; Tordrup, David; Kanavos, Panos
Cost-of-illness studies, the systematic quantification of the economic burden of diseases on the individual and on society, help illustrate direct budgetary consequences of diseases in the health system and indirect costs associated with patient or carer productivity losses. In the context of the BURQOL-RD project ("Social Economic Burden and Health-Related Quality of Life in patients with Rare Diseases in Europe") we studied the evidence on direct and indirect costs for 10 rare diseases (Cystic Fibrosis [CF], Duchenne Muscular Dystrophy [DMD], Fragile X Syndrome [FXS], Haemophilia, Juvenile Idiopathic Arthritis [JIA], Mucopolysaccharidosis [MPS], Scleroderma [SCL], Prader-Willi Syndrome [PWS], Histiocytosis [HIS] and Epidermolysis Bullosa [EB]). A systematic literature review of cost of illness studies was conducted using a keyword strategy in combination with the names of the 10 selected rare diseases. Available disease prevalence in Europe was found to range between 1 and 2 per 100,000 population (PWS, a sub-type of Histiocytosis, and EB) up to 42 per 100,000 population (Scleroderma). Overall, cost evidence on rare diseases appears to be very scarce (a total of 77 studies were identified across all diseases), with CF (n=29) and Haemophilia (n=22) being relatively well studied, compared to the other conditions, where very limited cost of illness information was available. In terms of data availability, total lifetime cost figures were found only across four diseases, and total annual costs (including indirect costs) across five diseases. Overall, data availability was found to correlate with the existence of a pharmaceutical treatment and indirect costs tended to account for a significant proportion of total costs. Although methodological variations prevent any detailed comparison between conditions and based on the evidence available, most of the rare diseases examined are associated with significant economic burden, both direct and indirect.
Aimé, X; Charlet, J; Furst, F; Kuntz, P; Trichet, F; Dhombres, F
In this paper, we introduce an application of Proxima and define a new measure of proximity between two concepts present in an ontology. The approach is based on the three dimensions of a conceptualization: intention with relations between concepts, expression with terms denoting concepts, and extension with instances of concepts. This preliminary work, in the field of rare diseases, involved the Orphanet Ontology of Rare Diseases (OntoOrpha) and corpus of texts extracted from Online Inheritance in Man (OMIM). The proximity measurements are consistent with an appropriate representation of groups of diseases in the ontology, which are derived from the Orphanet classifications of rare diseases. Other semantic relations are explored and new perspectives in medical knowledge curation are proposed.
Pankratz, Nathan; Pauciulo, Michael W.; Elsaesser, Veronika E.; Marek, Diane K.; Halter, Cheryl A.; Wojcieszek, Joanne; Rudolph, Alice; Shults, Clifford W.; Foroud, Tatiana; Nichols Ph.D., William C.
Mutations in DJ-1 (PARK7) are one cause of early-onset autosomal-recessive parkinsonism. We screened for DJ-1 mutations in 93 affected individuals from the 64 multiplex Parkinson disease (PD) families in our sample that had the highest family-specific multipoint LOD scores at the DJ-1 locus. In addition to sequencing all coding exons for alterations, we used multiplex ligation-dependent probe amplification (MLPA) to examine the genomic copy number of DJ-1 exons. A known polymorphism (R98Q) was found in five PD subjects, once as a homozygote and in the other four cases as heterozygotes. No additional missense mutations and no exon deletions or duplications were detected. Our results, in combination with those of previous studies, suggest that alterations in DJ-1 are not a common cause of familial PD. PMID:16997464
Full Text Available Introduction: Acute acalculous cholecystitis (AAC occurs more frequently in critically ill patients, in the immediate postoperative period, after trauma or extensive burns. It has a high rate of morbidity and mortality. Ischemia, infection and vesicular stasis are determinants in its pathogenesis. Material and method: Retrospective study including all cases of AAC diagnosed in our pediatric intensive care unit between January 1997 and December 2012. Results: We included 7 patients, all associated with viral or bacterial infection. All of them suffered from abdominal pain, mainly localized in the right upper quadrant, jaundice and dark urine. Abdominal ultrasound showed thickening and hypervascularity of the gallbladder wall in all cases. The outcome was satisfactory without surgery in all patients. Conclusions: The clinical presentation is oligosymptomatic within severe systemic diseases. The AAC should be suspected in the appearance of any abdominal pain with jaundice/dark urine and hypertransaminasemia in patients suffering from critical or serious infections.
Sathish Kumar M, Dhipu Mathew, Thilagavathy, Aruna Shanmuganathan, Srinivasan R
Full Text Available Talcosis/ Talcpneumoconiosis is one of the rarer forms of magnesium silicate induced lung disease, It usually occurs in the fourth decade and affects people working in talc related industries like roof, shingle, pharmaceutical companies, talcum powder industries, electric ceramics, rubber industry etc. We report a case of talc pneumoconiosis/talcosis in a 51yr old male who presented with breathlessness and dry cough for the past 5 yrs and progressively worsening for the past 5 days. Who was working in a talcum powder manufacturing company for >28yrs in the packaging section. The diagnosis was possible by history, clinical examination, Chest X-ray, PFT/DLCO, HRCT chest, Bronchoscopy & Trans bronchial lung biopsy showing interstitial fibrosis.
Shi, Liang; Cui, Yazhou; Luan, Jing; Zhou, Xiaoyan; Han, Jinxiang
Rare diseases with a low prevalence are a key public health issue because the causes of those diseases are difficult to determine and those diseases lack a clearly established or curative treatment. Thus, investigating the molecular mechanisms that underlie the pathology of rare diseases and facilitating the development of novel therapies using disease models is crucial. Human induced pluripotent stem cells (iPSCs) are well suited to modeling rare diseases since they have the capacity for self-renewal and pluripotency. In addition, iPSC technology provides a valuable tool to generate patient-specific iPSCs. These cells can be differentiated into cell types that have been affected by a disease. These cells would circumvent ethical concerns and avoid immunological rejection, so they could be used in cell replacement therapy or regenerative medicine. To date, human iPSCs could have been generated from multiple donor sources, such as skin, adipose tissue, and peripheral blood. However, these cells are obtained via invasive procedures. In contrast, several groups of researchers have found that urine may be a better source for producing iPSCs from normal individuals or patients. This review discusses urinary iPSC (UiPSC) as a candidate for modeling rare diseases. Cells obtained from urine have overwhelming advantages compared to other donor sources since they are safely, affordably, and frequently obtained and they are readily obtained from patients. The use of iPSC-based models is also discussed. UiPSCs may prove to be a key means of modeling rare diseases and they may facilitate the treatment of those diseases in the future.
Full Text Available El propósito de esta investigación es analizar y valorar la capacidad de realizar esfuerzos de los snowboarders, en una prueba específica. Evaluaremos dicha capacidad de trabajo individual a través de la Frecuencia cardiaca (FC, del Esfuerzo Percibido (REP y del Nivel de Fatiga Percibida (NFP, en la modalidad de Half-Pipe. Se trata de un estudio descriptivo, valorativo y correlacional de diseño cuasiexperimental unifactorial multivariado, con una muestra de n=5 sujetos, que constituyen la totalidad del equipo Olímpico español de Snowboard. La prueba diseñada ad hoc se ha realizado a 3.000 m. en el glaciar de Tignes. Las conclusiones de este estudio demuestran 1 que es posible realizar una investigación de campo en la que se cuantifique la intensidad de la tarea, y 2 que para valorar el esfuerzo debemos combinar variables fisiológicas y psicológicas. Finalmente se plantea la importancia del Nivel de Fatiga Percibida, como instrumento predictivo en el proceso de toma de decisiones.
Full Text Available Gastrointestinal duplication is a rare congenital disease which affected more commonly the ileum, while the stomach is rarely involved. Generally diagnosed in paediatric or young age, it could be difficult to suspect a gastrointestinal duplication in adults. Herein, we report a 55-year-old male with a gastric duplication cyst found on routinely checkup for chronic hepatitis and first misdiagnosed as a gastrointestinal stromal tumor (GIST; we also discuss its embryology.
Amal F Radwan
Full Text Available A 37-year-old hypertensive housewife presented with a sudden onset of left-sided hemiplegia, hemianaesthesia, dysarthria and urinary incontinence. The condition was preceded by recurrent attacks of motor neurological deficits over a 3-year duration. She reported a history of a fall from a height at the age of 10, which was followed by a hearing deficit and a history of two caesarean sections after eclampsia. The blood pressure was 170/100 mmHg. Laboratory investigations revealed hyperglycaemia (fasting glucose 306 mg/dl and normal kidney function tests. The computed tomography scans revealed old multiple bilateral cerebral infarcts with recent intracranial haemorrhage in the right parietal region. The inflammatory markers (ESR and CRP and immune profile (ANA, anti-ds DNA and ANCA were found to be normal. Cerebral angiography revealed a complete occlusion of the intracranial parts of both internal carotid arteries at their supraclinoid segments along with the proximal parts of the anterior cerebral artery and middle cerebral artery, with collaterals from the posterior circulation. Consequently, the diagnosis of moyamoya disease with the collaterals was confirmed. Antihypertensive medications and insulin were administered. Cerebral dehydration measures were undertaken with partial improvement. A superficial temporal artery-middle cerebral artery bypass operation was performed with some postoperative improvement. One month later, she suffered a new stroke with severe impairment of the level of consciousness; the computed tomography scans revealed a large recent cerebral infarct, her condition deteriorated rapidly and she died shortly thereafter.
Gucev, Z; Tasic, V; Polenakovic, M
The Second meeting on Rare Diseases in South Eastern Europe (SEE) was held in Skope, Macedonia on November 15-16, 2013. Objective and main data: Rare diseases (RD) are a major problem in developed and especially in countries without affluence. 6-8% of every population suffers from RD. The cumulative effect of RDs on the health system of a country is increasing. Diagnosis often remains a challenge and requires international collaboration. Treatment in diseases for which medication exist is often inaccessible to patients because of the high costs. All countries of SEE need screening programs that address more diseases. Patient organizations play a major role in increasing awareness and providing the needed pressure on society to treat treatable RDs. On the other hand, RDs are frequently a source of valuable new molecular insights not only on mechanisms of their etiology and pathology, but sometimes provide an insight on mechanisms of frequent diseases in man. Further efforts are needed in improving all the RD aspects mentioned.
N. A. Shostak
Full Text Available Chronic thromboembolic pulmonary hypertension (CTEPH is a rare life-threatening disease with a prevalence of 2 cases per 100000 population. CTEPH is a chronic, progressive disease characterized by high disability and mortality rates in young and middle-aged people, often with underlying genetic and autoimmune thrombophilic disorders. The need for pathogenetic therapy with orphan drugs that can slow the progression of the disease is supported.
Full Text Available Kikuchi-Fujimoto disease (KFD or histiocytic necrotizing lymphadenitis is a rare, benign, self-limiting disease with unknown etiology characterized by regional lymphadenopathy. A 30-year-old female presented with fever, weakness, multiple joint pain, oral ulcers, erythematous facial rashes, hemorrhagic crusting on both lips, and cervical lymphadenopathy of 2-month duration. Clinically, the disease was mimicking systemic lupus erythematosus, but immunofluorescence was negative for it. Lymph node biopsy suggested a diagnosis of KFD.
de Souza, Mônica Vinhas; Krug, Bárbara Corrêa; Picon, Paulo Dornelles; Schwartz, Ida Vanessa Doederlein
This paper approaches in a critical way aspects of Brazilian public policies for drugs, emphasizing those classified as high cost and for rare diseases. The lysosomal storage diseases was taken as an example because of their rarity and the international trend for the development of new drugs for their treatment, all at high costs. Three lysosomal storage diseases were approached: Gaucher disease, Fabry disease and mucopolysaccharidosis type I. Gaucher disease has its treatment drug licensed in Brazil and guidelines for its use are established through a clinical protocol by the Ministry of Health. The others have their drug treatments registered in Brazil; however, no treatment guidelines for them have been developed by the government. The objective of the paper was to foster the discussion on the role of health technology assessment for high-cost drugs for rare diseases in Brazil, emphasizing the need for establishing health policies with legitimacy towards these diseases. Despite the difficulties in establishing a health policy for each rare disease, it is possible to create rational models to deal with this growing challenge.
Greene, Daniel; Richardson, Sylvia; Turro, Ernest
Rare genetic disorders, which can now be studied systematically with affordable genome sequencing, are often caused by high-penetrance rare variants. Such disorders are often heterogeneous and characterized by abnormalities spanning multiple organ systems ascertained with variable clinical precision. Existing methods for identifying genes with variants responsible for rare diseases summarize phenotypes with unstructured binary or quantitative variables. The Human Phenotype Ontology (HPO) allows composite phenotypes to be represented systematically but association methods accounting for the ontological relationship between HPO terms do not exist. We present a Bayesian method to model the association between an HPO-coded patient phenotype and genotype. Our method estimates the probability of an association together with an HPO-coded phenotype characteristic of the disease. We thus formalize a clinical approach to phenotyping that is lacking in standard regression techniques for rare disease research. We demonstrate the power of our method by uncovering a number of true associations in a large collection of genome-sequenced and HPO-coded cases with rare diseases. PMID:26924528
Taylor, Colman; Jan, Stephen; Thompson, Kelly
Funding rare disease therapies presents a challenge in Australia where there is a legislative requirement to consider cost-effectiveness. Currently the Life Saving Drugs Programme (LSDP) provides subsidised access to high-cost therapies for rare, life-threatening conditions. However the LSDP is currently under review by the Minsiter for Health and future access to rare disease therapies in uncertain. Internationally there is no gold standard model to evaluate and fund rare disease therapies, and considerable variation exists. However, common features of international systems include the opportunity for early stakeholder engagement, flexibility with evidence requirements, cost-effectiveness criteria and transparency in relation to the decision making framework and outcomes. Australians value equality and equal opportunity in relation to health care. To meet these expectations there is a clear need to maintain a separate fit-for-purpose framework to evaluate and fund rare disease therapies drawing on overseas best practice. This will provide certainty for industry to continue to invest in such treatments, as well as ensuring funding recommendations are reflective of Australian values balanced against the need for financial sustainability.
Full Text Available The rapid advances in sequencing technologies and the resulting next-generation sequencing data provide the opportunity to detect disease-associated variants with a better solution, in particular for low-frequency variants. Although both common and rare variants might exert their independent effects on the risk for the trait of interest, previous methods to detect the association effects rarely consider them simultaneously. We proposed a class of test statistics, the generalized weighted-sum statistic (GWSS, to detect disease associations in the presence of common and rare variants with a case-control study design. Information of rare variants was aggregated using a weighted sum method, while signal directions and strength of the variants were considered at the same time. Permutations were performed to obtain the empirical p-values of the test statistics. Our simulation showed that, compared to the existing methods, the GWSS method had better performance in most of the scenarios. The GWSS (in particular VDWSS-t method is particularly robust for opposite association directions, association strength, and varying distributions of minor-allele frequencies. It is therefore promising for detecting disease-associated loci. For empirical data application, we also applied our GWSS method to the Genetic Analysis Workshop 17 data, and the results were consistent with the simulation, suggesting good performance of our method. As re-sequencing studies become more popular to identify putative disease loci, we recommend the use of this newly developed GWSS to detect associations with both common and rare variants.
Greene, Daniel; Richardson, Sylvia; Turro, Ernest
Rare genetic disorders, which can now be studied systematically with affordable genome sequencing, are often caused by high-penetrance rare variants. Such disorders are often heterogeneous and characterized by abnormalities spanning multiple organ systems ascertained with variable clinical precision. Existing methods for identifying genes with variants responsible for rare diseases summarize phenotypes with unstructured binary or quantitative variables. The Human Phenotype Ontology (HPO) allows composite phenotypes to be represented systematically but association methods accounting for the ontological relationship between HPO terms do not exist. We present a Bayesian method to model the association between an HPO-coded patient phenotype and genotype. Our method estimates the probability of an association together with an HPO-coded phenotype characteristic of the disease. We thus formalize a clinical approach to phenotyping that is lacking in standard regression techniques for rare disease research. We demonstrate the power of our method by uncovering a number of true associations in a large collection of genome-sequenced and HPO-coded cases with rare diseases.
Full Text Available Crohn’s disease is a granulomatous inﬂammatory bowel disease. Its pathologic ﬁndings include non-contiguous chronic inﬂammation and non-caseating granulomas, sometimes with extra-intestinal localizations. Sinonasal manifestations of Crohn’s disease are quite rare and only a few cases have been reported up to date in the worldwide literature. They are characterized by chronic mucosal inﬂammation, obstruction, bleeding and occasionally septal perforation. We report a case of sinonasal granulomatosis revealing Crohn’s disease in a 22-year-old woman and go over the available literature on sinonasal involvement in Crohn’s disease.
Choquet, Rémy; Maaroufi, Meriem; de Carrara, Albane; Messiaen, Claude; Luigi, Emmanuel; Landais, Paul
Background Although rare disease patients make up approximately 6–8% of all patients in Europe, it is often difficult to find the necessary expertise for diagnosis and care and the patient numbers needed for rare disease research. The second French National Plan for Rare Diseases highlighted the necessity for better care coordination and epidemiology for rare diseases. A clinical data standard for normalization and exchange of rare disease patient data was proposed. The original methodology used to build the French national minimum data set (F-MDS-RD) common to the 131 expert rare disease centers is presented. Methods To encourage consensus at a national level for homogeneous data collection at the point of care for rare disease patients, we first identified four national expert groups. We reviewed the scientific literature for rare disease common data elements (CDEs) in order to build the first version of the F-MDS-RD. The French rare disease expert centers validated the data elements (DEs). The resulting F-MDS-RD was reviewed and approved by the National Plan Strategic Committee. It was then represented in an HL7 electronic format to maximize interoperability with electronic health records. Results The F-MDS-RD is composed of 58 DEs in six categories: patient, family history, encounter, condition, medication, and questionnaire. It is HL7 compatible and can use various ontologies for diagnosis or sign encoding. The F-MDS-RD was aligned with other CDE initiatives for rare diseases, thus facilitating potential interconnections between rare disease registries. Conclusions The French F-MDS-RD was defined through national consensus. It can foster better care coordination and facilitate determining rare disease patients’ eligibility for research studies, trials, or cohorts. Since other countries will need to develop their own standards for rare disease data collection, they might benefit from the methods presented here. PMID:25038198
Koti, Kalyan; Thumma, Rayapa Reddy; Nagarajan, Swathanthra; Mathi, Atchyuta
Evans syndrome is a rare combination of autoimmune hemolytic anemia and immune thrombocytopenia. Their association with autoimmune thyroid diseases has been reported by few authors; however, a sequential development of the Evans syndrome in cases of Hashimoto's thyroiditis is extremely rare. The clustering of these autoimmune diseases might share a common pathogenic pathway. We present the fourth such case in world literature, of a 34-year-old female diagnosed with Hashimoto's thyroiditis in 2006, who has been taking synthetic thyroid hormone since then. Her condition is now clinically complicated with the development of the Evans syndrome.
The wealth of available genetic information is allowing the reconstruction of human demographic and adaptive history. Demography and purifying selection affect the purge of rare, deleterious mutations from the human population, whereas positive and balancing selection can increase the frequency of advantageous variants, improving survival and reproduction in specific environmental conditions. In this review, I discuss how theoretical and empirical population genetics studies, using both modern and ancient DNA data, are a powerful tool for obtaining new insight into the genetic basis of severe disorders and complex disease phenotypes, rare and common, focusing particularly on infectious disease risk.
Abhiram Chakrabarti; Manab Nandy; Dipankar Pal; Sudesna Mallik
Leptospirosis, a disease of protean manifestations occurs sporadically throughout the year with a peak seasonal incidence during the rainy season mimicking other febrile viral illness. In the rare case, the disease leads to renal and hepatic involvement with hemorrhage which may be associated with multisystem organ dysfunction in form of pulmonary, cardiac and central nervous system, when it is known as Weil’s disease. Rarely haemorrhagic manifestations are assosciated. Early diagnosis is important as sometimes the disease may be life threatening. Proper antibiotics results in dramatic improvement. We hereby presented a case that had clinical features of Weil’s disease with cough, dyspnoea and haemoptysis. Leptospirosis was detected on ELISA testing. Patient was cured rapidly with antibiotics.
Blöß, Susanne; Klemann, Christian; Rother, Ann-Katrin; Mehmecke, Sandra; Schumacher, Ulrike; Mücke, Urs; Mücke, Martin; Stieber, Christiane; Klawonn, Frank; Kortum, Xiaowei; Lechner, Werner; Grigull, Lorenz
Background Worldwide approximately 7,000 rare diseases have been identified. Accordingly, 4 million individuals live with a rare disease in Germany. The mean time to diagnosis is about 6 years and patients receive several incorrect diagnoses during this time. A multiplicity of factors renders diagnosing a rare disease extremely difficult. Detection of shared phenomena among individuals with different rare diseases could assist the diagnostic process. In order to explore the demand for diagnostic support and to obtain the commonalities among patients, a nationwide Delphi survey of centers for rare diseases and patient groups was conducted. Methods A two-step Delphi survey was conducted using web-based technologies in all centers for rare diseases in Germany. Moreover, the leading patient support group, the German foundation for rare diseases (ACHSE), was contacted to involve patients as experts in their disease. In the survey the experts were invited to name rare diseases with special need for diagnostic improvement. Secondly, communal experiences of affected individuals were collected. Results 166 of 474 contacted experts (35%) participated in the first round of the Delphi process and 95 of 166 (57%) participated in the second round. Metabolic (n = 74) and autoimmune diseases (n = 39) were ranked the highest for need for diagnostic support. For three diseases (i.e. scleroderma, Pompe’s disease, and pulmonary arterial hypertension), a crucial need for diagnostic support was explicitly stated. A typical experience of individuals with a rare disease was stigmatization of having psychological or psychosomatic problems. In addition, most experts endured an ‘odyssey’ of seeing many different medical specialists before a correct diagnosis (n = 38) was confirmed. Conclusion There is need for improving the diagnostic process in individuals with rare diseases. Shared experiences in individuals with a rare disease were observed, which could possibly be utilized for
... muscular dystrophies; Huntington's disease, a hereditary chorea; myoclonus; Tourette's syndrome; and... drugs for rare diseases or conditions. 1.28-1 Section 1.28-1 Internal Revenue INTERNAL REVENUE SERVICE... clinical testing expenses for certain drugs for rare diseases or conditions. (a) General rule. Section 28...
Forloni, Gianluigi; Tettamanti, Mauro; Lucca, Ugo; Albanese, Yasmin; Quaglio, Elena; Chiesa, Roberto; Erbetta, Alessandra; Villani, Flavio; Redaelli, Veronica; Tagliavini, Fabrizio; Artuso, Vladimiro; Roiter, Ignazio
Abstract The text describes a preventive clinical trial with drug treatment in a very rare neurodegenerative disease (Fatal familial Insomnia, FFI) designed with the help of individuals at genetic risk of developing the disease, asymptomatic carriers, who have agreed to be exposed over a 10-year period to doxycycline, an antibiotic with anti-prion activity. At least 10 carriers of the FFI mutation over 42 y old will be treated with doxycycline (100 mg/die) and the incidence of the disease will be compared to that of an historical dataset. For ethical reasons a randomized, double-blind, placebo-controlled trial was not feasible, however the study design and the statistical analysis ensure the scientific value of the results. This approach might represent an important breakthrough in terms of potential therapy and knowledge of rare diseases that could give some hopes to these neglected patients. PMID:25996399
Katavic, Snježana Stanarevic; Tanackovic, Sanjica Faletar; Badurina, Boris
Introduction: This study examined possible correlations between health information behaviour and illness perception among patients with rare chronic diseases. Illness perception is related to coping strategies used by patients, and some health information behaviour practices may be associated with better coping and more positive perception of…
M. Scarpa (Maurizio); Z. Almássy (Zsuzsanna); M. Beck (Michael); O.A. Bodamer (Olaf); I.A. Bruce (Iain); L. de Meirleir (Linda); N. Guffon (Nathalie); E. Guillen-Navarro (Encarna); P. Hensman (Pauline); S. Jones (Simon); W. Kamin (Wolfgang); C. Kampmann (Christoph); C. Lampe (Christina); C.A. Lavery (Christine); E. Leão Teles (Elisa); B. Link (Bianca); A.M. Lund (Allan); G. Malm (Gunilla); S. Pitz (Susanne); M. Rothera (Michael); C. Stewart (Catherine); A. Tylki-Szymaska (Anna); A.T. van der Ploeg (Ans); R. Walker (Robert); J. Zeman (Jiri); J.E. Wraith (James)
textabstractMucopolysaccharidosis type II (MPS II) is a rare, life-limiting, X-linked recessive disease characterised by deficiency of the lysosomal enzyme iduronate-2-sulfatase. Consequent accumulation of glycosaminoglycans leads to pathological changes in multiple body systems. Age at onset, signs
Mariampillai, Anusiyanthan; Sivapiragasam, Abirami; Kumar, Amit; Hindenburg, Alexander; Cunha, Burke A; Zhou, Jianhong
We report the case of a patient with recurrent fever of unknown origin (FUO) with prominent back pain, hepatosplenomegaly, and abdominal/pelvic adenopathy suggesting lymphoma. A bone biopsy showed histiocytic infiltration. Studies for lymphoma were negative, but immunohistochemical stains were diagnostic of Erdheim-Chester disease (ECD). ECD should be included as a rare cause of recurrent FUO with bone involvement.
Bala, Senduran; Clapham, Peter; Coates, Guy
The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively pheno...
Full Text Available Balantidiasis is a rare zoonotic disease in humans. Balantidium coli is the causative ciliated protozoan. We present a case of urinary balantidiasis in a patient having chronic obstructive pulmonary disease (COPD who was on steroids for a long time. He has no symptoms of bowel or urinary involvement. We are reporting this case because of its rarity in human urine and also for future references.
Full Text Available Castleman′s Disease (CD is an uncommon and poorly understood disorder of lymph node hyperplasia of unknown etiology. This entity belongs to the atypical lymphoproliferative disorders, a heterogeneous group of diseases characterized by a hyperplastic reactive process involving the immune system. The association of the nephrotic syndrome and CD is extremely rare and their interrelation remains enigmatic. We report a case of CD of the hyaline-vascular type with unicentric localization complicated by nephrotic syndrome.
Tripathy KP, Behera PK, Dalai RK, Misra GC
Fahr’s disease or Fahr’s syndrome is a rare neurological disorder characterized by abnormal calcified deposits in the basal ganglia and cerebral cortex. 47 years male who presented to us with progressive ataxia and Parkinsonian symptoms was found to have extensive bilateral calcifications including bilateral basal ganglia in CT scan of the brain. The secondary causes of intracranial calcifications were ruled out to make a clinical diagnosis of Fahr’s disease. While investigating for chronic...
Wandel, Simon; Neuenschwander, Beat; Friede, Tim; Röver, Christian
Clinical research and drug development in orphan diseases is challenging, since large-scale randomized studies are difficult to conduct. Formally synthesizing the evidence is therefore of great value, yet this is rarely done in the drug approval process. Phase III designs that make better use of phase II data can facilitate drug development in orphan diseases. A Bayesian meta-analytic approach is used to inform the phase III study with phase II data. It is particularly attractive, since uncer...
Rollet, Pierrick; Lemoine, Adrien; Dunoyer, Marc
Legislative incentives enacted in Europe through the Regulation (EC) No. 141/2000 to incentivize orphan drug development have over the last 12 years constituted a powerful impetus toward R&D directed at the rare diseases population. However, despite therapeutic promises contained in these projects and significant economic impact linked to burgeoning R&D expenditures, the affordability and value of OMPs has become a topic of health policy debate in Europe fueled by the perception that OMPs have high acquisition costs, and by misconceptions around pricing dynamics and rare-diseases business models. In order to maintain sustainable patient access to new and innovative therapies, it is essential to address these misconceptions, and to ensure the successful continuation of a dynamic OMPs R&D within rare-diseases public health policy. Misconceptions abound regarding the pricing of rare diseases drugs and reflect a poor appreciation of the R&D model and the affordability and value of OMPs. Simulation of potential financial returns of small medium sized rare diseases companies focusing on high priced drugs show that their economic returns are likely to be close to their cost of capital. Research in rare diseases is a challenging endeavour characterised by high fixed costs in which companies accrue substantial costs for several years before potentially generating returns from the fruits of their investments. Although heavily dependent upon R&D capabilities of each individual company or R&D organization, continuous flow of R&D financial investment should allow industry to increasingly include efficiencies in research and development in cost considerations to its customers. Industry should also pro-actively work on facilitating development of a specific value based pricing approach to help understanding what constitute value in rare diseases. Policy makers must reward innovation based upon unmet need and patient outcome. Broader understanding by clinicians, the public, and
Manna, Raffaele; Cauda, Roberto; Feriozzi, Sandro; Gambaro, Giovanni; Gasbarrini, Antonio; Lacombe, Didier; Livneh, Avi; Martini, Alberto; Ozdogan, Huri; Pisani, Antonio; Riccio, Eleonora; Verrecchia, Elena; Dagna, Lorenzo
Fever of unknown origin (FUO) is a rather rare clinical syndrome representing a major diagnostic challenge. The occurrence of more than three febrile attacks with fever-free intervals of variable duration during 6 months of observation has recently been proposed as a subcategory of FUO, Recurrent FUO (RFUO). A substantial number of patients with RFUO have auto-inflammatory genetic fevers, but many patients remain undiagnosed. We hypothesize that this undiagnosed subgroup may be comprised of, at least in part, a number of rare genetic febrile diseases such as Fabry disease. We aimed to identify key features or potential diagnostic clues for Fabry disease as a model of rare genetic febrile diseases causing RFUO, and to develop diagnostic guidelines for RFUO, using Fabry disease as an example of inserting other rare diseases in the existing FUO algorithms. An international panel of specialists in recurrent fevers and rare diseases, including internists, infectious disease specialists, rheumatologists, gastroenterologists, nephrologists, and medical geneticists convened to review the existing diagnostic algorithms, and to suggest recommendations for arriving at accurate diagnoses on the basis of available literature and clinical experience. By combining specific features of rare diseases with other diagnostic considerations, guidelines have been designed to raise awareness and identify rare diseases among other causes of FUO. The proposed guidelines may be useful for the inclusion of rare diseases in the diagnostic algorithms for FUO. A wide spectrum of patients will be needed to validate the algorithm in different clinical settings.
Narayana Gowda BS
Full Text Available Introduction: Hirayama’s disease is a rare benign disorder, also referred to as monomelic amyotrophy (MMA, Juvenile non progressive amyotrophy, Sobue disease. It is a focal, lower motor neuron type of disease. Mainly young males in their second and third decades of age are most commonly affected. It is seen most commonly in Asian countries like India and Japan. In majority of people cause of this disease is unknown. MRI of cervical spine in flexion will reveal the cardinal features of Hirayama disease. Case Report: A 22 year gentleman came with a history of insidious onset of weakness in both the hands begenning with left side followed by right of 4 years duration. On examination he had clawing of both hands with wasting of forearm muscles. Lower limbs had no abnormality with normal deep tendon reflexes. MRI showed thinning of cord from C4 to C7 level suggestive of cord atrophy. Based on these features a diagnosis of focal amyotrophy was made. A cervical collar was prescribed and patient is under regular follow up. Conclusion: Hirayama disease is a rare self-limiting disease. Early diagnosis is necessary as the use of a simple cervical collar which will prevent neck flexion, has been shown to stop the progression. Keywords: Hirayama’s disease, monomelic amyotrophy, Juvenile non-progressive amyotrophy, Sobue disease.
Groza, Tudor; Köhler, Sebastian; Moldenhauer, Dawid; Vasilevsky, Nicole; Baynam, Gareth; Zemojtel, Tomasz; Schriml, Lynn Marie; Kibbe, Warren Alden; Schofield, Paul N.; Beck, Tim; Vasant, Drashtti; Brookes, Anthony J.; Zankl, Andreas; Washington, Nicole L.; Mungall, Christopher J.; Lewis, Suzanna E.; Haendel, Melissa A.; Parkinson, Helen; Robinson, Peter N.
The Human Phenotype Ontology (HPO) is widely used in the rare disease community for differential diagnostics, phenotype-driven analysis of next-generation sequence-variation data, and translational research, but a comparable resource has not been available for common disease. Here, we have developed a concept-recognition procedure that analyzes the frequencies of HPO disease annotations as identified in over five million PubMed abstracts by employing an iterative procedure to optimize precision and recall of the identified terms. We derived disease models for 3,145 common human diseases comprising a total of 132,006 HPO annotations. The HPO now comprises over 250,000 phenotypic annotations for over 10,000 rare and common diseases and can be used for examining the phenotypic overlap among common diseases that share risk alleles, as well as between Mendelian diseases and common diseases linked by genomic location. The annotations, as well as the HPO itself, are freely available. PMID:26119816
Sjögreen, L; Mogren, Å; Andersson-Norinder, J; Bratel, J
The aim was to study the background to and the manifestations of affected intelligibility of speech and reported difficulty with eating and saliva control in rare diseases. In Sweden, a disease or disorder is defined as rare when it affects no more than 100 individuals per million population and leads to a marked degree of disability. In 1996-2008, 1703 individuals with 169 rare diseases (3-67 years) answered a questionnaire about oral health and oro-facial function and 1614 participated in a clinical examination. A control group of 135 healthy children was included. Oromotor impairment was a frequent finding (43%) and was absent among the controls. Half the children in the youngest age group (3-6 years) had moderate/severely affected intelligibility or no speech compared with one-third in the other age groups. The most frequent eating difficulties were related to chewing and were found in approximately 20% of the individuals in the study group. Artificial nutrition was most common in children aged 3-6 years (9·2%), followed by children aged 7-12 years (4·9%), adolescents aged 13-19 years (3·3%) and adults (1·4%). Impaired saliva control was common (31·2%) and strongly and significantly correlated with oromotor dysfunction, intellectual disability, open mouth at rest and epilepsy. In conclusion, oromotor impairment and oro-facial dysfunctions, such as affected intelligibility, eating difficulties and impaired saliva control, are frequent in individuals with rare diseases. There is a strong correlation between oromotor impairment and affected intelligibility, eating difficulties and impaired saliva control in individuals with rare diseases.
Gucev, Zoran; Tasic, Velibor; Polenakovic, Momir
The 4th meeting on rare diseases in South Eastern Europe (SEE) was held in Skopje, at the Macedonian Academy of Sciences and Arts (MASA) on the 14(th) of November 2015. The focuses were metabolic, rare brain diseases as well as the rare dysmorphic syndrome. The authors of the report are particularly keen on stating that one of the main goals of the meeting, namely to help the treatment of patients with rare disease has begun to bear fruits. The talk on an iminosugar-based pharmacological chaperone compound as a drug candidate for the treatment of GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B) was enlightening. To date, there is no treatment available to be offered to patients, but chaperones lead mutated proteins to adopt a native-like conformation and to successfully traffic to their normal cellular destination. DORPHAN is developing an iminosugar-based pharmacological chaperone compound for the treatment of GM1-gangliosidosis and mucopolysaccharidosis IVB. A talk on recent developments in the laboratory diagnosis of mucopolysaccharidoses (MPS) was particularly interesting, covering the laboratory diagnosis of the MPS diseases by a strategy of clinical examination, biochemical analysis of urine samples, enzyme tests and genetic characterization of underlying mutations. New techniques were developed, including analysis of urinary glycosaminoglycans with tandem mass spectrometry, miniaturized enzyme tests or novel synthetic substrates for enzyme assays using mass spectrometry detection of products using dried blood spots. Feasibility and cost-effectiveness of these methods in newborn screening programs have been demonstrated. Neuromuscular RDs, and especially familial amyloid polyneuropathy (FAP) were a topic of the Bulgarian colleagues. Diagnosis, screening and the role of microglia were also topics of particular interest. In summary, this year RD meeting was exciting and productive on a wide range of diseases and on a novel insights on
Mägi, Reedik; Asimit, Jennifer L; Day-Williams, Aaron G; Zeggini, Eleftheria; Morris, Andrew P
Genome-wide association studies have been successful in identifying loci contributing effects to a range of complex human traits. The majority of reproducible associations within these loci are with common variants, each of modest effect, which together explain only a small proportion of heritability. It has been suggested that much of the unexplained genetic component of complex traits can thus be attributed to rare variation. However, genome-wide association study genotyping chips have been designed primarily to capture common variation, and thus are underpowered to detect the effects of rare variants. Nevertheless, we demonstrate here, by simulation, that imputation from an existing scaffold of genome-wide genotype data up to high-density reference panels has the potential to identify rare variant associations with complex traits, without the need for costly re-sequencing experiments. By application of this approach to genome-wide association studies of seven common complex diseases, imputed up to publicly available reference panels, we identify genome-wide significant evidence of rare variant association in PRDM10 with coronary artery disease and multiple genes in the major histocompatibility complex (MHC) with type 1 diabetes. The results of our analyses highlight that genome-wide association studies have the potential to offer an exciting opportunity for gene discovery through association with rare variants, conceivably leading to substantial advancements in our understanding of the genetic architecture underlying complex human traits.
Full Text Available Table of contents O1 The European Social Preferences Measurement (ESPM study project: social cost value analysis, budget impact, commercial life cycle revenue management, and the economics of biopharmaceutical Research & Development (R&D Michael Schlander, Søren Holm, Erik Nord, Jeff Richardson, Silvio Garattini, Peter Kolominsky-Rabas, Deborah Marshall, Ulf Persson, Maarten Postma, Steven Simoens, Oriol de Solà Morales, Keith Tolley, Mondher Toumi, Harry Telser O2 Newborn Screening: the potential and the challenges James R Bonham O3 Untreatable disease outcomes - how would we measure them? Helmut Hintner, Anja Diem, Martin Laimer O4 Taking Integrated Care Forward: Experiences from Canada to inspire service provision for people living with rare disease in Europe Réjean Hébert O5 Listening to the patient’s voice: social media listening for safety and benefits in rare diseases Nabarun Dasgupta, Carrie E. Pierce, Melissa Jordan O6 Via Opta: Mobile apps making visually impaired patients’ lives easier Barbara Bori, Mohanad Fors, Emilie Prazakova O7 A report of the IRDiRC “Small Population Clinical Trial” Task Force Simon Day O8 HAE patient identification and diagnosis: An innovative, ‘game changing’ collaboration Thomas J. Croce Jr. O9 Co-creating with the community: primary packaging & administration for people with haemophilia Jonas Fransson, Philip Wood O10 Go with Gaucher, taking forward the next generation. How to involve young people to create a new generation of patient advocates Anne-Grethe Lauridsen, Joanne Higgs, Vesna Stojmirova Aleksovska P1 ODAK – Orphan Drug for Acanthamoeba Keratitis Christina Olsen, Ritchie Head, Antonio Asero, Vincenzo Papa, Christa van Kan, Loic Favennec, Silvana Venturella, Michela Salvador, Alan Krol P5 Rare Navigators help people living with rare diseases to manage the social – and healthcare systems Stephanie J. Nielsen, Birthe B. Holm P6 The eAcademy for Tay-Sachs & Sandhoff disease app
Korviriyakamol, Tarinee; Kattipathananpong, Pinnaree; Chunhasewee, Chakkrapong; Wessagowit, Vesarat; Kootiratrakarn, Tanawatt
Coexisting variants of porokeratosis rarely occurs. Disseminated superficial porokeratosis (DSP) is characterized by multiple uniform small annular papules distributed all over body. DSP commonly coexist with linear porokeratosis (LP), but it is uncommon for DSP to coexist with porokeratosis of Mibelli (PM). PM presents with central atrophic erythematous plaques and thread-like elevated border. It occurs mainly on extremities. Although malignant transformation can be found in the porokeratosis, there is still no report case of coexisting variants of porokeratosis concurrent with Bowen's disease. The clinical and histopathologic finding of rare coexisting variants of porokeratosis (PM and DSP) concurrent with squamous dysplasia is described.
Mallikarjunaiah H. S.
Full Text Available Background:Hallervorden-Spatz disease (HSD is a rare neurological disease characterized by progressivedegeneration of basal ganglia, globuspallidus and reticular part of the substantianigra, produced byironaccumulation. The defect has been found in the pantothenate kinase 2 (PANK2 producing gene locatedinchromosome 20p13-p12.3. Clinical presentations include dystonia, dysarthria, dysphasia, dementia, severemental retardation and severe movement disability may develop at later stages. Rare clinical features includerigidity, choreoathetosis, seizures, optic atrophy and pigmentary retinopathy. The characteristic MRI brainpattern of HSD shows the “eye of the tiger ” pattern. Treatment is symptomatic. We present the case of apatient, 19 years old boy with Hallervorden-Spatz disease who came to our physiotherapy department withfeatures of spasticity, dystonia and gait difficulty. He was diagnosed on the basis of clinical findings and typicalMRI brain of “eye of the tiger” pattern. His detailed evaluation was carried out and physiotherapy treatmentwas started.
Mistry Pramod K
Full Text Available Abstract Background In clinical research of rare diseases, where small patient numbers and disease heterogeneity limit study design options, registries are a valuable resource for demographic and outcome information. However, in contrast to prospective, randomized clinical trials, the observational design of registries is prone to introduce selection bias and negatively impact the validity of data analyses. The objective of the study was to demonstrate the utility of case-control matching and the risk-set method in order to control bias in data from a rare disease registry. Data from the International Collaborative Gaucher Group (ICGG Gaucher Registry were used as an example. Methods A case-control matching analysis using the risk-set method was conducted to identify two groups of patients with type 1 Gaucher disease in the ICGG Gaucher Registry: patients with avascular osteonecrosis (AVN and those without AVN. The frequency distributions of gender, decade of birth, treatment status, and splenectomy status were presented for cases and controls before and after matching. Odds ratios (and 95% confidence intervals were calculated for each variable before and after matching. Results The application of case-control matching methodology results in cohorts of cases (i.e., patients with AVN and controls (i.e., patients without AVN who have comparable distributions for four common parameters used in subject selection: gender, year of birth (age, treatment status, and splenectomy status. Matching resulted in odds ratios of approximately 1.00, indicating no bias. Conclusions We demonstrated bias in case-control selection in subjects from a prototype rare disease registry and used case-control matching to minimize this bias. Therefore, this approach appears useful to study cohorts of heterogeneous patients in rare disease registries.
Pavuluri, Pratyusha; Vadakedath, Sabitha; Gundu, Rajkumar; Uppulety, Sushmitha
Krabbe disease is a rare (one in 100,000 births) autosomal recessive condition, usually noticed among children. It causes sphingolipidosis (dysfunctional metabolism of sphingolipids) and leads to fatal degenerative changes affecting the myelin sheath of the nervous system. We report a case of a six-year-old male child who presented with symptoms of muscle spasticity and irritability. Diagnosis of this disease can only be made with clinical suspicion. Laboratory diagnosis includes brain magnetic resonance imaging (MRI), magnetic resonance (MR) spectroscopy, biochemical analysis of cerebrospinal fluid, and genetic analysis for detecting mutation in genes coding for galactosyl cerebroside (GALC). We report a case of late infantile Krabbe disease.
Kamil Hakan Kaya
Full Text Available Velopharyngeal insufficiency (VPI, in which the velopharyngeal port does not close during speech, is an important condition that reduces the quality of life in affected patients. Behçet’s disease (BD is a systemic autoimmune vasculitis with effects on many organs and systems in the body. Patients with BD may have otorhinolaryngological symptoms as part of its multi-system disease involvement. In rare cases, autoimmune diseases have been linked to VPI. Here we report the first case of BD diagnosed in a patient with VPI.
Knight, Stacey; Abo, Ryan P; Abel, Haley J; Neklason, Deborah W; Tuohy, Therese M; Burt, Randall W; Thomas, Alun; Camp, Nicola J
Shared genomic segment (SGS) analysis uses dense single nucleotide polymorphism genotyping in high-risk (HR) pedigrees to identify regions of sharing between cases. Here, we illustrate the power of SGS to identify dominant rare risk variants. Using simulated pedigrees, we consider 12 disease models based on disease prevalence, minor allele frequency and penetrance to represent disease loci that explain 0.2-99.8% of total disease risk. Pedigrees were required to contain ≥ 15 meioses between all cases and to be HR based on significant excess of disease (P power for a single pedigree ranged widely. Nonetheless, fewer than 10 pedigrees were sufficient for excellent power in the majority of models. Power increased with the risk attributable to the disease locus, penetrance and the excess of disease in the pedigree. Sharing allowing for one sporadic case was uniformly more powerful than sharing using all cases. Furthermore, an SGS analysis using a large attenuated familial adenomatous polyposis pedigree identified a 1.96 Mb region containing the known causal APC gene with genome-wide significance. SGS is a powerful method for detecting rare variants and a valuable complement to genome-wide association studies and linkage analysis.
Narayana Gowda, BS; Mohan Kumar, J; Basim, Praveen Kumar
Introduction: Hirayama's disease is a rare benign disorder, also referred to as monomelic amyotrophy (MMA), Juvenile non progressive amyotrophy, Sobue disease. It is a focal, lower motor neuron type of disease. Mainly young males in their second and third decades of age are most commonly affected. It is seen most commonly in Asian countries like India and Japan. In majority of people cause of this disease is unknown. MRI of cervical spine in flexion will reveal the cardinal features of Hirayama disease. Case Report: A 22 year gentleman came with a history of insidious onset of weakness in both the hands begenning with left side followed by right of 4 years duration. On examination he had clawing of both hands with wasting of forearm muscles. Lower limbs had no abnormality with normal deep tendon reflexes. MRI showed thinning of cord from C4 to C7 level suggestive of cord atrophy. Based on these features a diagnosis of focal amyotrophy was made. A cervical collar was prescribed and patient is under regular follow up. Conclusion: Hirayama disease is a rare self-limiting disease. Early diagnosis is necessary as the use of a simple cervical collar which will prevent neck flexion, has been shown to stop the progression PMID:27298910
Lin, Jin-Ding; Lin, Lan-Ping; Hung, Wen-Jiu
This paper aims to describe a general demographic picture of patients with rare diseases in Taiwan and particularly focuses on the prevalence of rare diseases over time, age and gender distributions. We analyzed data mainly from the national disability registry from 2002 to 2011 in Taiwan, Republic of China. The results showed that the number of…
Tannenbaum, Rebecca; Penney, Samantha; Lupski, James R.; Hopkin, Robert J.; Sutton, V. Reid
Rare genetic disorders can go undiagnosed for years as the entire spectrum of phenotypic variation is not well characterized given the reduced number of patients reported in the literature and the low frequency at which these occur. Moreover, the current paradigm for clinical diagnostics defines disease diagnosis by a specified spectrum of phenotypic findings; when such parameters are either missing, or other findings not usually observed are seen, the phenotype driven approach to diagnosis may result in a specific etiological diagnosis not even being considered within the differential diagnosis. The novel implementation of genomic sequencing approaches to investigate rare genetic disorders is allowing not only the discovery of new genes, but also the phenotypic expansion of known Mendelian genetic disorders. Here we report the detailed clinical assessment of a patient with a rare genetic disorder with undefined molecular diagnosis. We applied whole-exome sequencing to this patient and unaffected parents in order to identify the molecular cause of her disorder. We identified compound heterozygous mutations in the CTSA gene, responsible for causing galactosialidosis; the molecular diagnosis was further confirmed by biochemical studies. This report expands on the clinical spectrum of this rare lysosomal disorder and exemplifies how genomic approaches are further elucidating the characterization and understanding of genetic diseases. PMID:24769197
Helm, Benjamin M
The main goal of the constructivist meaning-making framework is to encourage grief adaptation through the search for meaning in loss. Strategies to help patients construct meaning from their experiences may lead to positive adaptation. This strategy has been used in contemporary grief counseling, but it may also be beneficial in the genetic counseling scenario. The diagnosis of a rare genetic disorder often has considerable psychosocial impact as patients and families describe feelings of isolation and hopelessness. Negative experiences with healthcare providers often reinforce these feelings. Genetic counselors continue to provide education and psychosocial support to patients and families with rare genetic disorders, and meaning-making strategies may provide a framework for which to help patients and families adapt to these challenging diagnoses. In this paper I explore the background of meaning-making counseling strategy and describe an experience in which it was used for counseling a family with a child with Mowat-Wilson syndrome. I show how a meaning-making framework can help families explore and construct meaning from their experiences and encourage positive adaptation. I also address the possible limitations of this strategy and the need to share additional experiences with this counseling framework. Meaning-making can be another tool for genetic counselors to help guide families in their grief and adaptation to rare disease diagnoses. I also describe qualities and aspects of counseling through the lens of meaning-making and stress the importance of addressing psychosocial dimensions of rare disease diagnoses.
Ortega Calvo, Manuel; Gómez-Chaparro Moreno, José Luis; González-Meneses López, Antonio; Guillén Enríquez, Javier; Varo Baena, Antonio; Fernández de la Mota, Elvira
Rare diseases are a real public health problem for hospitals and also for primary care. We describe some metaphor-based diagnosis procedures, such as: "When you hear hoof beats don't always think horses, sometimes they could be zebras", or that one about the antiquarian who recognised a museum masterpiece while walking in the Rastro (Madrid). The "lightning diagnoses" by Skoda are an important historic record. T. Greenhalgh has tried to cover the gap between evidence based medicine and the intuitive diagnosis. We point out some clinical epidemiology rules in order to improve their early detection by family practitioners and paediatricians. In our opinion, the training in the diagnosis of rare diseases has to be different for primary care level and for hospital doctors. Concept maps are useful for diagnosis in primary care clinics.
Full Text Available We are reporting a rare case of severe hemolytic disease of newborn (HDN with Bombay phenotype mother. A retrospective study of a case with severe haemolytic disease of newborn with Bombay phenotype mother was done. Blood grouping, antibody screening, and lectin study was done on the blood sample of the baby and mother to confirm the diagnosis. Hematological and biochemical parameters were obtained from the hospital laboratory information system for the analysis. Blood group of the baby was A positive, direct antiglobulin test was negative. Blood group of the mother was confirmed to be Bombay phenotype, Hematological parameters showed all the signs of ongoing hemolysis and the bilirubin level was in the zone of exchange transfusion. Due to the unavailability of this rare phenotype blood unit, baby was managed conservatively. Anticipating the fetal anemia and HDN with mothers having Bombay phenotype and prior notification to the transfusion services will be of great help in optimizing the neonatal care and outcome.
Shastry, Shamee; Lewis, Leslie E; Bhat, Sudha S
We are reporting a rare case of severe hemolytic disease of newborn (HDN) with Bombay phenotype mother. A retrospective study of a case with severe haemolytic disease of newborn with Bombay phenotype mother was done. Blood grouping, antibody screening, and lectin study was done on the blood sample of the baby and mother to confirm the diagnosis. Hematological and biochemical parameters were obtained from the hospital laboratory information system for the analysis. Blood group of the baby was A positive, direct antiglobulin test was negative. Blood group of the mother was confirmed to be Bombay phenotype, Hematological parameters showed all the signs of ongoing hemolysis and the bilirubin level was in the zone of exchange transfusion. Due to the unavailability of this rare phenotype blood unit, baby was managed conservatively. Anticipating the fetal anemia and HDN with mothers having Bombay phenotype and prior notification to the transfusion services will be of great help in optimizing the neonatal care and outcome.
This article analyses the specific rights of patients with rare diseases from a dual perspective. On the one hand, they concern a new generation of patients' rights that arise once the consolidation of basic rights has occurred, fundamentally after the application of Law 41/2002 (on Regulating Patient Autonomy and Rights and Obligations in the Field of Health Documentation and Information) and its development by the autonomous communities. On the other hand, the fundamental question raises a serious issue related to these patients, which involves the principles of equality, equity, non-discrimination and solidarity. This is aimed at promoting legislative measures to protect patients' equality of access to health and social services, with the ultimate aim of improving their quality of life. The author has given special relevance in his study to the treatment of rare diseases that are genetic in origin, and to the importance of adequate genetic counseling.
Kyselová, Kateřina; Viszlayová, Daša; Morimoto, Takaaki; Roubec, Martin; Školoudík, David; Petrovičová, Andrea; Juskanič, Dominik; Strauss, Jozef; Halaj, Marián; Kurray, Peter; Hranai, Marián; Harada, Kouji H.; Inoue, Sumiko; Yoshida, Yukako; Habu, Toshiyuki; Herzig, Roman; Youssefian, Shohab; Koizumi, Akio
RNF213/Mysterin has been identified as a susceptibility gene for moyamoya disease, a cerebrovascular disease characterized by occlusive lesions in the circle of Willis. The p.R4810K (rs112735431) variant is a founder polymorphism that is strongly associated with moyamoya disease in East Asia. Many non-p.R4810K rare variants of RNF213 have been identified in white moyamoya disease patients, although the ethnic mutations have not been investigated in this population. In the present study, we screened for RNF213 variants in 19 Slovakian and Czech moyamoya disease patients. A total of 69 RNF213 coding exons were directly sequenced in 18 probands and one relative who suffered from moyamoya disease in Slovakia and the Czech Republic. We previously reported one proband harboring RNF213 p.D4013N. Results from the present study identified four rare variants other than p.D4013N (p.R4019C, p.E4042K, p.V4146A, and p.W4677L) in four of the patients. P.V4146A was determined to be a novel de novo mutation, and p.R4019C and p.E4042K were identified as double mutations inherited on the same allele. P.W4677L, found in two moyamoya disease patients and an unaffected subject in the same pedigree, was a rare single nucleotide polymorphism. Functional analysis showed that RNF213 p.D4013N, p.R4019C and p.V4146A-transfected human umbilical vein endothelial cells displayed significant lowered migration, and RNF213 p.V4146A significantly reduced tube formation, indicating that these are disease-causing mutations. Results from the present study identified RNF213 rare variants in 22.2% (4/18 probands) of Slovakian and Czech moyamoya disease patients, confirming that RNF213 may also be a major causative gene in a relative large population of white patients. PMID:27736983
Bashaw, E D
Orphan drugs or drugs for rare diseases represents a particular regulatory conundrum. There is a desperate need for effective therapies for these patients, who have been historically underserved by the drug development community. However, there is also a need to make sure these therapies are both safe and effective. In response, the US Food and Drug Administration (FDA) has evolved new approaches to facilitate drug development in this area.
Botelho, Luciane Francisca Fernandes; Enokihara, Milvia Maria Simões e Silva; Enokihara, Mauro Yoshiaki
Necrolytic acral erythema is a rare skin disease associated with hepatitis C virus infection. We report a case of a 31-year-old woman with hepatitis C virus infection and decreased zinc serum level. Physical examination revealed scaly, lichenified plaques, well-demarcated with an erythematous peripheral rim located on the lower limbs. After blood transfusion and oral zinc supplementation the patient presented an improvement of lesions. PMID:27828642
Ayse Filiz Avsar
Full Text Available Fibroepithelial polyps (FEPs are rarely seen lesions of the lower female genital tract with polypoid proliferations of stroma. These tumors usually present in the vulvovaginal region of the reproductive aged women. In this presentation, we report a case of a psoriatic woman who developed unusual multiple polypoid lesions approximately 15 cm in size arising from both left and right labia minora and unique connection of FEPs with psoriasis disease.
Banshi Lal Kumawat
Full Text Available Sporadic Creutzfeldt-Jakob disease (sCJD can have varied clinical presentation depending upon the genotype at codon 129. The common presenting clinical features of sCJD are rapid onset cognitive impairment, ataxia, psychosis and visual signs (field defects, distortion, cortical blindness. Alien limb sign was first described in patients with corpus callosal tumors and later with other neurodegenerative conditions like corticobasal degeneration. Alien hand complaints as the presenting feature of sCJD has been described in literature, but simultaneous alien hand and leg has been rarely described as presenting feature of sCJD. We describe here a case of a 55-year-old man who presented with progressive left alien hand and leg as the sole clinical manifestation of probable sCJD.
Kumawat, Banshi Lal; Sharma, Chandra Mohan; Nath, Kunal; Acharya, Mihir; Khandelwal, Dinesh; Jain, Deepak
Sporadic Creutzfeldt-Jakob disease (sCJD) can have varied clinical presentation depending upon the genotype at codon 129. The common presenting clinical features of sCJD are rapid onset cognitive impairment, ataxia, psychosis and visual signs (field defects, distortion, cortical blindness). Alien limb sign was first described in patients with corpus callosal tumors and later with other neurodegenerative conditions like corticobasal degeneration. Alien hand complaints as the presenting feature of sCJD has been described in literature, but simultaneous alien hand and leg has been rarely described as presenting feature of sCJD. We describe here a case of a 55-year-old man who presented with progressive left alien hand and leg as the sole clinical manifestation of probable sCJD. PMID:25745324
Xiao-Xiong Xin; Liang Zhao; Xiao-Dong Guan; Lu-Wen Shi
Background:China has not established social security system for rare diseases.Rare diseases could easily impoverish patients and their families.Little research has studied the equity and accessibility of health services for patients with rare diseases in China.This study aimed to explore the factors that influence health expenditure of rare diseases and evaluate its equity.Methods:Questionnaire survey about living conditions and cost burden of patients with rare diseases was conducted.Individual and family information,health expenditure and reimbursement in 2014 of 982 patients were collected.The impact of medical insurance,individual sociodemographic characteristics,family characteristics,and healthcare need on total and out-of-pocket (OOP) health expenditures was analyzed through the generalized linear model.Equity of health expenditure was evaluated by both concentration index and Lorenz curve.Results:Of all the surveyed patients,11.41％ had no medical insurance and 92.10％ spent money to seek medical treatment in 2014.It was suggested female (P =0.048),over 50 years of age (P =0.062),high-income group (P =0.021),hospitalization (P =0.000),and reimbursement ratio (RR) (P =0.000) were positively correlated with total health expenditure.Diseases not needing long-term treatment (P =0.000) was negatively correlated with total health expenditure.Over 50 years of age (P =0.065),high-income group (P =0.018),hospitalization (P =0.000) and having Urban Employee Basic Medical Insurance (UEBMI) (P =0.022) were positively correlated with OOP health expenditure.Patient or the head of the household having received higher education (P =0.044 and P =0.081) and reimbursement ratio (P =0.078) were negatively correlated with OOP health expenditure.The equity evaluation found concentration indexes of health expenditure before and after reimbursement were 0.0550 and 0.0539,respectively.Conclusions:OOP health expenditure of patients with UEBMI was significantly more than that of
Pinnapureddy, Ashish R; Stayner, Cherie; McEwan, John; Baddeley, Olivia; Forman, John; Eccles, Michael R
Animals that accurately model human disease are invaluable in medical research, allowing a critical understanding of disease mechanisms, and the opportunity to evaluate the effect of therapeutic compounds in pre-clinical studies. Many types of animal models are used world-wide, with the most common being small laboratory animals, such as mice. However, rodents often do not faithfully replicate human disease, despite their predominant use in research. This discordancy is due in part to physiological differences, such as body size and longevity. In contrast, large animal models, including sheep, provide an alternative to mice for biomedical research due to their greater physiological parallels with humans. Completion of the full genome sequences of many species, and the advent of Next Generation Sequencing (NGS) technologies, means it is now feasible to screen large populations of domesticated animals for genetic variants that resemble human genetic diseases, and generate models that more accurately model rare human pathologies. In this review, we discuss the notion of using sheep as large animal models, and their advantages in modelling human genetic disease. We exemplify several existing naturally occurring ovine variants in genes that are orthologous to human disease genes, such as the Cln6 sheep model for Batten disease. These, and other sheep models, have contributed significantly to our understanding of the relevant human disease process, in addition to providing opportunities to trial new therapies in animals with similar body and organ size to humans. Therefore sheep are a significant species with respect to the modelling of rare genetic human disease, which we summarize in this review.
Godswill, Okwuonu Chimezie; Odigie, Ojeh-Oziegbe
Coexistence of Addison's disease and systemic lupus erythematosus (SLE) is a rare occurrence with only few reported cases in the literature. We describe a 29-year-old woman who presented to us with clinical features of acute Addisonian crisis and SLE. Laboratory investigations were confirmatory of Addison's disease in a background of SLE. The patient made remarkable improvement on administration of steroids as replacement therapy for adrenal insufficiency and treatment of SLE. Clinicians need to have a high-index of suspicion of this possible coexistence in order to avoid the associated deleterious hemodynamic and metabolic consequences.
Dragojlovic, Nick; Lynd, Larry D
In this article, we present descriptive data on 125 crowdfunding campaigns aimed at financing research in oncology (including basic research, drug discovery, and clinical trials). We also describe five campaigns that have succeeded in raising substantial funds to support the development of treatments for ultrarare diseases. The data suggest that crowdfunding is a viable approach to supporting early proof-of-concept research that could allow researchers in oncology and rare diseases to succeed in traditional grant competitions or to attract private investment. The data also suggest that such an approach could become a valuable additional source of funding for early-stage innovators in the drug development arena.
Full Text Available Rare genetic or inherited forms of diabetes can mimic immune mediated type 1 diabetes. Early age of onset and associated features help to differentiate these diseases from type 1 diabetes. Wolfram syndrome, an inherited neuro degenerative disorder, presents as insulin dependent diabetes mellitus, diabetes insipidus, optic atrophy and deafness. But less well described features like psychiatric manifestations can be the presentation of this disease. We present such a case. Wolfram syndrome should be considered as a differential diagnosis in insulin dependent diabetic children who present with neuropsychiatric problems.
Gan, Earn H; MacArthur, Katie; Mitchell, Anna L; Pearce, Simon H S
Background Autoimmune Addison's disease (AAD) is a rare condition with a complex genetic basis. A panel of rare and functionally defective genetic variants in the sialic acid acetylesterase (SIAE) gene has recently been implicated in several common autoimmune conditions. We performed a case–control study to determine whether these rare variants are associated with a rarer condition, AAD. Method We analysed nine SIAE gene variants (W48X, M89V, C196F, C226G, R230W, T312M, Y349C, F404S and R479C) in a United Kingdom cohort of 378 AAD subjects and 387 healthy controls. All samples were genotyped using Sequenom iPlex chemistry to characterise primer extension products. Results A heterozygous rare allele at codon 312 (312*M) was found in one AAD patient (0.13%) but was not detected in the healthy controls. The commoner, functionally recessive variant at codon 89 (89*V) was found to be homozygous in two AAD patients but was only found in the heterozygous state in controls. Taking into account all nine alleles examined, 4/378 (1.06%) AAD patients and 1/387 (0.25%) healthy controls carried the defective SIAE alleles, with a calculated odds ratio of 4.13 (95% CI 0.44–97.45, two-tailed P value 0.212, NS). Conclusion We demonstrated the presence of 89*V homozygotes and the 312*M rare allele in the AAD cohort, but overall, our analysis does not support a role for rare variants in SIAE in the pathogenesis of AAD. However, the relatively small collection of AAD patients limits the power to exclude a small effect. PMID:23011869
Lantos, John D.
Public policy surrounding newborn screening is in flux. New technology allows more screening for more diseases at lower cost. Traditional criteria for target diseases have been criticized by leading health policymakers. The example of newborn screening for Krabbe disease highlights many of the dilemmas associated with population-based screening…
Iizuka, Toshiaki; Uchida, Gyo
In many medical care markets with limited profit potential, firms often have little incentive to innovate. These include the market for rare diseases, "neglected" tropical diseases, and personalized medicine. Governments and not-for-profit organizations promote innovation in such markets but empirical evidence on the policy effect is limited. We study this issue by analyzing the impact of a demand-side policy in Japan, which reduces the cost sharing of patients with some rare and intractable diseases and attempts to establish and promote the treatment of those diseases. Using clinical trials data taken from public registries, we identify the effect of the policy using a difference-in-difference approach. We find that the demand-side policy increased firms' incentive to innovate: firm-sponsored clinical trials increased 181% (0.16 per disease per year) when covered by the policy. This result indicates that the demand-side policy can be an important part of innovation policies in markets with limited profit potential. Copyright © 2017 Elsevier B.V. All rights reserved.
Kyaw, Htoo; Grillo, Michael; Lin, Aung Naing; Kapp, David A
Madelung's disease is a neglected metabolic disease characterised by generalised multiple fatty tissue deposits. A 64-year-old Caucasian woman presented with generalised weakness and symptomatic hypoglycaemia with altered mental status. Physical examination showed very distinct physical characteristics with multiple lumps distributed over the upper body. Her neurological symptoms were solved by giving intravenous glucose and optimisation of medical treatment. Even though she had unique characteristics of Madelung's disease, many physicians, on several occasions, failed to recognise her 'hidden diagnosis'. This diagnostic uncertainty was able to be solved by searching the Internet for similar clinical features and images. This case demonstrates characteristics and unique features of a rare disease that can be seen in a female patient even though it is mostly found in males.
Kakkis, Emil D; O'Donovan, Mary; Cox, Gerald; Hayes, Mark; Goodsaid, Federico; Tandon, P K; Furlong, Pat; Boynton, Susan; Bozic, Mladen; Orfali, May; Thornton, Mark
For rare serious and life-threatening disorders, there is a tremendous challenge of transforming scientific discoveries into new drug treatments. This challenge has been recognized by all stakeholders who endorse the need for flexibility in the regulatory review process for novel therapeutics to treat rare diseases. In the United States, the best expression of this flexibility was the creation of the Accelerated Approval (AA) pathway. The AA pathway is critically important for the development of treatments for diseases with high unmet medical need and has been used extensively for drugs used to treat cancer and infectious diseases like HIV.In 2012, the AA provisions were amended to enhance the application of the AA pathway to expedite the development of drugs for rare disorders under the Food and Drug Administration Safety and Innovation Act (FDASIA). FDASIA, among many provisions, requires the development of a more relevant FDA guidance on the types of evidence that may be acceptable in support of using a novel surrogate endpoint. The application of AA to rare diseases requires more predictability to drive greater access to appropriate use of AA for more rare disease treatments that might not be developed otherwise.This white paper proposes a scientific framework for assessing biomarker endpoints to enhance the development of novel therapeutics for rare and devastating diseases currently without adequate treatment and is based on the opinions of experts in drug development and rare disease patient groups. Specific recommendations include: 1) Establishing regulatory rationale for increased AA access in rare disease programs; 2) Implementing a Biomarker Qualification Request Process to provide the opportunity for an early determination of biomarker acceptance; and 3) A proposed scientific framework for qualifying biomarkers as primary endpoints. The paper's final section highlights case studies of successful examples that have incorporated biomarker endpoints into
Ankur Nandan Varshney
Full Text Available Extranodal NK/T-cell Lymphoma of nasal type is a rare and comparatively a new entry among group of Non-Hodgkin lymphomas. The disease is characterized by a clinically aggressive course with involvement of upper aero-digestive tract and classical immune-phenotyping with CD2, CD3 and CD56 positivity. Being a rare entity, treatment entities are yet not formulated in guidelines. We hereby report a case of extranodal NK/T-cell lymphoma with predominant T cell markers who was initially treated with CHOP regime of non-Hodgkin lymphoma and later successfully treated with SMILE regime.
Maharshi H Patel
Full Text Available Sinus histiocytosis with massive lymphadenopathy (SHML or Rosai-Dorfman disease is a non-neoplastic condition which typically presents as massive, bilateral cervical lymphadenopathy and can involve multiple extranodal organ systems such as skin, eyes, and upper respiratory tract in about 28% cases. Bone lesions in association with nodal disease are seen in less than 10% cases. Isolated bone involvement as the only manifestation of SHML is extremely rare, with less than 50 cases reported in the literature. We report a very uncommon case of Rosai-Dorfman disease with isolated multifocal osseous involvement as the only presenting feature, involving about 10 different sites with no lymphadenopathy or other organ system involvement.
Karaca, Ender; Harel, Tamar; Pehlivan, Davut; Jhangiani, Shalini N.; Gambin, Tomasz; Akdemir, Zeynep Coban; Gonzaga-Jauregui, Claudia; Erdin, Serkan; Bayram, Yavuz; Campbell, Ian M.; Hunter, Jill V.; Atik, Mehmed M.; Van Esch, Hilde; Yuan, Bo; Wiszniewski, Wojciech; Isikay, Sedat; Yesil, Gozde; Yuregir, Ozge O.; Bozdogan, Sevcan Tug; Aslan, Huseyin; Aydin, Hatip; Tos, Tulay; Aksoy, Ayse; De Vivo, Darryl C.; Jain, Preti; Geckinli, B. Bilge; Sezer, Ozlem; Gul, Davut; Durmaz, Burak; Cogulu, Ozgur; Ozkinay, Ferda; Topcu, Vehap; Candan, Sukru; Cebi, Alper Han; Ikbal, Mevlit; Gulec, Elif Yilmaz; Gezdirici, Alper; Koparir, Erkan; Ekici, Fatma; Coskun, Salih; Cicek, Salih; Karaer, Kadri; Koparir, Asuman; Duz, Mehmet Bugrahan; Kirat, Emre; Fenercioglu, Elif; Ulucan, Hakan; Seven, Mehmet; Guran, Tulay; Elcioglu, Nursel; Yildirim, Mahmut Selman; Aktas, Dilek; Alikaşifoğlu, Mehmet; Ture, Mehmet; Yakut, Tahsin; Overton, John D.; Yuksel, Adnan; Ozen, Mustafa; Muzny, Donna M.; Adams, David R.; Boerwinkle, Eric; Chung, Wendy K.; Gibbs, Richard A.; Lupski, James R
Development of the human nervous system involves complex interactions between fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate genes, and CNVs in 10 families, with an overall potential molecular cause identified in >85% of families studied. Among the candidate genes identified, we found PRUNE, VARS, and DHX37 in multiple families, and homozygous loss of function variants in AGBL2, SLC18A2, SMARCA1, UBQLN1, and CPLX1. Neuroimaging and in silico analysis of functional and expression proximity between candidate and known disease genes allowed for further understanding of genetic networks underlying specific types of brain malformations. PMID:26539891
Osmanagic, Azra; Emamifar, Amir; Christian Bang, Jacob;
BACKGROUND Pott's disease (PD) or spinal tuberculosis is a rare condition which accounts for less than 1% of total tuberculosis (TB) cases. The incidence of PD has recently increased in Europe and the United States, mainly due to immigration; however, it is still a rare diagnosis in Scandinavian...... was suggestive of PD. Polymerase chain reaction (PCR) of the patient's gastric fluid was positive for Mycobacterium tuberculosis (MT). Based on MRI and PCR findings, standard treatment for TB was initiated. Results of the spine biopsy and culture showed colonies of MT and confirmed the diagnosis afterwards. Due...... to the instability of the spine and severe and continuous pain, spine-stabilizing surgery was performed. Her TB was cured after nine months of treatment. CONCLUSIONS PD is an important differential diagnosis of malignancy that should be diagnosed instantly. History of exposure to TB and classic radiologic finding...
Çakan, Mustafa; Gemici, Hakan; Aktay-Ayaz, Nuray; Keskindemirci, Gonca; Bornaun, Helen; İkizoğlu, Tarkan; Çeliker, Alpay
Kawasaki disease is an acute systemic vasculitis that occurs most commonly in young children. It affects medium-sized muscular arteries and the coronary arteries are the predominant site of involvement. Morbidity and mortality is generally due to coronary artery aneurysms that develop during the chronic phase. Although it is well known that Kawasaki disease can cause myocarditis, tachycardia and heart failure during acute stage, Kawasaki disease shock syndrome has been recently described. It is characterized by hypotension, signs and symptoms of poor perfusion and a shock-like state. Herein we describe two cases of Kawasaki disease shock syndrome that were treated in the pediatric intensive care unit and followed a course without morbidity or mortality.
Epidemiologists often use ratio-type indices (rate ratio, risk ratio and odds ratio) to quantify the association between exposure and disease. By comparison, less attention has been paid to effect measures on a difference scale (excess rate or excess risk). The excess relative risk (ERR) used primarily by radiation epidemiologists is of peculiar interest here, in that it involves both difference and ratio operations. The ERR index (but not the difference-type indices) is estimable in case-control studies. Using the theory of sufficient component cause model, the author shows that when there is no mechanistic interaction (no synergism in the sufficient cause sense) between the exposure under study and the stratifying variable, the ERR index (but not the ratio-type indices) in a rare-disease case-control setting should remain constant across strata and can therefore be regarded as a common effect parameter. By exploiting this homogeneity property, the related attributable fraction indices can also be estimated with greater precision. The author demonstrates the methodology (SAS codes provided) using a case-control dataset, and shows that ERR preserves the logical properties of the ratio-type indices. In light of the many desirable properties of the ERR index, the author advocates its use as an effect measure in case-control studies of rare diseases.
Full Text Available Epidemiologists often use ratio-type indices (rate ratio, risk ratio and odds ratio to quantify the association between exposure and disease. By comparison, less attention has been paid to effect measures on a difference scale (excess rate or excess risk. The excess relative risk (ERR used primarily by radiation epidemiologists is of peculiar interest here, in that it involves both difference and ratio operations. The ERR index (but not the difference-type indices is estimable in case-control studies. Using the theory of sufficient component cause model, the author shows that when there is no mechanistic interaction (no synergism in the sufficient cause sense between the exposure under study and the stratifying variable, the ERR index (but not the ratio-type indices in a rare-disease case-control setting should remain constant across strata and can therefore be regarded as a common effect parameter. By exploiting this homogeneity property, the related attributable fraction indices can also be estimated with greater precision. The author demonstrates the methodology (SAS codes provided using a case-control dataset, and shows that ERR preserves the logical properties of the ratio-type indices. In light of the many desirable properties of the ERR index, the author advocates its use as an effect measure in case-control studies of rare diseases.
Ayoglu, Burcu; Chaouch, Amina; Lochmüller, Hanns; Politano, Luisa; Bertini, Enrico; Spitali, Pietro; Hiller, Monika; Niks, Eric H; Gualandi, Francesca; Pontén, Fredrik; Bushby, Kate; Aartsma-Rus, Annemieke; Schwartz, Elena; Le Priol, Yannick; Straub, Volker; Uhlén, Mathias; Cirak, Sebahattin; 't Hoen, Peter A C; Muntoni, Francesco; Ferlini, Alessandra; Schwenk, Jochen M; Nilsson, Peter; Al-Khalili Szigyarto, Cristina
Despite the recent progress in the broad-scaled analysis of proteins in body fluids, there is still a lack in protein profiling approaches for biomarkers of rare diseases. Scarcity of samples is the main obstacle hindering attempts to apply discovery driven protein profiling in rare diseases. We addressed this challenge by combining samples collected within the BIO-NMD consortium from four geographically dispersed clinical sites to identify protein markers associated with muscular dystrophy using an antibody bead array platform with 384 antibodies. Based on concordance in statistical significance and confirmatory results obtained from analysis of both serum and plasma, we identified eleven proteins associated with muscular dystrophy, among which four proteins were elevated in blood from muscular dystrophy patients: carbonic anhydrase III (CA3) and myosin light chain 3 (MYL3), both specifically expressed in slow-twitch muscle fibers and mitochondrial malate dehydrogenase 2 (MDH2) and electron transfer flavoprotein A (ETFA). Using age-matched sub-cohorts, 9 protein profiles correlating with disease progression and severity were identified, which hold promise for the development of new clinical tools for management of dystrophinopathies. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.
Storf, Holger; Schaaf, Jannik; Kadioglu, Dennis; Göbel, Jens; Wagner, Thomas O F; Ückert, Frank
Meager amounts of data stored locally, a small number of experts, and a broad spectrum of technological solutions incompatible with each other characterize the landscape of registries for rare diseases in Germany. Hence, the free software Open Source Registry for Rare Diseases (OSSE) was created to unify and streamline the process of establishing specific rare disease patient registries. The data to be collected is specified based on metadata descriptions within the registry framework's so-called metadata repository (MDR), which was developed according to the ISO/IEC 11179 standard. The use of a central MDR allows for sharing the same data elements across any number of registries, thus providing a technical prerequisite for making data comparable and mergeable between registries and promoting interoperability.With OSSE, the foundation is laid to operate linked patient registries while respecting strong data protection regulations. Using the federated search feature, data for clinical studies can be identified across registries. Data integrity, however, remains intact since no actual data leaves the premises without the owner's consent. Additionally, registry solutions other than OSSE can participate via the OSSE bridgehead, which acts as a translator between OSSE registry networks and non-OSSE registries. The pseudonymization service Mainzelliste adds further data protection.Currently, more than 10 installations are under construction in clinical environments (including university hospitals in Frankfurt, Hamburg, Freiburg and Münster). The feedback given by the users will influence further development of OSSE. As an example, the installation process of the registry for undiagnosed patients at University Hospital Frankfurt is described in more detail.
Bryan, Jennifer L; Lu, Qian
This study implemented and evaluated the effectiveness of an expressive writing intervention among patients with Stargardt's disease, a rare disease due to macular degeneration. Participants were randomly assigned to either an expressive writing intervention or a neutral writing condition. Participants completed measures at three time points: baseline, 3 weeks, and 6 weeks post-intervention. Psychological health outcomes improved at the 3-week follow-up for the intervention condition compared to control. Self-reported physical health improved at the 6-week follow-up in the intervention condition compared to control. These results suggest that expressive writing may be an effective, practical, and low-cost intervention for those with Stargardt's disease.
Full Text Available Rare diseases by definition do not occur often and it is difficult to provide palliative care for those affected due to the lack of information and treatment for those rare diseases. The families of those with rare diseases bear a heavy burden and have a harder time than even the families of disabled people. This research’s goal is to provide the families of those with rare diseases with information on how to provide care for their family members. The study uses the qualitative research method of semi-structured interview. We interviewed 10 rare disease children and adolescents’ primary caregivers. The results of the study indicated that if no one suffers from the rare diseases in their family, primary caregivers are not aware of the rare disease information. After their initial diagnosis, the caregivers will want to know how to best care for their family member, from how best to provide supportive care to providing physical therapy, in order to improve their quality of life and prognosis. When they discover their child’s disease is incurable, primary caregivers need information about social welfare and their child’s future. The main source of medical care information is provided by hospitals and patient-support organizations. Regarding information behavior, primary caregivers employ the information which they obtain and they either check the information they obtain with a professional authority, multiple sources, or compare it with patient experience to validate if the information is accurate or not. Finally, primary caregivers are glad to share what they find with other families that have children with a rare disease. They may use different ways of sharing information such as the Internet or face to face. [Article content in Chinese
Zuraw, Bruce L; Christiansen, Sandra C
Rare diseases, including hereditary angioedema, present a unique set of challenges for clinicians and investigators. The most successful way to negotiate these difficulties has been to develop collaborative efforts among physicians and with patient advocacy organizations and pharmaceutical companies. The US Hereditary Angioedema Association is a large nonprofit patient advocacy organization that has been the catalyst for these types of collaborative arrangements involving hereditary angioedema. The dedication and unique structure of this patient advocacy organization has allowed it to make a substantial contribution to improving hereditary angioedema diagnosis and care. Published by Elsevier Inc.
Christopher A. Behr
Full Text Available Localized cystic disease of the kidney (LCDK is a rare condition found primarily in adults, with the total number of documented cases less than 75. Its incidence in the pediatric population is even more minuscule. It is a benign condition, but can be difficult to classify with certainty on imaging, often necessitating surgical excision to adequately rule out a malignancy. We present the case of a six-year-old child with a cystic mass of the kidney who underwent a radical nephroureterectomy, for which pathology showed LCDK. We then review the literature on the subject.
Full Text Available Dowling Degos disease is a rare, reticulate pigmentary disorder with variable phenotypic expression that manifests as hyperpigmented macules and reticulate pigmentary anomaly of the flexures. Many variants of this condition and its overlap with other reticulate pigmentary disorders have been reported in the literature. We present here two cases of DDD with follicular localization, both clinically and histologically. It was associated with ichthyosis vulgaris in one case. Follicular DDD is an uncommon variant of this evolving dermatosis. Our report supports the possible role for disordered follicular keratinisation in its pathogenesis.
Bala, Senduran; Clapham, Peter; Coates, Guy;
The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively...... phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single...... resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results....
Wilson's disease is a rare autosomal recessive disease characterised by the deposition of copper in the brain, liver; cornea, and other organs. The overload of copper inevitably leads to progressive liver and neurological dysfunction. Copper overload in patients with Wilson's disease is caused by impairment to the biliary route for excretion of dietary copper A combination of neurological, psychiatric and hepatic symptoms can make the diagnosis of Wilson's disease challenging. Most symptoms appear in the second and third decades of life. The disease affects between one in 30,000 and one in 100,000 individuals, and is fatal if left untreated. Five drugs are currently available to treat Wilson's disease: British Anti-Lewisite; D-penicillamine; trientine; zinc sulfate or acetate; and ammonium tetrathiomolybdate. Each drug can reduce copper levels and/or transform copper into a metabolically inert and unavailable form in the patient. The discovery and introduction of these five drugs owes more to the inspiration of a few dedicated physicians and agricultural scientists than to the resources of the pharmaceutical industry.
Full Text Available Rare diseases (RD are characterized by low prevalence and affect not more than five individuals per 10,000 in the European population; they are a large and heterogeneous group of disorders including more than 7,000 conditions and often involve all organs and tissues, with several clinical subtypes within the same disease. Very often information concerning either diagnosis and/or prognosis on many RD is insufficient. microRNAs are a class of small non-coding RNAs that regulate gene expression at the posttranscriptional level by either degrading or blocking translation of messenger RNA targets. Recently, microRNA expression patterns of body fluids underscored their potential as noninvasive biomarkers for various diseases. The role of microRNAs as potential biomarkers has become particularly attractive. The identification of disease-related microRNAs is essential for understanding the pathogenesis of diseases at the molecular level, and is critical for designing specific molecular tools for diagnosis, treatment and prevention. Computational analysis of microRNA-disease associations is an important complementary means for prioritizing microRNAs for further experimental examination. In this article, we explored the added value of miRs as biomarkers in a selected panel of RD hitting different tissues/systems at different life stages, but sharing the need of better biomarkers for diagnostic and prognostic purposes.
Sardi, S Pablo; Cheng, Seng H; Shihabuddin, Lamya S
Gaucher disease, the most common lysosomal storage disease, is caused by a recessively inherited deficiency in glucocerebrosidase and subsequent accumulation of toxic lipid substrates. Heterozygous mutations in the lysosomal glucocerebrosidase gene (GBA1) have recently been recognized as the highest genetic risk factor for the development of α-synuclein aggregation disorders ("synucleinopathies"), including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Despite the wealth of experimental, clinical and genetic evidence that supports the association between mutant genotypes and synucleinopathy risk, the precise mechanisms by which GBA1 mutations lead to PD and DLB remain unclear. Decreased glucocerebrosidase activity has been demonstrated to promote α-synuclein misprocessing. Furthermore, aberrant α-synuclein species have been reported to downregulate glucocerebrosidase activity, which further contributes to disease progression. In this review, we summarize the recent findings that highlight the complexity of this pathogenetic link and how several pathways that connect glucocerebrosidase insufficiency with α-synuclein misprocessing have emerged as potential therapeutic targets. From a translational perspective, we discuss how various therapeutic approaches to lysosomal dysfunction have been explored for the treatment of GBA1-related synucleinopathies, and potentially, for non-GBA1-associated neurodegenerative diseases. In summary, the link between GBA1 and synucleinopathies has become the paradigm of how the study of a rare lysosomal disease can transform the understanding of the etiopathology, and hopefully the treatment, of a more prevalent and multifactorial disorder.
Manjila, Sunil; Miller, Benjamin R; Rao-Frisch, Anitha; Otvos, Balint; Mitchell, Anna; Bambakidis, Nicholas C; De Georgia, Michael A
Moyamoya disease is a rare cerebrovascular anomaly involving the intracranial carotid arteries that can present clinically with either ischemic or hemorrhagic disease. Moyamoya syndrome, indistinguishable from moyamoya disease at presentation, is associated with multiple clinical conditions including neurofibromatosis type 1, autoimmune disease, prior radiation therapy, Down syndrome, and Turner syndrome. We present the first reported case of an adult patient with previously unrecognized mosaic Turner syndrome with acute subarachnoid and intracerebral hemorrhage as the initial manifestation of moyamoya syndrome. A 52-year-old woman was admitted with a subarachnoid hemorrhage with associated flame-shaped intracerebral hemorrhage in the left frontal lobe. Physical examination revealed short stature, pectus excavatum, small fingers, micrognathia, and mild facial dysmorphism. Cerebral angiography showed features consistent with bilateral moyamoya disease, aberrant intrathoracic vessels, and an unruptured 4-mm right superior hypophyseal aneurysm. Genetic analysis confirmed a diagnosis of mosaic Turner syndrome. Our case report is the first documented presentation of adult moyamoya syndrome with subarachnoid and intracerebral hemorrhage as the initial presentation of mosaic Turner syndrome. It illustrates the utility of genetic evaluation in patients with cerebrovascular disease and dysmorphism.
Alberto Acevedo Rehbein
Este artículo analiza las cláusulas de mejores esfuerzos (best efforts). En la primera parte, el autor analiza desde la óptica del common law cómo las cortes estadounidenses han definido y determinado el alcance de las cláusulas de mejores esfuerzos. Posteriormente, se hace un análisis comparativo frente al ordenamiento jurídico colombiano con el propósito de determinar la aplicación de este tipo de cláusulas en Colombia. La tesis central del artículo es que las cláusulas de mejores esfuerzos...
M. Salazar-Villanueva; A. Bautista Hernández; P.H. Hernández Tejeda; J.F Rivas Silva; J.A. Ascencio
Recientemente se ha iniciado el estudio del esfuerzo ideal en nanomateriales. En el caso de c umulos el esfuerzo ideal m aximo se calcula en el punto de inflexi on de la curva de energ a vs. deformaci on. En este trabajo extendemos lo realizado por Kitamura et al. , incluyendo la parte vibracional en el estudio del esfuerzo ideal para c umulos de Si 6 y Si 7 usando la Teor a del Funcional de la Densidad (DFT). Para el tratamiento de los t erminos de correlaci on e intercambio se cons...
Jamma, Shailaja; Rubio-Tapia, Alberto; Kelly, Ciaran P.; Murray, Joseph; Sheth, Sunil; Schuppan, Detlef; Dennis, Melinda; Leffler, Daniel A.
Background & Aims Celiac crisis is a life-threatening syndrome in which patients with celiac disease have profuse diarrhea and severe metabolic disturbances. Celiac crisis is rare among adults and not well documented. To improve awareness of this condition and to facilitate diagnosis, we reviewed cases of celiac crisis to identify presenting features, formulate diagnostic criteria, and develop treatment strategies. Methods Cases of biopsy-proven celiac disease were reviewed. Celiac crisis was defined as acute onset or rapid progression of gastrointestinal symptoms that could be attributed to celiac disease and required hospitalization and/or parenteral nutrition, along with signs or symptoms of dehydration or malnutrition. Results Twelve patients met preset criteria for celiac crisis; 11 developed celiac crisis before they were diagnosed with celiac disease. Eleven patients had increased titres of tTG and 1 had immunoglobulin A deficiency. Results of biopsy analyses of duodenum samples from all patients were consistent with a Marsh 3 score (33% with total villous atrophy). Patients presented with severe dehydration, renal dysfunction, and electrolyte disturbances. All patients required hospitalization and intravenous fluids, 6 required corticosteroids, and 5 required parenteral nutrition. All patients eventually had a full response to a gluten-free diet. Conclusion Celiac crisis has a high morbidity and, although rarely described, occurs in adults and often has a clear precipitating factor. Patients that present with severe unexplained diarrhea and malabsorption should be tested for celiac disease; treatment with systemic steroids or oral budesonide should be considered. Nutritional support is often required in the short term but most patients ultimately respond to gluten avoidance. PMID:20417725
Gopi C Khilnani
Full Text Available Idiopathic pulmonary hemosiderosis (IPH is a rare cause of recurrent diffuse alveolar hemorrhage (DAH with no specific treatment. Herein, we discuss a case of hemoptysis, who had IPH and other rare associations. A 19-year-old man presented with recurrent hemoptysis, generalized weakness and progressive dyspnea for 3 years. Earlier, he was diagnosed with anemia and was treated with blood transfusions and hematinics. On examination he had pallor, tachycardia and was underweight. Investigations revealed low level of hemoglobin (7.8 g/dl and iron deficiency. An electrocardiography (ECG showed sinus tachycardia, interventricular conduction delay and T-wave inversion. Echocardiography revealed dilated cardiomyopathy with left ventricular dysfunction. Computed tomography of the chest demonstrated bilateral diffuse ground glass opacity suggestive of pulmonary hemorrhage. Pulmonary function tests showed restrictive pattern with increased carbon monoxide diffusion. Bronchoalveolar lavage and transbronchial lung biopsy showed hemosiderin-laden macrophages. Patient could recall recurrent episodes of diarrhea in childhood. Serum antitissue transglutamase antibodies were raised (291.66 IU/ml, normal <30 IU/ml. Duodenal biopsy showed subtotal villous atrophy consistent with celiac disease. He was started on gluten-free diet, beta blockers and diuretics. After two years of treatment, he has been showing consistent improvement. Screening for CD is important in patients with IPH. Cardiomyopathy forms rare third association. All three show improvement with gluten-free diet.
Erping Long; Shuangjuan Xu; Zhenzhen Liu; Xiaohang Wu; Xiayin Zhang; Jinghui Wang; Wangting Li; Runzhong Liu; Zicong Chen; Kexin Chen; Tongyong Yu; Dongxuan Wu; Xutu Zhao; Jingjing Chen; Zhuoling Lin; Qianzhong Cao
.... This study aims to investigate the interrelationship and the effectiveness of potential factors of pediatric cataract, for the exploration of data mining strategy in the scenarios of rare diseases...
Full Text Available Translating a set of disease regions into insight about pathogenic mechanisms requires not only the ability to identify the key disease genes within them, but also the biological relationships among those key genes. Here we describe a statistical method, Gene Relationships Among Implicated Loci (GRAIL, that takes a list of disease regions and automatically assesses the degree of relatedness of implicated genes using 250,000 PubMed abstracts. We first evaluated GRAIL by assessing its ability to identify subsets of highly related genes in common pathways from validated lipid and height SNP associations from recent genome-wide studies. We then tested GRAIL, by assessing its ability to separate true disease regions from many false positive disease regions in two separate practical applications in human genetics. First, we took 74 nominally associated Crohn's disease SNPs and applied GRAIL to identify a subset of 13 SNPs with highly related genes. Of these, ten convincingly validated in follow-up genotyping; genotyping results for the remaining three were inconclusive. Next, we applied GRAIL to 165 rare deletion events seen in schizophrenia cases (less than one-third of which are contributing to disease risk. We demonstrate that GRAIL is able to identify a subset of 16 deletions containing highly related genes; many of these genes are expressed in the central nervous system and play a role in neuronal synapses. GRAIL offers a statistically robust approach to identifying functionally related genes from across multiple disease regions--that likely represent key disease pathways. An online version of this method is available for public use (http://www.broad.mit.edu/mpg/grail/.
Full Text Available Darier’s disease (DD is a rare acantholytic dyskeratotic autosomal dominant genodermatosis characterized by the presence of warty, brown papules and plaques affecting the seborrhoeic areas. Frequent bacterial, fungal and viral particularly herpes simplex virus (HSV infections complicate DD. Bell’s palsy is an acute onset, idiopathic facial paralysis resulting from a dysfunction anywhere along the peripheral part of the facial nerve. Reactivation of HSV is considered to be the main cause of Bell’s palsy. This case represents, to the best of our knowledge, the first case of DD presenting with Bell’s palsy. This case underlines the importance of recognizing HSV infection in DD.
Kontoghiorghe, Christina N; Andreou, Nicholas; Constantinou, Katerina; Kontoghiorghes, George J
According to global annual estimates hunger/malnutrition is the major cause of death (36 of 62 million). Cardiovascular diseases and cancer (5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis (10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countries was 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone (L1) for thalassaemia up to the stage of multicentre clinical trials. The
Full Text Available Creutzfeldt-Jakob disease (CJD is a rare, fatal neurodegenerative disease caused by an infectious protein called prion and is characterized by spongiform changes, neuronal loss, reactive astrocytic proliferation, and accumulation of pathologic cellular protein. Clinical presentation of CJD is characterized by rapidly progressive dementia, neurologic symptoms and visual impairment, and the development of akinetic mutism, which can mimic many neurological conditions. The diagnosis is based on clinical presentation, electroencephalogram, and typical cerebrospinal fluid and magnetic resonance imaging (MRI findings. Literature on the incidence and prevalence of CJD is lacking in South India. We report the case of a 57-year-old woman with progressive dementia and typical neurologic symptoms, myoclonic jerks, and MRI findings of CJD. This case highlights the need for a high index of suspicion to diagnose CJD.
Taillefer, Marguerite S; Tangarorang, Glendo L; Kuchel, George A; Menkes, Daniel L
We report an atypical presentation of sporadic Creutzfeldt-Jakob disease (CJD) in a 74-year-old woman that illustrates the difficulty in diagnosing this rare, but important, cause of rapidly progressive dementia. Despite well-established criteria, this diagnosis is often missed or substantially delayed (Table 1). In this case, a precipitous cognitive decline associated with a urinary tract infection initiallysuggested delirium. Although atypical CJD was considered as a cause when symptoms persisted, a definitive diagnosis was established postmortem when the cerebrospinal fluid (CSF) prion protein 14-3-3 tested positive. Creutzfeldt-Jakob disease must be considered in the differential diagnosis of rapidly progressive dementia as Connecticut accounts for approximately three of the more than 200 cases diagnosed nationally.
Davidsen, Jesper Rømhild; Bendstrup, Elisabeth; Henriksen, Daniel P
Background: Lung ultrasound (LUS) used to identify interstitial syndrome (IS) and pleural thickening related to diffuse parenchymal lung disease (DPLD) has shown significant correlations with ground glass opacity (GGO) on high-resolution computed tomography (HRCT). However, the applicability of LUS...... in patients with DPLD subtypes as rare cystic lung diseases has not previously been investigated. This study aimed to observe if distinctive LUS findings could be found in patients with lymphangioleiomyomatosis (LAM), pulmonary Langerhans cell histiocytosis (PLCH), and Birt-Hogg-Dubé syndrome (BHDS). Methods......: This single centre case-based cross-sectional study of patients diagnosed with LAM, PCLH and BHDS was conducted at a Danish DPLD specialist centre. Patients underwent clinical examination including LUS. LUS findings were compared to findings scored according to a modified Belmaati score on HRCT and reviewed...
Strickler, Alexis; Boza, Maria Lina; Koppmann, Andres; Gonzalez, Sergio
Interstitial lung disease (ILD) is rare and encompasses a heterogeneous group of diseases, and is even rarer in children than in adults. ILDs compromise more than 100 different entities, including pulmonary alveolar proteinosis (PAP). There are many causes of PAP in children, including surfactant protein gene mutations (SFTPB, SFTPC, ABCA3, TTF-1), GMCSF receptor mutations and antigranulocyte-macrophage colony-stimulating factor autoantibodies. We report a case of a 13-year-old Chilean girl who presented with an 8-month history of progressive exercise intolerance, fatigability and diminished school performance. Physical examination revealed resting tachypnoea, a few basal bilateral inspiratory crackles, and hypoxaemia on minimal exertion. Clinical suspicion and evaluation, including international collaboration, led to the diagnosis of autoimmune PAP and specific therapy for the condition.
... drugs for rare diseases or conditions; table of contents. 1.28-0 Section 1.28-0 Internal Revenue... Taxable Year § 1.28-0 Credit for clinical testing expenses for certain drugs for rare diseases or... 505(i). (d) Definition and special rules. (1) Definition of “rare disease or condition”. (i)...
Hannon, M J; Orr, C; Moran, C; Behan, L A; Agha, A; Ball, S G; Thompson, C J
Central diabetes insipidus is a rare clinical condition with a heterogenous aetiology. Up to 40% of cases are classified as idiopathic, although many of these are thought to have an autoimmune basis. Published data have suggested that anterior hypopituitarism is common in childhood-onset idiopathic diabetes insipidus. We aimed to assess the incidence of anterior hypopituitarism in a cohort of adult patients with idiopathic diabetes insipidus. We performed a retrospective review of the databases of two pituitary investigation units. This identified 39 patients with idiopathic diabetes insipidus. All had undergone magnetic resonance imaging scanning and dynamic pituitary testing (either insulin tolerance testing or GHRH/arginine and short synacthen testing) to assess anterior pituitary function. One patient had partial growth hormone deficiency; no other anterior pituitary hormonal deficits were found. Thirty-three percent had at least one autoimmune disease in addition to central diabetes insipidus. Our data suggest that anterior hypopituitarism is rare in adult idiopathic diabetes insipidus. Routine screening of these patients for anterior hypopituitarism may not, therefore, be indicated. The significant prevalence of autoimmune disease in this cohort supports the hypothesis that idiopathic diabetes insipidus may have an autoimmune aetiology. © 2012 Blackwell Publishing Ltd.
Erica GONZÁLEZ MARTÍN
Full Text Available Antecedents. The main objective of this study was to evaluate the quality of life in children and young people with rare diseases and intellectual disability, as well as to determine the incidence of certain predictors (i. e., gender, age, level of intellectual disability, type of school, type of illness and autonomous community in the criterion variable. Method. The KidsLife Scale was applied, a questionnaire based on the eight domain model of quality of life by Schalock and Verdugo. The sample comprised 103 participants with rare diseases and intellectual disability, aged between 3 and 21, who received supports in any organization providing educational, social, or health services. Results. The best scores were found in physical wellbeing, while the lowest were in social inclusion. The level of intellectual disability and support needs resulted in significant differences for the total score of the scale. Analyses by domains showed differences by gender, intellectual disability level, and type of schooling. Conclusions. The results argue for designing practices aimed to improve quality of life-related personal outcomes with regard to self-determination, inclusion, and interpersonal relationships.
Objective: Central diabetes insipidus is a rare clinical condition with a heterogenous aetiology. Up to 40% of cases are classified as idiopathic, though many of these are thought to have an autoimmune basis. Published data has suggested that anterior hypopituitarism is common in childhood onset idiopathic diabetes insipidus. We aimed to assess the incidence of anterior hypopituitarism in a cohort of adult patients with idiopathic diabetes insipidus. Design and Patients: We performed a retrospective review of the databases of two pituitary investigation units. This identified 39 patients with idiopathic diabetes insipidus. All had undergone MRI scanning and dynamic pituitary testing (either insulin tolerance testing or GHRH\\/arginine and short synacthen testing) to assess anterior pituitary function. Results: One patient had partial growth hormone deficiency; no other anterior pituitary hormonal deficits were found. 33% had at least one autoimmune disease in addition to central diabetes insipidus. Conclusions: Our data suggest that anterior hypopituitarism is rare in adult idiopathic diabetes insipidus. Routine screening of these patients for anterior hypopituitarism may not therefore be indicated. The significant prevalence of autoimmune disease in this cohort supports the hypothesis that idiopathic diabetes insipidus may have an autoimmune aetiology.
Kristof, Arnold S; Petrof, Basil J; Hamid, Qutayba; Kolb, Martin; Landry, Jennifer S; MacKenzie, Alex; McCormack, Francis X; Murawski, Inga J; Moss, Joel; Rauch, Frank; Rosas, Ivan O; Shapiro, Adam J; Smith, Benjamin M; Thomas, David Y; Trapnell, Bruce C; Young, Lisa R; Zariwala, Maimoona A
Rare respiratory diseases (RRDs) are a heterogeneous group of disorders that collectively represent a significant health care burden. In recent years, strong advocacy and policy initiatives have led to advances in the implementation of research and clinical care for rare diseases. The development of specialized centers and research networks has facilitated support for affected individuals as well as emerging programs in basic, translational, and clinical research. In selected RRDs, subsequent gains in knowledge have informed the development of targeted therapies and effective diagnostic tests, but many gaps persist. There was therefore a desire to identify the elements contributing to an effective translational research program in RRDs. To this end, a workshop was convened in October 2015 with a focus on the implementation of effective transnational research networks and collaborations aimed at developing novel diagnostic and therapeutic tools. Key elements included an emphasis on molecular pathogenesis, the continuing engagement of patient advocacy groups and policy makers, the effective use of preclinical models in the translational research pipeline, and the detailed phenotyping of patient cohorts. During the course of the workshop, current logistical and knowledge gaps were identified, and new solutions or opportunities were highlighted.
Johnson, Kimberly J; Mueller, Nancy L; Williams, Katherine; Gutmann, David H
Internet communication advances provide new opportunities to assemble individuals with rare diseases to online patient registries from wide geographic areas for research. However, there is little published information on the efficacy of different recruitment methods. Here we describe recruitment patterns and the characteristics of individuals with the self-identified autosomal dominant genetic disorder neurofibromatosis type 1 (NF1) who participated in an online patient registry during the 1-year period from 1/1/2012 to 12/31/2012. We employed four main mechanisms to alert potential participants to the registry: (1) Facebook and Google advertising, (2) government and academic websites, (3) patient advocacy groups, and (4) healthcare providers. Participants reported how they first heard about the registry through an online questionnaire. During the 1-year period, 880 individuals participated in the registry from all 50 U.S. States, the District of Columbia, Puerto Rico, and 39 countries. Facebook and Google were reported as referral sources by the highest number of participants (n=550, 72% Facebook), followed by healthcare providers (n=74), and government and academic websites (n=71). The mean participant age was 29±18 years and most participants reported White race (73%) and female sex (62%) irrespective of reported referral source. Internet advertising, especially through Facebook, resulted in efficient enrollment of large numbers of individuals with NF1. Our study demonstrates the potential utility of this approach to assemble individuals with a rare disease from across the world for research studies. © 2014 Wiley Periodicals, Inc.
Storgaard, Anders; Detlefsen, Sönke
Immunoglobulin G4-related disease (IgG4-RD) is an inflammatory and fibrotic disease with the potential to produce diffuse enlargement, massforming lesions or stenoses in a wide range of organs. Elevation of serum IgG4 concentration and high levels of IgG4-positive cells in the inflamed tissue are common denominators. Type 1 autoimmune pancreatitis is one of the main manifestations, and its recognition preceded the definition of IgG4-RD as a novel clinical entity. The aetiology, pathophysiology, epidemiology and clinical long-term outcome of IgG4-RD are not fully elucidated. Steroids are effective in most patients, sometimes combined with other antiinflammatory drugs.
Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD). These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case-control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer's disease in seven independent case-control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer's disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer's disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer's disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-β precursor protein (APP) and extracellular Aβ42 and Aβ40 (the 42- and 40-residue isoforms of the amyloid-β peptide), and knockdown of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex
Eduardo Alonso Serrano-Brambila; Efraín Maldonado-Alcaraz; Xavier Abraham Espinoza-Guerrero; Jorge Moreno-Palacios; Guillermo Antonio Ixquiac-Pineda; Edgar Cárdenas-Rodríguez
Objetivo: Describir la técnica de cabestrillo subtrigonal con fascia abdominal y demostrar su utilidad en la resolución de la incontinencia urinaria de esfuerzo compleja. Material y métodos: Estudio de cohorte longitudinal y observacional en mujeres adultas que acudieron al Servicio de Urodinamia, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, para tratamiento de incontinencia urinaria de esfuerzo recidivante o con factores de riesgo para recidiva, asociada o no a incontinencia...
Development of a database to record orofacial manifestations in patients with rare diseases: a status report from the ROMSE (recording of orofacial manifestations in people with rare diseases) database.
Hanisch, M; Hanisch, L; Benz, K; Kleinheinz, J; Jackowski, J
The aim of this working group was to establish a ROMSE (recording of orofacial manifestations in people with rare diseases) database to provide clinicians, patients, and their families with better information about these diseases. In 2011, we began to search the databases Orphanet, OMIM(®) (Online Mendelian Inheritance in Man(®)), and PubMed, for rare diseases with orofacial symptoms, and since 2013, the collected information has been incorporated into a web-based, freely accessible database. To date, 471 rare diseases with orofacial signs have been listed on ROMSE, and 10 main categories with 99 subcategories of signs such as different types of dental anomalies, changes in the oral mucosa, dysgnathia, and orofacial clefts, have been defined. The database provides a platform for general clinicians, orthodontists, and oral and maxillofacial surgeons to work on the best treatments.
Stallone, Giovanni; Infante, Barbara; Cormio, Luigi; Macarini, Luca; Grandaliano, Giuseppe
BACKGROUND Benign multicystic peritoneal mesothelioma (BMPM) is a rare intra-abdominal tumor. Although considered by many to be benign, this tumor has a high local recurrence rate. Because of its rarity, preoperative diagnosis is difficult and its origin and pathogenesis are uncertain. There are no evidence-based treatment strategies for BMPM. It is agreed that the best treatment strategy for BMPM is the combination of surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). An increasing body of evidence supports a pivotal role of the cytoplasmic serine/threonine kinase mTOR in the development and progression of several neoplastic diseases and specific mTOR inhibitors, including rapamycin, have been suggested as potential therapeutic options for different cancers. CASE REPORT A 65-year-old male with end-stage renal disease on hemodialysis for seven years presented with BMPM. He underwent surgery to remove multiple peritoneal cysts, but four months later he experienced a recurrence of the disease. Immunohistochemistry of the cysts demonstrated a high level of phosphorylation of p70S6 kinase, a downstream mTOR target, and since a target therapy that blocks PI3K/Akt/mTOR pathway has been shown to have a scientific and logical rationale to treat this rare intra-abdominal neoplasia, we started the patient on low dose rapamycin therapy, an mTOR inhibitor. Long-term mTOR inhibition resulted in a complete and stable remission of BMPM. CONCLUSIONS The current case is the first report of BMPM successfully treated with rapamycin, which resulted in a long-lasting response to mTOR inhibition.
Grove, Megan L.; Naj, Adam; Vronskaya, Maria; DeStefano, Anita L.; Brody, Jennifer A.; Smith, Albert V.; Amin, Najaf; Sims, Rebecca; Ibrahim-Verbaas, Carla A.; Choi, Seung-Hoan; Lopez, Oscar L.; Beiser, Alexa; Ikram, M. Arfan; Garcia, Melissa E.; Hayward, Caroline; Ripatti, Samuli; Franks, Paul W.; Hallmans, Göran; Rolandsson, Olov; Jansson, Jan-Håkon; Porteous, David J.; Salomaa, Veikko; Eiriksdottir, Gudny; Rice, Kenneth M.; Bellen, Hugo J.; Levy, Daniel; Uitterlinden, Andre G.; Emilsson, Valur; Rotter, Jerome I.; Aspelund, Thor; O’Donnell, Christopher J.; Fitzpatrick, Annette L.; Launer, Lenore J.; Hofman, Albert; Wang, Li-San; Williams, Julie; Schellenberg, Gerard D.; Boerwinkle, Eric; Psaty, Bruce M.; Seshadri, Sudha; Shulman, Joshua M.; Gudnason, Vilmundur; van Duijn, Cornelia M.
We performed an exome-wide association analysis in 1393 late-onset Alzheimer’s disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (~0.5% versus <0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES sub-study, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5–15.9), p = 6.6x10-9]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the β-amyloid cascade. PMID:27764101
Hampson, Lisa V; Whitehead, John; Eleftheriou, Despina; Brogan, Paul
This paper considers the design and interpretation of clinical trials comparing treatments for conditions so rare that worldwide recruitment efforts are likely to yield total sample sizes of 50 or fewer, even when patients are recruited over several years. For such studies, the sample size needed to meet a conventional frequentist power requirement is clearly infeasible. Rather, the expectation of any such trial has to be limited to the generation of an improved understanding of treatment options. We propose a Bayesian approach for the conduct of rare-disease trials comparing an experimental treatment with a control where patient responses are classified as a success or failure. A systematic elicitation from clinicians of their beliefs concerning treatment efficacy is used to establish Bayesian priors for unknown model parameters. The process of determining the prior is described, including the possibility of formally considering results from related trials. As sample sizes are small, it is possible to compute all possible posterior distributions of the two success rates. A number of allocation ratios between the two treatment groups can be considered with a view to maximising the prior probability that the trial concludes recommending the new treatment when in fact it is non-inferior to control. Consideration of the extent to which opinion can be changed, even by data from the best feasible design, can help to determine whether such a trial is worthwhile. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons, Ltd. PMID:24957522
Full Text Available We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L in TM2D3 was enriched in Icelanders (~0.5% versus <0.05% in other European populations. In 433 LOAD cases and 3903 controls from the Icelandic AGES sub-study, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI = 7.5 (3.5-15.9, p = 6.6x10-9]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the β-amyloid cascade.
Full Text Available Klippel Trenaunay Weber syndrome (KTWS is a rare disease characterized by hemihypertrophy, variceal enlargement of the veins, and arteriovenous (AV malformations. Renal involvement in KTWS is not known except in rare case reports. Herein, we present a case of KTWS with unilateral polycystic kidney. A 52-year-old male was admitted due to pain left lumbar region for the last three months. The physical findings were increased diameter and increased length of the left leg compared with the right one, diffuse variceal enlargements on left leg, portwine stain on left side on neck, thorax, abdomen, left upper limb and left lower limb and a few hemangiomatous lesions on the left leg. Radiographic findings were cystic lesions in the left kidney, varicose veins in left leg, and hypertrophy of the soft tissues of the proximal left leg. Color Doppler of left lower limb showed incompetence of the saphenofemoral junction. He was diagnosed to have KTWS with these findings. Renal function tests of the patient were in the normal range. Patient's only complain was left lumbar region pain, mild in intensity. Patient was managed symptomatically. [Int J Res Med Sci 2016; 4(5.000: 1760-1762
Hampson, Lisa V; Whitehead, John; Eleftheriou, Despina; Brogan, Paul
This paper considers the design and interpretation of clinical trials comparing treatments for conditions so rare that worldwide recruitment efforts are likely to yield total sample sizes of 50 or fewer, even when patients are recruited over several years. For such studies, the sample size needed to meet a conventional frequentist power requirement is clearly infeasible. Rather, the expectation of any such trial has to be limited to the generation of an improved understanding of treatment options. We propose a Bayesian approach for the conduct of rare-disease trials comparing an experimental treatment with a control where patient responses are classified as a success or failure. A systematic elicitation from clinicians of their beliefs concerning treatment efficacy is used to establish Bayesian priors for unknown model parameters. The process of determining the prior is described, including the possibility of formally considering results from related trials. As sample sizes are small, it is possible to compute all possible posterior distributions of the two success rates. A number of allocation ratios between the two treatment groups can be considered with a view to maximising the prior probability that the trial concludes recommending the new treatment when in fact it is non-inferior to control. Consideration of the extent to which opinion can be changed, even by data from the best feasible design, can help to determine whether such a trial is worthwhile.
Full Text Available Dysplasia epiphysealis hemimelica, also known as Trevor's disease, is an extremely rare skeletal developmental disorder of unknown etiology, characterized by an osteocartilaginous outgrowth of one or more epiphyses or of a tarsal bone during childhood. It is a rare skeletal hemimelica disorder characterized by asymmetric growth of cartilage in one or more epiphyses. Due to the unusual presentation and variability of the picture, there is no standardized treatment and outcome is very different. Also such an unusual, unique case with craniofacial manifestations has not been reported in the literature. We report a case of a 14-year-old male, who complained of irregularly placed teeth in upper and lower front teeth region. On general physical examination we noticed some skeletal abnormalities with the patient and hence we subjected him to radiographic investigations. The images were consistent with epiphyseal dysplasia hemimelica. The prognosis of DEH is variable and depends basically on its location and size. Carriers of this unusual dysplasia should be periodically monitored for the risk of recurrence. [Int J Res Med Sci 2015; 3(4.000: 1018-1024
Full Text Available A leading cause of death in western countries is sudden cardiac death, and can be associated with genetic disease. Next-generation sequencing has allowed thorough analysis of genes associated with this entity, including, most recently, titin. We aimed to identify potentially pathogenic genetic variants in titin. A total of 1126 samples were analyzed using a custom sequencing panel including major genes related to sudden cardiac death. Our cohort was divided into three groups: 432 cases from patients with cardiomyopathies, 130 cases from patients with channelopathies, and 564 post-mortem samples from individuals showing anatomical healthy hearts and non-conclusive causes of death after comprehensive autopsy. None of the patients included had definite pathogenic variants in the genes analyzed by our custom cardio-panel. Retrospective analysis comparing the in-house database and available public databases also was performed. We identified 554 rare variants in titin, 282 of which were novel. Seven were previously reported as pathogenic. Of these 554 variants, 493 were missense variants, 233 of which were novel. Of all variants identified, 399 were unique and 155 were identified at least twice. No definite pathogenic variants were identified in any of genes analyzed. We identified rare, mostly novel, titin variants that seem to play a potentially pathogenic role in sudden cardiac death. Additional studies should be performed to clarify the role of these variants in sudden cardiac death.
Full Text Available Isolated cervical nodal involvement of Castleman’s disease is very rare, accounting for 6% of all cases. Of the two histopathological variants of Castleman’s disease, the hyaline-vascular type is more common as seen in our patient and carries a better prognosis than the plasma cell type.
Full Text Available Pyrexia of unknown origin (PUO is a common problem in medical practice. Patients suffer from fever for long period but initial relevant investigations remain normal. Infection is the most common cause of PUO in developing countries. Other causes are lymphoma, myeloma, connective tissue diseases (CTD, sarcoidosis and malignancy etc. In our country, where no cause can be identified, a usual practice is to start anti-tubercular drugs. We report a patient who was suffering from prolonged fever and usual investigations were within normal limit except high erythrocyte sedimentation rate. In spite of having 6 months anti-tubercular drugs, the patient did not respond. Thorough examination revealed a paraaortic mass which was reconfirmed by ultrasound of abdomen. Laparotomy revealed a mesenteric lymph node that was removed. Histopathologically it was diagnosed as a case of CASTLEMAN'S DISEASE which is a rare cause of PUO. On removal of the lymph node, the patient improved dramatically. Key words: Castleman's disease; PUO DOI: 10.3329/bsmmuj.v2i2.4764 BSMMU J 2009; 2(2: 85-87
Kailash Chandra Patra
Full Text Available Huntington′s disease (HD is a rare dominantly inherited neurodegenerative disorder characterized clinically by a combination of abnormal involuntary (choreic movements, neuropsychiatric manifestations, and dementia. It is caused by an unstable CAG repeat expansion in the gene IT15 which encodes a Huntingtin protein. We present a case of a 9 year old boy who had developmental regression starting from the age of 8 years of age along with resistant seizures and signs of cerebellar involvement with absence of chorea and is on anticonvulsants, baclofen, and tetrabenzine. As is expected in a case of childhood-onset HD, our patient is rapidly deteriorating and is currently in the terminal phase of his illness along with resistant convulsions.
Gosal Gurinder S
Full Text Available Congenital muscular dystrophy (CMD is a heterogeneous group of disorders characterized by muscular hypotonia since birth and the histologic features of muscular dystrophy. Syndromic congenital muscular dystrophies are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, lissencephaly, and eye anomalies. We present a case of a rare form of syndromic congenital muscular dystrophy in an eight year old girl, born of first- degree consanguinity. She had: global developmental delay; a seizure disorder; hypotonia; progressive muscle contractures including bilateral symmetrical flexion contractures of hips, knees, equinus contracture and thoracolumbar scoliosis; diminished deep tendon reflexes: bilateral premature cataract; pseudophakia; and nystagmus. The patient was also highly myopic. Based on clinical features, muscle biopsy and MRI of the brain, a diagnosis of muscle- eye- brain disease was made. Identification of these patients may help to prevent this crippling disorder in the future siblings of probands by utilizing genetic counselling and mutation analysis.
Verma, Rajesh; Bhandari, Aveg; Tiwari, Navin; Chaudhari, Tejendra S
Wilson disease (WD) is one of the few inherited but treatable disorder mainly affecting the liver and brain resulting in severe disability or death if left untreated. Hence, it is important to keep a high index of suspicion for diagnosing this clinical entity in appropriate clinical settings. The clinical presentation can be quite variable and they may present solely with neurological features sans hepatic symptoms. Such neurological manifestations usually follow subacute to chronic course. Acute onset anarthria as the heralding and predominant presenting feature has been rarely reported in the literature. We reported a case of a 12-year-old girl who presented with acute onset anarthria and dystonia of 1-month duration. On further evaluation, a diagnosis of WD was made. The patient showed partial improvement after she was started on copper chelating agents and anticholinergics.
Chadwick, Thomas; Katti, Ashok; Arthur, James
A rare complication of diverticular disease is the formation of fistulas, most commonly either colo-vesical or colo-vaginal. We present the unusual case of a perforated sigmoid diverticulum forming a colo-gluteal fistula and presenting initially as a gluteal abscess in an otherwise asymptomatic patient. After drainage of the gluteal abscess, the patient re-presented with faecal loss from the abscess drainage site. Imaging revealed fistulous communication between the sigmoid and the left obturator internus muscle, tracking to the gluteus maximus with associated abscess and cutaneous communication to the site of previous drainage. The patient underwent an emergency Hartmann's procedure with lay open/abscess drainage of the gluteal cavity. Post-operatively the patient experienced continuing discharge from the gluteal fistula despite repeated drainage and debridement causing considerable morbidity, inconvenience and misery. Clinicians should maintain a high index of suspicion when presented with a gluteal abscess and should consider the possibility of an intra-abdominal source.
Yener, Nese; Ilter, Erdin; Midi, Ahmet
Xanthogranulomatous salpingitis (XGS) is a rare form of chronic inflammation of the fallopian tubes. A 41-year old woman with a history of secondary infertility for 2 years is presented. The patient underwent bilateral salpingooopherectomy with presumptive diagnosis of adnexal mass with cystic component. Intraoperative pathology consultation was done. The diagnosis of bilateral XGS associated with chronic active follicular salpingitis was made. XGS is reported to be caused by an unsuccesfully treated pelvic inflammatory disease. Its association with chronic active follicular salpingitis has not been previously reported. Chronic active follicular salpingitis with xanthogranulomatous inflammation might give the impression of a cystic adnexal mass with septations on preoperative pelvic computed tomography. Frozen sections are necessary to rule out malignancy as done in our case.
Kirova, Y M; Feuilhade, F; Belda-Lefrère, M A; Le Bourgeois, J P
A case report of intrauterine device (IUD)-associated tubo-ovarian actinomycosis is presented. The patient was a 37-year-old nulliparous woman with IUD usage for the last four years. She presented anemia and weight lost of 8 kg. Ultrasound and computed tomography showed an unilateral large mass in the right adnexum adherent to the uterus and compressing the urinary bladder. Preoperative diagnosis of ovarian cancer with liver metastases was made. Bilateral salpingoophorectomy and total abdominal hysterectomy were performed. After pathological and biological analyses, actinomycosis was diagnosed and the patient was treated postoperatively with penicillin. The purpose of this article is to add to the literature a new case of this rare disease which clinically mimics ovarian cancer.
Full Text Available The human immune system depends on the activity of cytotoxic T lymphocytes, Natural Killer cells, and NKT cells in order to fight off a viral infection. Understanding the molecular mechanisms during this process and the role of individual proteins was greatly improved by the study of Familial Hemophagocytic Lymphohistiocytosis (FHL. Since 1999, genetic sequencing is the gold standard to classify patients into different subgroups of FHL. The diagnosis, once based on a clinical constellation of abnormalities, is now strongly supported by the results of a functional flow-cytometry screening, which directs the genetic study. A few additional congenital immune deficiencies can also cause a resembling or even identical clinical picture to FHL. As in many other rare human disorders, the collection and analysis of a relatively large number of cases in registries is crucial to draw a complete picture of the disease. The conduction of prospective therapeutic trials allows investigators to increase the awareness of the disease and to speed up the diagnostic process, but also provides important functional and genetic confirmations. Children with confirmed diagnosis may undergo hematopoietic stem cell transplantation, which is the only cure known to date. Moreover, detailed characterization of these rare patients helped to understand the function of individual proteins within the exocytic machinery of CTL, NK and NKT cells. Moreover, identification of these genotypes also provides valuable information on variant phenotypes, other than FHL, associated with biallelic and monoallelic mutations in the FHL-related genes.In this review we describe how detailed characterization of patients with genetic HLH has resulted in improvement in knowledge regarding contribution of individual proteins to the functional machinery of cytotoxic T-cells and NK cells. The review also details how identification of these genotypes has provided valuable information on variant
Daoud, Hussein; Luco, Stephanie M.; Li, Rui; Bareke, Eric; Beaulieu, Chandree; Jarinova, Olga; Carson, Nancy; Nikkel, Sarah M.; Graham, Gail E.; Richer, Julie; Armour, Christine; Bulman, Dennis E.; Chakraborty, Pranesh; Geraghty, Michael; Lines, Matthew A.; Lacaze-Masmonteil, Thierry; Majewski, Jacek; Boycott, Kym M.; Dyment, David A.
Background: Rare diseases often present in the first days and weeks of life and may require complex management in the setting of a neonatal intensive care unit (NICU). Exhaustive consultations and traditional genetic or metabolic investigations are costly and often fail to arrive at a final diagnosis when no recognizable syndrome is suspected. For this pilot project, we assessed the feasibility of next-generation sequencing as a tool to improve the diagnosis of rare diseases in newborns in the NICU. Methods: We retrospectively identified and prospectively recruited newborns and infants admitted to the NICU of the Children’s Hospital of Eastern Ontario and the Ottawa Hospital, General Campus, who had been referred to the medical genetics or metabolics inpatient consult service and had features suggesting an underlying genetic or metabolic condition. DNA from the newborns and parents was enriched for a panel of clinically relevant genes and sequenced on a MiSeq sequencing platform (Illumina Inc.). The data were interpreted with a standard informatics pipeline and reported to care providers, who assessed the importance of genotype–phenotype correlations. Results: Of 20 newborns studied, 8 received a diagnosis on the basis of next-generation sequencing (diagnostic rate 40%). The diagnoses were renal tubular dysgenesis, SCN1A-related encephalopathy syndrome, myotubular myopathy, FTO deficiency syndrome, cranioectodermal dysplasia, congenital myasthenic syndrome, autosomal dominant intellectual disability syndrome type 7 and Denys–Drash syndrome. Interpretation: This pilot study highlighted the potential of next-generation sequencing to deliver molecular diagnoses rapidly with a high success rate. With broader use, this approach has the potential to alter health care delivery in the NICU. PMID:27241786
In Wegener's granulomatosis peripheral nerves are more often involved than central nervous structures; functional psychoses are secondary e.g. to renal complications. Neurologic-psychiatric symptoms are varied and result from local spread from the upper respiratory tract with separate granulomata and vasculitis. Striped muscle is involved in about 10% of cases. Specific vegetative disturbances of function do not appear to occur. This is also true for Granuloma gangrenescens. Its multicentric inflammatory, ulcerating and necrotic foci involve midline structures and often start at the anterior neuroporus. Becet's disease, however, shows clear characteristic localisation, symmetry of various dermatologic phenomena in the extremities and the almost obligatory involvement of mouth, stomach and the genitals and their surroundings. This one may assume to be due to a mesencephalic parasympathicotonic reaction as the basis for the occurrence of perioral and acro-syndroms after Fischer-Brügge and Sunder-plassmann. Some similarity with the localization of other collagenous diseases is evident. The anterior basal ganglia represent a favored focus where e.g. initial, imcomplete and readily recurrent processes, possibly of an exsudative nature, may start off neurovascular changes of limited areas without necessarily producing clinically detectable signs of the usual neurologic-psychiatric type. In Behcet's disease, rather as in scleroderma, the nervous system appears to be decisively involved. About one third of the cases show changes in the nervous system ("Neuro-Behcet" in the usual sense) with little peripheral signs and rare myositis. But Behcet's disease may also-like erythematodes or progressive sclerodermia-simulate a disseminated encephalomyelitis. The pathogenetic factors of Reiter's syndrome appear to be closely related. The relatively constant main symptoms are also localized and permit the conclusion that they depend on vasomotorically linked innervation of the
Mehta, Sudhir Kumar; Bala, Jyoti; Zaman, Muzzafar; Mittal, Amit; Gupta, Guarav; Rudra, Samer; Singal, Samita
Introduction Polymastia and polythelia may be asymptomatic or cause pain, restriction of arm movement, milk discharge, cosmetic problems or anxiety. Cosmesis is the main indication for surgical excision of accessory breasts in axilla. In addition it also confirms the diagnosis and allays the patient’s fear of harbouring a malignancy. Aim To evaluate the presentation of symptoms, investigations required for diagnosis and the management to improve the treatment protocols in patients with breast diseases. Materials and Methods This retrospective study on breast diseases presenting as supernumerary breasts and nipples was conducted in the Department of Surgery between January 2013 and January 2016 at MMIMS Research and hospital, Mullana, Ambala. Patients were evaluated for breast diseases, either benign or malignant in both genders. A total of 32 cases diagnosed as accessory breasts disease were retrieved from the hospital archive. The clinical and radiological evaluation was done in the form of ultrasound and mammography wherever necessary. Accessory breast tissues were excised under general anesthesia and histopathological examinations were done. Results Out of 32 cases: 1(3.125%) male patient had unilateral and 1(3.125%) male had bilateral accessory nipple, 7 (21.87%) females had unilateral and 1(3.125%) had bilateral accessory nipple, 1 (3.125%) diagnosed as accessory axillary fibroadenoma in female, 16(50%) presented as unilateral and 5 (15.62%) had bilateral swelling in the axilla as accessory breast. Patients underwent surgical excision and in 8(25%) cases z- shaped incision was made in view of better cosmesis. Patients were followed up upto 6 months postoperatively. There were no residual swelling and movements of the arm over the shoulder joint were normal. In 3(9.37%) cases, wound dehiscence occurred; in 2 (6.25%) cases lymphoedema formation was seen. These were successfully managed conservatively. Conclusion As breast swellings either fibroadenoma or
Full Text Available GGGGCC repeat expansions in the C9orf72 gene have been identified as a major contributing factor in patients with amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD. Given the overlapping of clinical phenotypes and pathological characteristics between these two diseases and Alzheimer’s disease (AD, Parkinson’s disease (PD and essential tremor (ET, we speculated regarding whether C9orf72 repeat expansions also play a major role in these three diseases. Using the repeat-primed polymerase chain reaction method, we screened for C9orf72 in three groups of patients with PD (n=911, AD (n=279, and ET (n=152 in the Chinese Han population. There were no pathogenic repeats (>30 repeats detected in either the patients or controls (n=314, which indicated that the pathogenic expansions of C9orf72 might be rare in these three diseases. However, the analysis of the association between the number of repeats (p=0.001, short/intermediate genotype (short: <7 repeats; intermediate: ≥7 repeats (odds ratio 1.37 [1.05, 1.79], intermediate/intermediate genotype (Odds ratio 2.03 [1.17, 3.54] and PD risks indicated that intermediate repeat alleles could act as contributors to PD. To the best of our knowledge, this study is the first to reveal the correlation between C9orf72 and Chinese PD, AD or ET patients. Additionally, the results of this study suggest the novel idea that the intermediate repeat allele in C9orf72 is most likely a risk factor for PD.
Wandel, Simon; Neuenschwander, Beat; Röver, Christian; Friede, Tim
Clinical research and drug development in orphan diseases are challenging, since large-scale randomized studies are difficult to conduct. Formally synthesizing the evidence is therefore of great value, yet this is rarely done in the drug-approval process. Phase III designs that make better use of phase II data can facilitate drug development in orphan diseases. A Bayesian meta-analytic approach is used to inform the phase III study with phase II data. It is particularly attractive, since uncertainty of between-trial heterogeneity can be dealt with probabilistically, which is critical if the number of studies is small. Furthermore, it allows quantifying and discounting the phase II data through the predictive distribution relevant for phase III. A phase III design is proposed which uses the phase II data and considers approval based on a phase III interim analysis. The design is illustrated with a non-inferiority case study from a Food and Drug Administration approval in herpetic keratitis (an orphan disease). Design operating characteristics are compared to those of a traditional design, which ignores the phase II data. An analysis of the phase II data reveals good but insufficient evidence for non-inferiority, highlighting the need for a phase III study. For the phase III study supported by phase II data, the interim analysis is based on half of the patients. For this design, the meta-analytic interim results are conclusive and would justify approval. In contrast, based on the phase III data only, interim results are inconclusive and require further evidence. To accelerate drug development for orphan diseases, innovative study designs and appropriate methodology are needed. Taking advantage of randomized phase II data when analyzing phase III studies looks promising because the evidence from phase II supports informed decision-making. The implementation of the Bayesian design is straightforward with public software such as R.
Full Text Available Acute cholecystitis leading to gallbladder perforation is relatively common. However, transhepatic perforation of the gallbladder leading to biliary peritonitis is very rare. We present a rare case of biliary peritonitis caused by transhepatic perforation of the gallbladder.
Bombelli, Francesco; Stojkovic, Tanya; Dubourg, Odile; Echaniz-Laguna, Andoni; Tardieu, Sandrine; Larcher, Kathy; Amati-Bonneau, Patrizia; Latour, Philippe; Vignal, Odile; Cazeneuve, Cécile; Brice, Alexis; Leguern, Eric
Axonal Charcot-Marie-Tooth disease (CMT) is genetically heterogeneous, with 11 genes identified. Axonal CMT has most frequently been associated with mutations in the MFN2 gene (CMT2A). To describe the clinical and molecular features of CMT2A, to delineate prognostic factors, to understand connections between a certain phenotype and more serious clinical consequences, and to identify interactions among the associated genes. We describe the clinical, molecular, electrophysiological, and additional features of 43 patients with CMT2A. The degree of physical disability was determined by the CMT neuropathy score and adapted to the CMT neuropathy score gradient to evaluate the clinical course. We evaluated all data within the context of the most recent and important publications concerning this issue. Twenty-five patients had early-onset CMT2A and severe functional disability, with 9 being wheelchair bound, and 18 had late-onset disease and a milder phenotype. Optic atrophy, vocal cord palsy, and auditory impairment were observed in 5, 6, and 2 patients, respectively. Among the 24 patients who underwent magnetic resonance imaging of the spinal cord, 6 had evidence of spinal atrophy with or without hydromyelia. In 1 patient, magnetic resonance imaging revealed hydrocephalus. Twenty different MFN2 mutations were identified, and 14 were considered new variants. Their transmission was predominantly autosomal dominant, with vertical transmission in 8 and de novo occurrence in 3. However, we also identified rare types of transmission, especially a germinal mosaicism and an autosomal recessive inheritance. One patient carried a rare variant in the GDAP1 gene and another in the OPA1 gene in association with MFN2 mutation. Charcot-Marie-Tooth disease type 2A associated with MFN2 mutations is clinically very heterogeneous. Ranging from a mild to a severe form, CMT2A exhibits various types of transmission. Optic atrophy and vocal cord palsy were observed in patients with severe
Yamada, Rin; Horiguchi, Shin-ichiro; Yamashita, Toshinari; Kamisawa, Terumi
IgG4-related disease (IgG4-RD) is characterised by high serum concentrations of IgG4, dense lymphoplasmacytic infiltrates, storiform fibrosis and increased IgG4-positive plasma cells in tissues. This systemic disease occurs in various organs metachronously, but IgG4-related mastitis appears extremely rare. We report a case of IgG4-related mastitis, radiologically considered to represent breast cancer mainly composed of intraductal component and requiring histological differentiation from mucosa-associated lymphoid tissue (MALT) lymphoma. The breast mass disappeared with steroid therapy. When patients have a breast mass, regardless of the presence or absence of IgG4-RD, IgG4-related mastitis should be considered in addition to breast cancer. If histological findings show dense lymphoplasmacytic infiltrates, IgG4-related mastitis should be suspected in addition to malignant lymphoma, and lack of monoclonality should be confirmed. To avoid unnecessary surgery or chemotherapy, knowledge and accurate diagnosis of the entity of IgG4-related mastitis is necessary. 2016 BMJ Publishing Group Ltd.
Full Text Available Primary adult hypertrophic stenosis is uncommon with an uncertain etiopathogenesis and associated gastric outlet obstruction mimics gastric carcinoma. We present a case of AHPS as sequel of peptic ulcer disease in a 72 year old male. With the advent of proton pump inhibitors as a mainstay of medical therapy, complication into gastric outlet obstruction is a rare disease today. Upper GI endoscopy revealed a distended stomach, residual food and a hyperemic bulky pylorus not accommodating the endoscope. Barium meal follow-through revealed a dilated stomach and minimal barium passing through the pylorus. Histological analysis revealed mild dysplasia at the focus with dense inflammatory infiltrates composed of lymphocytes and eosinophils in the lamina propria. No evidence of malignancy was noted, favouring chronic gastritis. The condition mimics other forms of proliferative disorders like carcinoma, gastrointestinal stromal tumors. We present the clinical findings, imaging analysis and discuss etiopathogenesis and management. [Int J Res Med Sci 2016; 4(5.000: 1730-1732
Full Text Available Localized cystic disease of kidney (LCDK is a rare, non-familial, non-progressive renal disorder that is not associated with cysts or disorders in other organs. Only a few cases have been reported in the literature. While this condition is morphologically identical to the autosomal dominant form of polycystic kidney disease, it is not inherited and is not associated with significant deterioration of renal function. We present a case of a 16-year-old male patient who suffered from hypertension for over two years. On imaging we found several, variable-sized cysts in the upper half of the right kidney. The left kidney and lower segment of the right kidney were normal. Selective renal vein catheterization and sampling showed markedly elevated renin level in the right upper segmental vein (92 pg/ml, normal value: 11-33 pg/ml. The patient underwent a right upper heminephrectomy and histopathology was suggestive of LCDK. After surgery, the patient′s blood pressure returned to normal levels without any need of antihypertensive medication and he is under follow-up on outpatient basis for the past two years.
Full Text Available ABSTRACT Purpose: Bladder tumors are rare in children and adolescents. For this reason, the diagnosis is sometimes delayed in pediatric patients. We aimed to describe the diagnosis, treatment, and follow-up methods of bladder urothelial neoplasms in children and adolescents. Materials and Methods: We carried out a retrospective multicenter study involving patients who were treated between 2008 and 2014. Eleven patients aged younger than 18 years were enrolled in the study. In all the patients, a bladder tumor was diagnosed using ultrasonography and was treated through transurethral resection of the bladder (TURBT. Results: Nine of the 11 patients (82% were admitted with gross hematuria. The average delay in diagnosis was 3 months (range, 0–16 months until the ultrasonographic diagnosis was performed from the first episodes of macroscopic hematuria. A single exophytic tumor (1–4cm was present in each patient. The pathology of all patients was reported as superficial urothelial neoplasm: two with papilloma, one with papillary urothelial neoplasm of low malignant potential (PUNLMP, four with low grade pTa, and four with low grade pT1. No recurrence was observed during regular cystoscopic and ultrasonographic follow-up. Conclusions: Regardless of the presence of hematuria, bladder tumors in children are usually not considered because urothelial carcinoma in this population is extremely rare, which causes a delay in diagnosis. Fortunately, the disease has a good prognosis and recurrences are infrequent. Cystoscopy may be unnecessary in the follow-up of children with bladder tumors. We believe that ultrasonography is sufficient in follow-up.
Alberto Acevedo Rehbein
Full Text Available Este artículo analiza las cláusulas de mejores esfuerzos (best efforts. En la primera parte, el autor analiza desde la óptica del common law cómo las cortes estadounidenses han definido y determinado el alcance de las cláusulas de mejores esfuerzos. Posteriormente, se hace un análisis comparativo frente al ordenamiento jurídico colombiano con el propósito de determinar la aplicación de este tipo de cláusulas en Colombia. La tesis central del artículo es que las cláusulas de mejores esfuerzos no son usadas en Colombia puesto que nuestro ordenamiento cuenta con una figura equivalente, la teoría de las obligaciones de medios. Debido a la incorporación jurisprudencial en Colombia de la clasificación de obligaciones de medios y resultado, existe en los abogados colombianos la noción de que las obligaciones en general se deben ejecutar empleando los mejores esfuerzos. Por ende, incluir dichas cláusulas en los contratos resultaría superfluo. En suma este artículo nos ayuda a entender desde un punto de vista comparativo el alcance de las cláusulas de mejores esfuerzos en Estados Unidos y en Colombia.
Hendriksz, Christian J; Anheim, Mathieu; Bauer, Peter; Bonnot, Olivier; Chakrapani, Anupam; Corvol, Jean-Christophe; de Koning, Tom J; Degtyareva, Anna; Dionisi-Vici, Carlo; Doss, Sarah; Duning, Thomas; Giunti, Paola; Iodice, Rosa; Johnston, Tracy; Kelly, Dierdre; Klünemann, Hans-Hermann; Lorenzl, Stefan; Padovani, Alessandro; Pocovi, Miguel; Synofzik, Matthis; Terblanche, Alta; Then Bergh, Florian; Topçu, Meral; Tranchant, Christine; Walterfang, Mark; Velten, Christian; Kolb, Stefan A
Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups ("clinical niches") have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes. Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included. Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches. Several clinical niches have been identified that harbor patients at increased risk of NP-C.
Peces, R; Alvarez-Navascués, R
Renal cell carcinoma (RCC) is a disorder encompassing a wide spectrum of pathological renal lesions. Coexistence of unilateral RCC and associated pathology in the contralateral kidney is an unusual and challenging therapeutic dilemma that can result in renal failure. So far, data on unilateral RCC with chronic renal failure necessitating renal replacement therapy have not been published. The aim of the present study was to evaluate the incidence of end-stage renal disease (ESRD) from unilateral RCC, and to assess the associated pathology and possible pathogenic factors. In 1999, a survey of the 350 patients treated by chronic dialysis in Asturias, Spain, was carried out to identify and collect clinical information on patients with primary unilateral RCC whilst on their renal replacement programme. Seven patients were identified as having ESRD and unilateral RCC, giving an incidence of 2% of patients treated by dialysis. There was a wide spectrum of associated disease and clinical presentation. All patients underwent radical or partial nephrectomy and were free of recurrence 6--64 months after surgery. Six patients were alive and free of malignancy recurrence for 6--30 months after the onset of haemodialysis. ESRD is rare in association with unilateral RCC, but does contribute to significant morbidity. However, the data presented here are encouraging and suggest that cancer-free survival with renal replacement therapy can be achieved in such patients.
Full Text Available Over 300 million people are affected by about 7000 rare diseases globally. There are tremendous resource limitations and challenges in driving research and drug development for rare diseases. Hence, innovative approaches are needed to identify potential solutions. This review focuses on the resources developed over the past years for analysis of genome data towards understanding disease biology especially in the context of mitochondrial diseases, given that mitochondria are central to major cellular pathways and their dysfunction leads to a broad spectrum of diseases. Platforms for collaboration of research groups, clinicians and patients and the advantages of community collaborative efforts in addressing rare diseases are also discussed. The review also describes crowdsourcing and crowdfunding efforts in rare diseases research and how the upcoming initiatives for understanding disease biology including analyses of large number of genomes are also applicable to rare diseases.
Neeraj Kumar Rajput
Full Text Available Over 300 million people are affected by about 7000 rare diseases globally. There are tremendous resource limitations and challenges in driving research and drug development for rare diseases. Hence, innovative approaches are needed to identify potential solutions. This review focuses on the resources developed over the past years for analysis of genome data towards understanding disease biology especially in the context of mitochondrial diseases, given that mitochondria are central to major cellular pathways and their dysfunction leads to a broad spectrum of diseases. Platforms for collaboration of research groups, clinicians and patients and the advantages of community collaborative efforts in addressing rare diseases are also discussed. The review also describes crowdsourcing and crowdfunding efforts in rare diseases research and how the upcoming initiatives for understanding disease biology including analyses of large number of genomes are also applicable to rare diseases.
Mukhi, Shamir N; Thibodeau, Melanie Laffin; Szijarto, Barbara
Background Surveillance of rare diseases in children is an important aspect of public health. Rare diseases affect thousands of children worldwide. The Canadian Paediatric Surveillance Program (CPSP) has been in existence since 1996, and provides an innovative means to undertake paediatric surveillance and increase awareness of childhood disorders that are high in disability, morbidity, mortality, and economic costs to society, despite their low frequency. Traditionally, CPSP used manual paper-based reporting on a monthly basis, which although had an impressive response rate, it had inherent longer processing times and costs associated with it. Objectives To provide an overview and evaluate an innovative web-based system that enables seamless reporting from participants across the country providing a quick, reliable and simple mechanism for the participants to submit data while yielding better data quality, timeliness and increased efficiencies. Methods In 2011, a proprietary electronic CPSP (eCPSP) system was developed to provide a simple, quick and reliable reporting environment for participants. It supports both the electronic and hardcopy reporting. The analysis presented in this paper was conducted based on usage data of this system. Results The response rates of the new eCPSP were found to be very favorable with adjusted rate of 80%, which equals the baseline. Approximately 50% of online participants report the first day they receive the notification e-mail. The response time was also reduced considerably. Furthermore, there has been significant reduction in data handling related activities (by almost 70%) from estimated 690 hours per year. Finally, the number of cases reported that do not fit the study case criteria has fallen, likely because participants can now immediately access the case definition and protocol via the online system. This has reduced both staff and investigator time for case processing. Conclusion The eCPSP has modernized the CPSP program
Filocamo, Mirella; Baldo, Chiara; Goldwurm, Stefano; Renieri, Alessandra; Angelini, Corrado; Moggio, Maurizio; Mora, Marina; Merla, Giuseppe; Politano, Luisa; Garavaglia, Barbara; Casareto, Lorena; Bricarelli, Francesca Dagna
Several examples have always illustrated how access to large numbers of biospecimens and associated data plays a pivotal role in the identification of disease genes and the development of pharmaceuticals. Hence, allowing researchers to access to significant numbers of quality samples and data, genetic biobanks are a powerful tool in basic, translational and clinical research into rare diseases. Recently demand for well-annotated and properly-preserved specimens is growing at a high rate, and is expected to grow for years to come. The best effective solution to this issue is to enhance the potentialities of well-managed biobanks by building a network.Here we report a 5-year experience of the Telethon Network of Genetic Biobanks (TNGB), a non-profit association of Italian repositories created in 2008 to form a virtually unique catalogue of biospecimens and associated data, which presently lists more than 750 rare genetic defects. The process of TNGB harmonisation has been mainly achieved through the adoption of a unique, centrally coordinated, IT infrastructure, which has enabled (i) standardisation of all the TNGB procedures and activities; (ii) creation of an updated TNGB online catalogue, based on minimal data set and controlled terminologies; (iii) sample access policy managed via a shared request control panel at web portal. TNGB has been engaged in disseminating information on its services into both scientific/biomedical - national and international - contexts, as well as associations of patients and families. Indeed, during the last 5-years national and international scientists extensively used the TNGB with different purposes resulting in more than 250 scientific publications. In addition, since its inception the TNGB is an associated member of the Biobanking and Biomolecular Resources Research Infrastructure and recently joined the EuroBioBank network. Moreover, the involvement of patients and families, leading to the formalization of various agreements
Langwińska-Wośko, Ewa; Litwin, Tomasz; Dzieżyc, Karolina; Członkowska, Anna
The presence of Kayser-Fleischer ring in patients with Wilson's disease (WD) is well documented and included in diagnostic algorithms; however, data about the occurrence of the second postulated ophthalmological sign of WD, sunflower cataract (SC), are limited and even conflicting. The aim of our study was to verify the occurrence of SC in WD. From January 2010 to May 2015, 81 consecutive, newly diagnosed WD patients underwent detailed ophthalmological examinations, including slit lamp examination with special attention to lens transparency, to verify the presence of SC in WD-naive patients. SC was detected in only one (1.2 %) of the examined WD patients, did not impact visual acuity; moreover, completely disappeared following a year of treatment for WD. SC may be a very rare and reversible ophthalmological manifestation of WD that is observed seldom and only at the time of WD diagnosis. We postulate that a finding of SC in WD patients is an interesting finding that may occur in the course of WD, but it is not a pathognomonic sign of WD.
Everton Nunes da Silva
Full Text Available This study analyzes the available evidence on the adequacy of economic evaluation for decision-making on the incorporation or exclusion of technologies for rare diseases. The authors conducted a structured literature review in MEDLINE via PubMed, CRD, LILACS, SciELO, and Google Scholar (gray literature. Economic evaluation studies had their origins in Welfare Economics, in which individuals maximize their utilities based on allocative efficiency. There is no widely accepted criterion in the literature to weigh the expected utilities, in the sense of assigning more weight to individuals with greater health needs. Thus, economic evaluation studies do not usually weigh utilities asymmetrically (that is, everyone is treated equally, which in Brazil is also a Constitutional principle. Healthcare systems have ratified the use of economic evaluation as the main tool to assist decision-making. However, this approach does not rule out the use of other methodologies to complement cost-effectiveness studies, such as Person Trade-Off and Rule of Rescue.
Pérez-Arellano, Isabel; Carmona-Álvarez, Francisco; Martínez, Ana I; Rodríguez-Díaz, Jesús; Cervera, Javier
Pyrroline-5-carboxylate synthase (P5CS) is a bifunctional enzyme that exhibits glutamate kinase (GK) and γ-glutamyl phosphate reductase (GPR) activities. The enzyme is highly relevant in humans because it belongs to a combined route for the interconversion of glutamate, ornithine and proline. The deficiency of P5CS activity in humans is associated with a rare, inherited metabolic disease. It is well established that some bacteria and plants accumulate proline in response to osmotic stress. The alignment of P5CSs from different species and analysis of the solved structures of GK and GPR reveal high sequence and structural conservation. The information acquired from different mutant enzymes with increased osmotolerant properties, together with the position of the insertion found in the longer human isoform, permit the delimitation of the regulatory site of GK and P5CS and the proposal of a model of P5CS architecture. Additionally, the GK moiety of the human enzyme has been modeled and the known clinical mutations and polymorphisms have been mapped. PMID:20091669
Full Text Available Adult onset Still’s disease (AOSD is a rare inflammatory disorder of unknown etiology that usually affects young adults. Very few patients older than 70-year-old have been reported. Clinical features include quotidian fevers, arthralgias, arthritis, pharyngitis, lymphadenopathy and an evanescent rash. AOSD should be considered in the differential diagnosis of fever of unknown origin. Early diagnosis is often difficult since it is a diagnosis of exclusion and the presence of infectious, neoplastic and autoimmune conditions needs to be ruled out before the diagnosis is made. No specific laboratory tests are available to aid in the diagnosis of AOSD. As a result, a set of diagnostic criteria that define the clinical features of this condition, termed the Yamaguchi criteria, have been most commonly used to establish the diagnosis. We describe the case of a 72-year-old Caucasian male with past medical history significant for generalized anxiety disorder, depression, BPH, and hypertriglyceridemia, who presented to a tertiary institution complaining of profound generalized weakness and weight loss that started three weeks prior to presentation. Initial laboratory studies showed leukocytosis, elevated ESR, CRP, ferritin and liver dysfunction. Cultures, ANA and rheumatoid factor studies were negative. The patient underwent further extensive workup that excluded the presence of infectious, neoplastic and autoimmune disorders and was subsequently diagnosed with AOSD and new onset diabetes mellitus. For the management of AOSD he was started on prednisone with significant improvement in markers of inflammation, symptoms and level of function.
Krabbenborg, Lotte; Vissers, L E L M; Schieving, J; Kleefstra, T; Kamsteeg, E J; Veltman, J A; Willemsen, M A; Van der Burg, S
The use of whole exome sequencing (WES) for diagnostics of children with rare genetic diseases raises questions about best practices in genetic counselling. While a lot of attention is now given to pre-test counselling procedures for WES, little is known about how parents experience the (positive, negative, or inconclusive) WES results in daily life. To fill this knowledge gap, data were gathered through in-depth interviews with parents of 15 children who underwent WES analysis. WES test results, like results from other genetic tests, evoked relief as well as worries, irrespective of the type of result. Advantages of obtaining a conclusive diagnosis included becoming more accepting towards the situation, being enabled to attune care to the needs of the child, and better coping with feelings of guilt. Disadvantages experienced included a loss of hope for recovery, and a loss by parents of their social network of peers and the effort necessary to re-establish that social network. While parents with conclusive diagnoses were able to re-establish a peer community with the help of social media, parents receiving a possible diagnosis experienced hurdles in seeking peer support, as peers still needed to be identified. These types of psychosocial effects of WES test results for parents are important to take into account for the development of successful genetic counselling strategies.
Full Text Available Squamous cell carcinoma (SCC of the endometrium, whether primary or secondary to cervical cancer, is a rare entity. Primary endometrial squamous cell carcinoma in situ is even more uncommon; it usually occurs in postmenopausal women and has a strong association with pyometra. We report a 60-year-old multiparous postmenopausal woman who presented to the Hakeem Abdul Hameed Centenary Hospital, New Delhi, India, in May 2014 with a lower abdominal swelling corresponding in size to a pregnancy of 26 gestational weeks and vaginal discharge of one year’s duration. A total abdominal hysterectomy with a bilateral salpingooophorectomy was performed, which revealed an enlarged uterus with pyometra. Histopathology showed that the entire endometrial lining had been replaced with malignant squamous cells without invasion of the myometrium. Immunohistochemistry revealed that the tumour cells were positive for p63 with a high Ki-67 labelling index. No adjuvant therapy was required and the patient was disease-free at a seven-month follow-up.
Maffei, Pietro; Munno, Vincenzo; Marshall, Jan D; Scandellari, Cesare; Sicolo, Nicola
The Alström syndrome is a rare, autosomal recessive disorder characterized by retinal degeneration, obesity, progressive hearing impairment, non-insulin-dependent diabetes mellitus and kidney and heart failure. Mental retardation is absent and the extremities are normal. The Alström syndrome gene located on chromosome 2, has been recently identified. The Alström syndrome involves multiple organ systems with a complex interaction between pathways. Phenotypic expression varies considerably, even within sibships. Manifestations observed in some, but not all, Alström syndrome patients include acanthosis nigricans, alopecia, short stature, scoliosis, kyphosis, hyperostosis frontalis interna, muscle dystonia, advanced bone age and subcapsular cataract. Other metabolic and endocrinological abnormalities have been described: hypothyroidism, hypogonadism, diabetes insipidus, growth hormone deficiency, hyperuricemia and hyperlipidemia. In the final stages of the disease, affected individuals exhibit progressive chronic nephropathy with eventual kidney failure. The most frequent causes of death include hepatic dysfunction and congestive heart failure secondary to dilated cardiomyopathy. We have summarized our personal clinical data and the information from the scientific literature on the topic in order to provide an up-to-date review on the Alström syndrome.
Badyal, Rama Kumari; Sachdeva, Man Updesh Singh; Varma, Neelam; Thapa, Babu Ram
An association between severe aplastic anemia and other autoimmune diseases is rare and has been described in adults for eosinophilic fasciitis, thymomas, systemic lupus erythematosus, and thyroid disorders. Herein we report a patient with celiac disease who was not strictly following a gluten-free diet and presented with progressive pallor, fever, and weakness of 1 month's duration. On investigation, he had pancytopenia, which on subsequent evaluation revealed aplastic anemia. An association between aplastic anemia and celiac disease has rarely been reported. To the best of author's knowledge, only 1 pediatric case of celiac disease associated with aplastic anemia has been published. This is the second report to suggest such an association in children.
Smith, Michael G; Royer, Julie; Mann, Joshua R; McDermott, Suzanne
Administrative records from insurance and hospital discharge data sources are important public health tools to conduct passive surveillance of disease in populations. Identifying rare but catastrophic conditions is a challenge since approaches for maximizing valid case detection are not firmly established. The purpose of our study was to explore a number of algorithms in which International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes and other administrative variables could be used to identify cases of muscular dystrophy (MD). We used active surveillance to identify possible cases of MD in medical practices in neurology, genetics, and orthopedics in 5 urban South Carolina counties and to identify the cases that had diagnostic support (ie, true cases). We then developed an algorithm to identify cases based on a combination of ICD-9-CM codes and administrative variables from a public (Medicaid) and private insurer claims-based system and a statewide hospital discharge dataset (passive surveillance). Cases of all types of MD and those with Duchenne or Becker MD (DBMD) that were common to both surveillance systems were examined to identify the most specific administrative variables for ascertainment of true cases. Passive statewide surveillance identified 3235 possible cases with MD in the state, and active surveillance identified 2057 possible cases in 5 actively surveilled counties that included 2 large metropolitan areas where many people seek medical care. There were 537 common cases found in both the active and passive systems, and 260 (48.4%) were confirmed by active surveillance to be true cases. Of the 260 confirmed cases, 70 (26.9%) were recorded as DBMD. Accuracy of finding a true case in a passive surveillance system was improved substantially when specific diagnosis codes, number of times a code was used, age of the patient, and specialty provider variables were used.
McKinnon, Allison; Black, Amanda Y; Lortie, Karine; Fleming, Nathalie A
Pelvic inflammatory disease (PID) is a polymicrobial infection that typically occurs in sexually active females. PID is rare in premenarchal and/or noncoital young women; however, there are case reports of PID occurring in virginal females. We present the first reported case of PID associated with F. nucleatum. In this unusual case of PID in an adolescent, the responsible organism may have originated from the patient's oral cavity. A 13-year-old noncoital Caucasian female presented to a tertiary children's hospital with fever and acute abdominal/pelvic pain. She had experienced a perforated appendix 14 months prior, which was treated by laparoscopy. Postoperatively, she experienced intermittent episodes of recurrent abdominal pain. During this presentation, the physical examination and ultrasound findings were suspicious for an ovarian torsion. She was taken to the operating room where she had an examination under anesthesia and a diagnostic laparoscopy. Findings at the time of laparoscopy were in keeping with a diagnosis of pelvic inflammatory disease. Oral and pelvic fluid cultures were positive for F. nucleatum. She was subsequently treated with antibiotics and her symptoms resolved. This case highlights the importance of including PID in the differential diagnosis of noncoital adolescent females presenting with an acute abdomen. Although most Fusobacteria infections are periodontal in nature, translocated infections to the pelvis may have long-term implications for reproductive health. This case also highlights the importance of the role of diagnostic laparoscopy in young women who have persistent pain following previous surgery due to the potential of missed pathology or subclinical infection. Copyright © 2013 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.
Robinson, Sandy W; Brantley, Kelly; Liow, Christine; Teagarden, J Russell
Patients with rare diseases often face significant health care access challenges, particularly since the number of available treatment options for rare diseases is limited. The implementation of health insurance exchanges promises improved access to health care. However, when purchasing a plan, patients with rare diseases need to consider multiple factors, such as insurance premium, access to providers, coverage of a specific medication or treatment, tier placement of drug, and out-of-pocket costs. To provide an early snapshot of the exchange plan landscape from the perspective of patients with select rare diseases by evaluating the degree of access to medications in a subset of exchange plans based on coverage, tier placement, associated cost sharing, and utilization management (UM) applied. The selection of drugs for this analysis began by identifying rare diseases with FDA-approved treatment options using the National Institutes of Health Office of Rare Diseases' webpage and further identification of a subset of drugs based on select criteria to ensure a varied sample, including the characteristics and prevalence of the condition. The medications were categorized based on whether alternative therapies have FDA approval for the same indication and whether there are comparators based on class or therapeutic area. The list was narrowed to 11 medications across 7 diseases, and the analysis was based on how these drugs are listed in exchange plan outpatient pharmacy benefit formularies. This analysis focused on 84 plans in 15 states with the highest expected exchange enrollment and included a variety of plan types to ensure that variability in the marketplace was represented. To best approximate plans that will have the greatest enrollment, the analysis focused on silver and bronze plan formularies because consumers in this market are expected to be sensitive to premiums. Data on drug coverage, tier placement, cost, and UM were collected from these plans
Berisha, Blerim; Krasniqi, Xhevdet; Thaqi, Agim; Gashi, Masar; Ko?inaj, Dardan
Background Single ventricle, bicuspid aortic valve and interatrial wall aneurysm in adulthood are a rare and unique case in medical literature. This presented case with congenital heart disease has never been treated surgically and clinical consequences seriously presented in adulthood. Case presentation A 27 year old man with complex congenital heart disease presented. At the age of six, the single ventricle was ultrasonographly diagnosed, but at age 27 clinical consequences started to be se...
Musters, Anne; Assaf, Amira; Gerlag, Danielle M; Tak, Paul P; Tas, Sander W
Biologics have revolutionized the field of clinical immunology and proven to be both effective and safe in common immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, inflammatory bowel diseases, and various hematological disorders. However, in patients with rare, severe IMIDs failing on standard therapies, it is virtually impossible to conduct randomized controlled trials. Therefore, biologics are usually prescribed off-label in these often severely ill patients. Unfortunately, off-label prescription is sometimes hampered in these diseases due to a lack of reimbursement that is often based on a presumed lack of evidence for effectiveness. In the present article, we will discuss that off-label prescription of biologics can be a good way to discover new treatments for rare diseases. This will be illustrated using a case of multicentric Castleman's disease, an immune-mediated lymphoproliferative disorder, in which off-label tocilizumab (humanized anti-IL-6 receptor blocking antibody) treatment resulted in remarkable clinical improvement. Furthermore, we will give recommendations for monitoring efficacy and safety of biologic treatment in rare IMIDs, including the use of registries. In conclusion, we put forward that innovative treatments for rare IMIDs can be discovered via off-label prescription of biologicals, provided that this is based on rational arguments including knowledge of the pathophysiology of the disease.
Annemans, Lieven; Aymé, Ségolène; Le Cam, Yann; Facey, Karen; Gunther, Penilla; Nicod, Elena; Reni, Michele; Roux, Jean-Louis; Schlander, Michael; Taylor, David; Tomino, Carlo; Torrent-Farnell, Josep; Upadhyaya, Sheela; Hutchings, Adam; Le Dez, Lugdivine
Rare diseases are an important public health issue with high unmet need. The introduction of the EU Regulation on orphan medicinal products (OMP) has been successful in stimulating investment in the research and development of OMPs. Despite this advancement, patients do not have universal access to these new medicines. There are many factors that affect OMP uptake, but one of the most important is the difficulty of making pricing and reimbursement (P&R) decisions in rare diseases. Until now, there has been little consensus on the most appropriate assessment criteria, perspective or appraisal process. This paper proposes nine principles to help improve the consistency of OMP P&R assessment in Europe and ensure that value assessment, pricing and funding processes reflect the specificities of rare diseases and contribute to both the sustainability of healthcare systems and the sustainability of innovation in this field. These recommendations are the output of the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL), a collaboration between rare disease experts, patient representatives, academics, health technology assessment (HTA) practitioners, politicians and industry representatives. ORPH-VAL reached its recommendations through careful consideration of existing OMP P&R literature and through a wide consultation with expert stakeholders, including payers, regulators and patients. The principles cover four areas: OMP decision criteria, OMP decision process, OMP sustainable funding systems and European co-ordination. This paper also presents a guide to the core elements of value relevant to OMPs that should be consistently considered in all OMP appraisals. The principles outlined in this paper may be helpful in drawing together an emerging consensus on this topic and identifying areas where consistency in payer approach could be achievable and beneficial. All stakeholders have an obligation to work together to ensure
Full Text Available Abstract Background Calls have been made for governments to adopt a cohesive approach to rare diseases through the development of national plans. At present, Australia does not have a national plan for rare diseases. To progress such a plan an inaugural Australian Rare Diseases Symposium was held in Western Australia in April 2011. This paper describes the key issues identified by symposium attendees for the development of a national plan, compares these to the content of EUROPLAN and national plans elsewhere and discusses how the outcomes might be integrated for national planning. Methods The symposium was comprised of a series of plenary sessions followed by workshops. The topics covered were; 1 Development of national plans for rare diseases; 2 Patient empowerment; 3 Patient care, support and management; 4 Research and translation; 5 Networks, partnerships and collaboration. All stakeholders within the rare diseases community were invited to participate, including: people affected by rare diseases such as patients, carers, and families; clinicians and allied health practitioners; social and disability services; researchers; patient support groups; industry (e.g. pharmaceutical, biotechnology and medical device companies; regulators and policy-makers. Results All of these stakeholder groups were represented at the symposium. Workshop participants indicated the need for a national plan, a national peak body, a standard definition of ‘rare diseases’, education campaigns, lobbying of government, research infrastructure, streamlined whole-of-lifetime service provision, case co-ordination, early diagnosis, support for health professionals and dedicated funding. Conclusions These findings are consistent with frameworks and initiatives being undertaken internationally (such as EUROPLAN, and with national plans in other countries. This implies that the development of an Australian national plan could plausibly draw on frameworks for plan
This feature looks at the challenges for information literacy in rare and orphan diseases. In particular, it focuses on the information difficulties faced by those living with a rare condition or awaiting a diagnosis, and also those of the health professionals in charge of their care. The feature also highlights some of the key issues that library and information professionals need to be aware of when providing information support in such circumstances. © 2014 The author. Health Information and Libraries Journal © 2014 Health Libraries Group.
Cacace, Rita; Van den Bossche, Tobi; Engelborghs, Sebastiaan; Geerts, Nathalie; Laureys, Annelies; Dillen, Lubina; Graff, Caroline; Thonberg, Håkan; Chiang, Huei-Hsin; Pastor, Pau; Ortega-Cubero, Sara; Pastor, Maria A; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Benussi, Luisa; Ghidoni, Roberta; Binetti, Giuliano; Nacmias, Benedetta; Sorbi, Sandro; Sanchez-Valle, Raquel; Lladó, Albert; Gelpi, Ellen; Almeida, Maria Rosário; Santana, Isabel; Tsolaki, Magda; Koutroumani, Maria; Clarimon, Jordi; Lleó, Alberto; Fortea, Juan; de Mendonça, Alexandre; Martins, Madalena; Borroni, Barbara; Padovani, Alessandro; Matej, Radoslav; Rohan, Zdenek; Vandenbulcke, Mathieu; Vandenberghe, Rik; De Deyn, Peter P; Cras, Patrick; van der Zee, Julie; Sleegers, Kristel; Van Broeckhoven, Christine
Rare variants in the phospholipase D3 gene (PLD3) were associated with increased risk for late-onset Alzheimer disease (LOAD). We identified a missense mutation in PLD3 in whole-genome sequence data of a patient with autopsy confirmed Alzheimer disease (AD) and onset age of 50 years. Subsequently, we sequenced PLD3 in a Belgian early-onset Alzheimer disease (EOAD) patient (N = 261) and control (N = 319) cohort, as well as in European EOAD patients (N = 946) and control individuals (N = 1,209) ascertained in different European countries. Overall, we identified 22 rare variants with a minor allele frequency <1%, 20 missense and two splicing mutations. Burden analysis did not provide significant evidence for an enrichment of rare PLD3 variants in EOAD patients in any of the patient/control cohorts. Also, meta-analysis of the PLD3 data, including a published dataset of a German EOAD cohort, was not significant (P = 0.43; OR = 1.53, 95% CI 0.60-3.31). Consequently, our data do not support a role for PLD3 rare variants in the genetic etiology of EOAD in European EOAD patients. Our data corroborate the negative replication data obtained in LOAD studies and therefore a genetic role of PLD3 in AD remains to be demonstrated.
Pipaliya, Nirav; Rathi, Chetan; Parikh, Pathik; Patel, Ruchir; Ingle, Meghraj; Sawant, Prabha
Intraductal papillary mucinous neoplasm (IPMN) accounts for 20-50% of all cystic neoplasms of the pancreas. Rarely, IPMN, whether benign or malignant, can fistulize into adjacent organs like duodenum, stomach or common bile duct. IPMN can be associated with other diseases like Peutz-Jeghers syndrome and familial adenomatous polyposis. Association with adult polycystic kidney disease (ADPKD) is extremely rare. We report a case of a 60-year-old male with a large IPMN in the head of the pancreas diagnosed by magnetic resonance imaging, endoscopic ultrasound and cyst fluid analysis. It was complicated by fistula formation into the second part of the duodenum. Patient was simultaneously having adult polycystic kidney disease. There is only one case report of uncomplicated IPMN with ADPKD in the literature so far. And even rarer, there is no any case report of fistulizing IPMN with ADPKD reported so far, to the best of our knowledge. PMID:27785296
This review aims to provide guidance on emerging concepts and policy related to European reference networks (ERNs) for rare diseases (RDs) and the development and management of RD patient registries. A major problem facing many RDs including rare renal disorders is that patients do not have a specialist centre that they can attend where clinicians, working as a multidisciplinary team, are experts in the particular disease. Furthermore, for most RDs, no single centre, and in many cases no single country, has sufficient numbers of patients and resources to fully understand the natural history or to conduct clinical and translational research. Therefore, the pooling of manpower and resources through the establishment of ERN and RD patient registries is a common and necessary area of collaboration. The concept of European networks for RDs dates back to the early 2000s and the Commission launch of a call for European pilot reference networks for RDs. These networks of expert centres have been brought together through the desire for further knowledge and innovation in RD areas. Networks demand a holistic approach and long-term vision with close collaboration between clinicians, diagnostic laboratories, scientists, patients and their families. The development of legal measures for ERNs is in progress at the Commission and these networks will be a shared responsibility of the Commission and member states. In the context of ERNs, an essential activity is the patient registries. Patient registries are organized databases where patient information, including demographic, medical and family history, are collected, stored and available for retrieval via standardized and secure methods. Patient registries are increasingly recognized as crucial tools for RD research for which international collaboration is absolutely essential to understand the pathogenesis of rare genotypes, achieve a unified collection of phenotypic data, foster natural history studies providing the foundation
Full Text Available Recently, whole-genome sequencing, especially exome sequencing, has successfully led to the identification of causal mutations for rare monogenic Mendelian diseases. However, it is unclear whether this approach can be generalized and effectively applied to other Mendelian diseases with high locus heterogeneity. Moreover, the current exome sequencing approach has limitations such as false positive and false negative rates of mutation detection due to sequencing errors and other artifacts, but the impact of these limitations on experimental design has not been systematically analyzed. To address these questions, we present a statistical modeling framework to calculate the power, the probability of identifying truly disease-causing genes, under various inheritance models and experimental conditions, providing guidance for both proper experimental design and data analysis. Based on our model, we found that the exome sequencing approach is well-powered for mutation detection in recessive, but not dominant, Mendelian diseases with high locus heterogeneity. A disease gene responsible for as low as 5% of the disease population can be readily identified by sequencing just 200 unrelated patients. Based on these results, for identifying rare Mendelian disease genes, we propose that a viable approach is to combine, sequence, and analyze patients with the same disease together, leveraging the statistical framework presented in this work.
Javier Fernando Camacho Tauta
Full Text Available La historia de esfuerzos tiene influencia sobre el comportamiento y la resistencia de los suelos. De particular interés es la condición anisotrópica de esfuerzos en que se presentan la mayoría de los suelos en condiciones naturales. Esta condición produce una disposición de las partículas que hace que las propiedades mecánicas tales como la rigidez inical o la resistencia al corte se vean afectadas. Se desarrollaron ensayos de laboratorio para estudiar de qué forma se pueden relacionar las condiciones de anisotropía inducida por esfuerzos, sobre los parámetros de resistencia en arenas. Se utilizó arena limpia y se controló cuidadosamente la ditribución granulométrica y la densidad relativa de cada espécimen, el cual se sometió a una combinación preestablecida de esfuerzos bajo condiciones drenadas. Finalmente cada probeta fue llevada a la falla para obtener los parámetros de resistencia al corte. Los resultados obtenidos muestran variaciones hasta del 10% en el ángulo de fricción interna, dependiendo de la densidad relativa del material y se observaron efectos negativos, especialmente en arenas mal gradadas de densidad relativa media.
Shimizu, Reiko; Ogata, Katsuhisa; Tamaura, Akemi; Kimura, En; Ohata, Maki; Takeshita, Eri; Nakamura, Harumasa; Takeda, Shin'ichi; Komaki, Hirofumi
Duchenne muscular dystrophy (DMD) is the most commonly inherited neuromuscular disease. Therapeutic agents for the treatment of rare disease, namely "orphan drugs", have recently drawn the attention of researchers and pharmaceutical companies. To ensure the successful conduction of clinical trials to evaluate novel treatments for patients with rare diseases, an appropriate infrastructure is needed. One of the effective solutions for the lack of infrastructure is to establish a network of rare diseases. To accomplish the conduction of clinical trials in Japan, the Muscular dystrophy clinical trial network (MDCTN) was established by the clinical research group for muscular dystrophy, including the National Center of Neurology and Psychiatry, as well as national and university hospitals, all which have a long-standing history of research cooperation. Thirty-one medical institutions (17 national hospital organizations, 10 university hospitals, 1 national center, 2 public hospitals, and 1 private hospital) belong to this network and collaborate to facilitate clinical trials. The Care and Treatment Site Registry (CTSR) calculates and reports the proportion of patients with neuromuscular diseases in the cooperating sites. In total, there are 5,589 patients with neuromuscular diseases in Japan and the proportion of patients with each disease is as follows: DMD, 29 %; myotonic dystrophy type 1, 23 %; limb girdle muscular dystrophy, 11 %; Becker muscular dystrophy, 10 %. We work jointly to share updated health care information and standardized evaluations of clinical outcomes as well. The collaboration with the patient registry (CTSR), allows the MDCTN to recruit DMD participants with specific mutations and conditions, in a remarkably short period of time. Counting with a network that operates at a national level is important to address the corresponding national issues. Thus, our network will be able to contribute with international research activity, which can lead to
Mehmet Nuri Konya
CONCLUSION: With this report we would like to raise awareness about the possible association of persistent CF with this rare genetical disorder, Ritscher–Schinzel syndrome. It should be included in differential diagnosis of patients with persistent CF.
Conclusions: Pelvic osteosarcomas are rare neoplasms with aggressive growth patterns. Survival results are poor in view of advanced stage of presentation and difficult surgical approaches. The combined modality approach is needed to improve the results.
Full Text Available We report of an 18-year-old male who presented with an epileptiform disorder, features of hypocalcemia, and an extrapyramidal symptom in the form of choreoathetosis. On evaluation he had idiopathic hypoparathyroidism with extensive calcifications in the extrapyramidal system of the brain; basal ganglion, as well as in the cerebral cortex and cerebellum, which is a rare entity. We report the rare presentation of a common disorder, which requires to be considered in evaluating hypoparathyroidism.
Rabeharisoa, Vololona; Callon, Michel; Marques Filipe, Angela; Arriscado Nunes, Joao; Paterson, Florence; Vergnaud, Frédéric
International audience; This article investigates how the engagement of patients' organisations (POs) in research relates to the dynamics of their activism in the area of rare diseases. It traces back how certain concerned families and groups elaborated rareness as an issue of equity and social justice, gave shape to what we call a 'politics of numbers' for stating the fact of rare diseases as a major public health problem, and promoted patients' critical involvement in biomedical and therape...
Full Text Available Abstract Background Disease-specific quality of life (QoL measures have enhanced the capacity of outcome measures to evaluate subtle changes and differences between groups. However, when the specific disease is rare, the cohort of patients is small and international collaboration is often necessary to accomplish meaningful research. As many of the QoL measures have been developed in North American English, they require translation to ensure their usefulness in a multi-cultural and/or international society. Published guidelines provide formal methods to achieve cross-culturally comparable versions of a QoL tool. However, these guidelines describe a rigorous process that is not always feasible, particularly in rare disease groups. The objective of this manuscript is to describe the process that was developed to achieve accurate cross-cultural translations of a disease-specific QoL measure, to overcome the challenges of a small sample size, i.e. children with a rare disorder. Procedure A measurement study was conducted in the United Kingdom (UK, France, Germany and Uruguay, during which the validated measure was translated into the languages of the respective countries. Results This is a report of a modified, child-centric, cross-cultural translation and adaptation process in which culturally appropriate and methodologically valid translations of a disease-specific QoL measure, the Kids' ITP Tools (KIT, were performed in children with immune thrombocytopenic purpura (ITP. The KIT was translated from North American English into UK English, French, German, and Spanish. Conclusion This study was a successful international collaboration. The modified process through which culturally appropriate and methodologically valid translations of QoL measures may be achieved in a pediatric population with a relatively rare disorder is reported.
Verma, Pradhuman; Verma, Kanika Gupta; Verma, Dinesh; Patwardhan, Nitin
Brown tumors are erosive bony lesions caused by rapid osteoclastic activity and peritrabecular fibrosis due to primary or secondary hyperparathyroidism resulting in a local destructive phenomenon. The differential diagnosis based on histological examination is only presumptive. Clinical, radiological and laboratory data are necessary for definitive diagnosis. Here, we report a very rare case of brown tumor involving maxilla and mandible, which is the result of secondary hyperparathyroidism in 30-year-old female patient with chronic renal disease. PMID:25328310
Full Text Available Pocas áreas de la asistencia pediátrica son tan susceptibles de revisión en cuanto a las pautas de actuación, y de tan necesaria formación por parte del profesional, como la asistencia a un niño y a su familia con una enfermedad rara (ER, muy especialmente si se trata de un niño malformado. El impacto de por vida, que conllevan muchas ER, obliga a un seguimiento continuado del niño, centrado tanto en los aspectos evolutivos del mismo como en la adaptación de la familia al problema. Además de la triste realidad a la que se enfrentan, los padres frecuentemente deben tomar decisiones inmediatas sobre el tratamiento médico o quirúrgico de su hijo, o enfrentarse a una condición letal o incapacitante que les «roba» sus expectativas. Sólo una adecuada atención a cada uno de los múltiples problemas a los que se enfrentan estos niños y sus familias ayuda a minimizar el potencial handicap asociado a las ER. A pesar de la indudable complejidad que conlleva la profundización en este campo, el pediatra debe introducirse en el conocimiento de estas enfermedades con la finalidad de fundamentar su implicación en el diagnóstico y seguimiento de los pacientes. Su abstención ante esta responsabilidad repercutiría negativamente en la atención a estos enfermos, que deberá compartir con los especialistas correspondientes.Few areas of paediatric care are as susceptible to the revision of lines of action, and require such professional training, as the care of the child with a rare disease (RD and his/her family, especially if there are malformations. The lifelong impact, which many RDs entail, make continuous monitoring of the child compulsory, centred both on the evolutionary aspects of the RD and on the family’s adaptation to the problem. Besides the sad reality they confront, the parents must frequently make immediate decisions on medical or surgical treatment for their child, or face a lethal or disabling condition that "robs" them of
Toubiana, Laurent; Ugon, Adrien; Giavarini, Alessandra; Riquier, Jérémie; Charlet, Jean; Jeunemaitre, Xavier; Plouin, Pierre-François; Jaulent, Marie-Christine
The SIR-FMD project is a partnership between the Department of Genetics and Reference Centre for Rare Vascular Diseases at the Georges Pompidou European Hospital in Paris and the Medical Informatics and Knowledge Engineering Laboratory of Inserm. Its aim is to use an ontological approach to implement an information system for the French Fibromuscular Dysplasia Registry. The existing data was dispersed in numerous databases, which had been created independently. These databases have different structures and contain data of diverse quality. The project aims to provide generic solutions for the management of the communication of medical data. The secondary objective is to demonstrate the applicability of these generic solutions in the field of rare diseases (RD) in an operational context. The construction of the French FMD registry was a multistep process. A secure platform has been available since the beginning of November 2013. The medical records of 471 patients from the initial dataset provided by the HEGP-Paris, France have been included, and are accessible from a secure user account. Users are organized into a collaborative group, and can access patient groups. Each electronic patient record contains more than 2,200 items. The problem of semantic interoperability has become one of the major challenges for the development of applications requiring the sharing and reuse of data. The information system component of the SIR-FMD project has a direct impact on the standardisation of coding of rare diseases and thereby contributes to the development of e-Health.
Full Text Available Abstract Background A rare disease is a pattern of symptoms that afflicts less than five in 10,000 patients. However, as about 6,000 different rare disease patterns exist, they still have significant epidemiological relevance. We focus on rare diseases that affect multiple organs and thus demand that multidisciplinary healthcare professionals (HCPs work together. In this context, standardized healthcare processes and concepts are mainly lacking, and a deficit of knowledge induces uncertainty and ambiguity. As such, individualized solutions for each patient are needed. This necessitates an intensive level of innovative individual behavior and thus, adequate idea generation. The final implementation of new healthcare concepts requires the integration of the expertise of all healthcare team members, including that of the patients. Therefore, knowledge sharing between HCPs and shared decision making between HCPs and patients are important. The objective of this study is to assess the contribution of shared communication and decision-making processes in patient-centered healthcare teams to the generation of innovative concepts and consequently to improvements in patient satisfaction. Methods A theoretical framework covering interaction processes and explorative outcomes, and using patient satisfaction as a measure for operational performance, was developed based on healthcare management, innovation, and social science literature. This theoretical framework forms the basis for a three-phase, mixed-method study. Exploratory phase I will first involve collecting qualitative data to detect central interaction barriers within healthcare teams. The results are related back to theory, and testable hypotheses will be derived. Phase II then comprises the testing of hypotheses through a quantitative survey of patients and their HCPs in six different rare disease patterns. For each of the six diseases, the sample should comprise an average of 30 patients with
van Karnebeek Clara D M
Full Text Available Abstract Background Intellectual disability (ID is a devastating and frequent condition, affecting 2-3% of the population worldwide. Early recognition of treatable underlying conditions drastically improves health outcomes and decreases burdens to patients, families and society. Our systematic literature review identified 81 such inborn errors of metabolism, which present with ID as a prominent feature and are amenable to causal therapy. The WebAPP translates this knowledge of rare diseases into a diagnostic tool and information portal. Methods & results Freely available as a WebAPP via http://www.treatable-id.org and end 2012 via the APP store, this diagnostic tool is designed for all specialists evaluating children with global delay / ID and laboratory scientists. Information on the 81 diseases is presented in different ways with search functions: 15 biochemical categories, neurologic and non-neurologic signs & symptoms, diagnostic investigations (metabolic screening tests in blood and urine identify 65% of all IEM, therapies & effects on primary (IQ/developmental quotient and secondary outcomes, and available evidence For each rare condition a ‘disease page’ serves as an information portal with online access to specific genetics, biochemistry, phenotype, diagnostic tests and therapeutic options. As new knowledge and evidence is gained from expert input and PubMed searches this tool will be continually updated. The WebAPP is an integral part of a protocol prioritizing treatability in the work-up of every child with global delay / ID. A 3-year funded study will enable an evaluation of its effectiveness. Conclusions For rare diseases, a field for which financial and scientific resources are particularly scarce, knowledge translation challenges are abundant. With this WebAPP technology is capitalized to raise awareness for rare treatable diseases and their common presenting clinical feature of ID, with the potential to improve health outcomes
Full Text Available Background. Spontaneous perforation of the extrahepatic biliary system is a rare presentation of gall stones. Very few cases of bile duct perforation have been reported in adults. It is rarely suspected or correctly diagnosed preoperatively. Case Presentation. A 66-year-old female presented at the surgical emergency with 3 days’ history of severe upper abdominal pain with distension and repeated episodes of vomiting, as she had evidence of generalized peritonitis and underwent an exploratory laparotomy. A single 0.5 cm × 0.5 cm free perforation was present on the anterolateral surface of the common bile duct at the junction of cystic duct. A cholecystectomy and the CBD exploration were performed. Conclusion. Spontaneous perforation of the extrahepatic bile duct is a rare but important presentation of gall stones in adults. Therefore, awareness of the clinical presentation, expert ultrasound examination, and surgery are important aspects in the management.
Berber, Ilhami; Erkurt, Mehmet Ali; Yetkin, Funda; Unlu, Serkan; Yilmaz, Sami; Bentli, Recep; Bazna, Sezai
Some infectious organisms may give rise to acute pancreatitis; brucellosis, however, extremely rarely leads to acute pancreatitis. A 40-year-old man was diagnosed with acute pancreatitis, the etiology of which was determined to be acute brucellosis. The patient was discharged without complications approximately 15 days after the initiation of trimethoprim-sulfamethoxazole and doxycycline treatment. Brucella infections may rarely be complicated by acute pancreatitis. Thus, brucellosis should be remembered in the etiology of acute pancreatitis in regions such as Turkey, where Brucella infections are endemic.
Marcela de Almeida-Menezes
Full Text Available Background: Celiac disease is described in association with several autoimmune diseases, but rarely with myasthenia gravis. Case Report: We describe the case of a 31-year-old white woman with celiac disease who presented manifestations related to a hyperactive immune system, including macroamylasemia, false-positive anti-HCV, positive antinuclear antibody, and Raynaud's phenomenon. The Introduction of a gluten-free diet (GFD resolved these features, but myasthenia gravis (MG symptoms unexpectedly occurred on that occasion. Discussion: The role of a GFD in the course of autoimmune diseases has been studied and improvement has been reported in many diseases. However, there is no consensus in the literature regarding the course of neurological disorders associated with celiac disease. In the present case, a GFD did not prevent the appearance of symptoms related to myasthenia gravis. There are few reports on the association of celiac disease with myasthenia gravis and therefore little is known about the course and time of onset of myasthenia in celiac patients. The present case increases the knowledge about this unusual autoimmune neurological disease associated with celiac disease.
Talsma, Melle; Kroos, MA; Visser, G; Kimpen, JLL; Niezen, KE
Myocarditis attributed to Epstein-Barr virus (EBV) as the sole cause is a rare manifestation. Myocarditis ascribed to EBV infection in combination with other factors has been reported in a few more cases. We report a child who experienced active EBV infection and later, at 19 months of age, received
Irina V Liskina
Full Text Available The article presents a rare case of pulmonary manifestation of seropositive protracted rheumatoid arthritis in the form of bronchocentric granulomatosis. The algorithm for diagnosis is described in details in the context of the known literature on pulmonary manifestations as a complication of rheumatoid arthritis and morphology of bronchocentric granulomatosis.
Talsma, Melle; Kroos, MA; Visser, G; Kimpen, JLL; Niezen, KE
Myocarditis attributed to Epstein-Barr virus (EBV) as the sole cause is a rare manifestation. Myocarditis ascribed to EBV infection in combination with other factors has been reported in a few more cases. We report a child who experienced active EBV infection and later, at 19 months of age, received
Conejos-Sánchez, Inmaculada; Cardoso, Isabel; Oteo-Vives, Marta; Romero-Sanz, Eduardo; Paul, Alison; Sauri, Amparo Ruiz; Morcillo, Miguel A; Saraiva, Maria J; Vicent, María J
The term amyloidosis describes neurological diseases where an abnormal protein is misfolded and accumulated as deposits in organs and tissues, known as amyloid, disrupting their normal function. In the most common familial amyloid polyneuropathy (FAP), transthyretin (TTR) displays this role primarily affecting the peripheral nervous system (PNS). Advanced stages of this inherited rare amyloidosis, present as fibril deposits that are responsible for disease progression. In order to stop disease progression, herein we designed an efficient family of nanoconjugates as fibril disrupters. These polymer conjugates are based on doxycycline (doxy), already in phase II trials for Alzheimer's disease, covalently linked to poly-l-glutamic acid (PGA). The conjugates were rationally designed, looking at drug loading and drug release rate by adequate linker design, always considering the physiological conditions at the molecular target site. Conjugation of doxycycline exhibited greater potential towards TTR fibril disaggregation in vitro compared to the parent drug. Exhaustive physico-chemical evaluation of these polymer-drug conjugates concluded that drug release was unnecessary for activity, highlighting the importance of an appropriate linker. Furthermore, biodistribution studies through optical imaging (OI) and the use of radiolabelled polymer-drug conjugates demonstrated conjugate safety profile and renal clearance route of the selected PGA-doxy candidate, settling the adequacy of our conjugate for future in vivo evaluation. Furthermore, preliminary studies in an FAP in vivo model at early stages of disease development showed non-organ toxicity evidences. This nanosized-system raises a promising treatment for advanced stages of this rare amyloidotic disease, and also presents a starting point for possible application within other amyloidosis-related diseases, such as Alzheimer's disease. Copyright © 2014 Elsevier B.V. All rights reserved.
Yu-Wai-Man, C; Petheram, K; Davidson, A W; Williams, T; Griffiths, P G
A case is described of motor neurone disease presenting with an ocular motor disorder characterised by saccadic intrusions, impaired horizontal and vertical saccades, and apraxia of eyelid opening. The occurrence of eye movement abnormalities in motor neurone disease is discussed.
Luis Suárez Flórez
Full Text Available Se llama la atención sobre la energía humana, su importancia como elemento de productividad y como principio ó quizás como fin de la actividad deportiva. Se estudia el máximo esfuerzo físico, así como también algunos conceptos acerca de la energía aeróbica y la energía anaeróbica.
Rubén Fernández García
Full Text Available En este estudio se evaluó el efecto de aplicar hipnosis para resistir esfuerzos máximos durante el mayor tiempo posible. Participaron en la investigación 24 deportistas juveniles y aficionados practicantes de ciclismo, con una edad media de 17,75 años (Sd 0,97, peso medio de 68 Kg (Sd 3,98, talla media de 178 cm (Sd 15,02 y un promedio de 5,75 años compitiendo (Sd 0,48. Estos se distribuyeron aleatoriamente en dos grupos denominados: hipnosis y control. La intervención con hipnosis consistió en la utilización de una breve técnica de relajación, fase de inducción hipnótica, fase de profundización, introducción de sugestión posthipnótica y fase de salida del estado hipnótico. Los resultados indicaron una relación estadísticamente significativa (p<0.05 en la variable resistencia al esfuerzo, analizada mediante 2 (16,78 y lambda (0.90, respecto al tipo de tratamiento. La resistencia al esfuerzo mejoraba a medida que se incrementaba el número de sesiones de intervención. Podemos concluir que la intervención con hipnosis ayudó a los deportistas a resistir durante más tiempo situaciones de máximo esfuerzo.
Kryukov, Gregory V.; Pennacchio, Len A.; Sunyaev, Shamil R.
The accumulation of mildly deleterious missense mutations inindividual human genomes has been proposed to be a genetic basis forcomplex diseases. The plausibility of this hypothesis depends onquantitative estimates of the prevalence of mildly deleterious de novomutations and polymorphic variants in humans and on the intensity ofselective pressure against them. We combined analysis of mutationscausing human Mendelian diseases, human-chimpanzee divergence andsystematic data on human SNPs and found that about 20 percent of newmissense mutations in humans result in a loss of function, while about 27percent are effectively neutral. Thus, more than half of new missensemutations have mildly deleterious effects. These mutations give rise tomany low frequency deleterious allelic variants in the human populationas evident from a new dataset of 37 genes sequenced in over 1,500individual human chromosomes. Surprisingly, up to 70 percent of lowfrequency missense alleles are mildly deleterious and associated with aheterozygous fitness loss in the range 0.001-0.003. Thus, the low allelefrequency of an amino acid variant can by itself serve as a predictor ofits functional significance. Several recent studies have reported asignificant excess of rare missense variants in disease populationscompared to controls in candidate genes or pathways. These studies wouldbe unlikely to work if most rare variants were neutral or if rarevariants were not a significant contributor to the genetic component ofphenotypic inheritance. Our results provide a justification for thesetypes of candidate gene (pathway) association studies and imply thatmutation-selection balance may be a feasible mechanism for evolution ofsome common diseases.
Full Text Available We report a rare case of tuberculosis (TB of base of the tongue following pulmonary TB. Patient presented to us with chief complaints of sore throat, dysphagia, and hoarseness of voice for 20 days. Examination with 90° telescope revealed ulcerative lesion in the base of the tongue on the left side of size 0.5 cm and another lesion in the left arytenoid and inter arytenoid area extending to the false vocal cord of the left side with undermined edges along with whitish slough at the center of the ulcer. Infection of the oral cavity with Mycobacterium tuberculosis is rare, however, it should be considered among the differential diagnosis of the lesions of the oral cavity. The biopsy is necessary to confirm the diagnosis.
Perić, Zinaida; Kardum-Skelin, Ika; Puskarić, Biljana Jelić; Letilović, Tomislav; Vrhovac, Radovan; Jaksić, Branimir
Gaucher's disease (GD) has variable presentations, but cardiac involvement is a generally uncommon clinical manifestation of the disease. In the past 25 years, the underlying genetic disorder in GD has been well characterized, with almost 300 mutations identified in the glucocerebrosidase gene (GBA). Nevertheless, clear genotype-phenotype correlations have been confirmed only for the most frequent mutations. We present a female patient, who was known to have aortic valve pathology from the age of 30. Despite medical follow up, at the age of 60 she presented with heart failure (NYHA III). At that time echocardiography showed severe fibrosed aortic valve stenosis. Valvuloplasty was planned, when thrombocytopenia, previously considered to be autoimmune, became severe. Anemia and leukopenia were also noted. Moderate splenomegaly and severe bone marrow infiltration were found on MRI. Bone marrow aspiration revealed typical Gaucher cells and the enzyme activity assay confirmed the diagnosis. DNA investigation showed that the patient is homozygous for the G377S mutation. To our knowledge, of all mutations identified so far, only homozygosity for the D409H mutation has been associated with cardiovascular valvular disease in patients with a rare type 3c GD. G377S, found in our patient, is a rare mutation, previously reported as a 'mild' mutation, because of the finding that homoallelic patients were essentialy asymptomatic or had mild disease. Our patient, also homozygous for G377S mutation, had a severe form of type 1 GD, with rare cardiac valve involvement, which is a previously unreported clinical presentation for this mutation. This case further proves that patients with the same genotypes can have different phenotypes, emphasizing the influence of other genetic and/or environmental factors.
George Peter; Hegde Narasimha
Leptospirosis is a zoonotic infection with higher incidence in tropics. Leptospirosis, is known for its variable manifestations, and is a clinical challenge for physicians in the tropics. Experienced clinicians, at times can mistake leptospirosis for non-medical conditions. A few reports of leptospirosis presenting as acalculous cholecystitis was found in review of literature. We intent to highlight acalculous cholecystitis as a rare but clinically significant presentation of leptospirosis.
Non-traumatic elbow pain is rarely seen in children and pre-adolescents. Osteochondral lesions may be the source of chronic elbow pain, swelling, and loss of motion in children or adolescents. Osteochondritis dissecans (OCD) is described as a lesion of subchondral bone resulting in separation of the articular cartilage and subchondral bone. It is found primarily in the knee, ankle, and elbow joints. Since osteochondrosis of the elbow primarily involves capitellum, few papers involving osteone...
Ashok S; Ankit; Aundhakar; Lekha; Umardand
It is a rare genetic disorder characterized by the absence of the radius bone in the forearm and a dramatically reduced platelet count. This syndrome may occur as a part of the 1q21.1 deletion syndrome. Symptoms of thrombocytopenia or a lowered platelet count leads to bruising and potentially life-threatening haemorrhage. Affected children who survive this period and do not have damaging haemorrhages in the brain usually have a normal life expectancy and normal intellectual develo...
Nguyen, M T; Charlebois, K
Whole-exome sequencing (WES) carries the potential to facilitate the identification of disease causing genes. This is particularly relevant concerning rare diseases, which proves particularly difficult for physicians to diagnose. However, the complexity of this technology renders its applicability onto the clinical setting uncertain. Our study thus aims to understand physicians' perspectives regarding the clinical utility of WES, particularly for providing a diagnosis for patients with rare diseases. Ten semi-structured interviews were conducted with physicians with experience and familiarity with WES, and the major themes that emerged from our interviews were (i) the relevance of WES in diagnosing patients with rare diseases (appropriateness); (ii) the cost-effectiveness of WES (accessibility), (iii) the practical issues related to the clinical implementation of WES (practicability); and (iv) ethical, legal and social issues (acceptability). Our study highlights how the clinical implementation of WES presents additional challenges where rare diseases are taken into consideration.
Xie, Peng; Huang, Jian-Min; Li, Huan-Li; Huang, Xiao-Jie; Wei, Ling-Ge
Camurati-Engelmann disease (i.e., progressive diaphyseal dysplasia) is an extremely rare autosomal dominant bone disorder. The most common clinical manifestations were chronic skeletal pain, waddling gait, muscular weakness. We described that a 27-year-old male with a 1-year history of intermittent tetany was referred for bone scintigraphy. The whole body bone scan images showed abnormal increased uptake of the tracer in the long bones of the upper and lower extremities as well as in the skull. Combined the family history, the findings of the images and the genetic study, the diagnosis of Camurati-Engelmann disease was confirmed. The patient responded well to the treatment of calcium gluconate. Bone scintigraphy would be helpful in the diagnosis and assessing the severity of Camurati-Engelmann disease.
Han, Harry J; Jain, Payal; Resnick, Adam C
Gain-of-function mutations in the Type I Bone Morphogenic Protein (BMP) receptor ACVR1 have been identified in two diseases: Fibrodysplasia Ossificans Progressiva (FOP), a rare autosomal dominant disorder characterized by genetically driven heterotopic ossification, and in 20-25% of Diffuse Intrinsic Pontine Gliomas (DIPGs), a pediatric brain tumor with no effective therapies and dismal median survival. While the ACVR1 mutation is causal for FOP, its role in DIPG tumor biology remains under active investigation. Here, we discuss cross-fertilization between the FOP and DIPG fields, focusing on the biological mechanisms and principles gleaned from FOP that can be applied to DIPG biology. We highlight our current knowledge of ACVR1 in both diseases, and then describe the growing opportunities and barriers to effectively investigate ACVR1 in DIPG. Importantly, learning from other seemingly unrelated diseases harboring similar mutations may uncover novel mechanisms or processes for future investigation. Copyright © 2017 Elsevier Inc. All rights reserved.
Yaman, Ayhan; Eminoğlu, Fatma T; Kendirli, Tanıl; Ödek, Çağlar; Ceylaner, Serdar; Kansu, Aydan; İnce, Elif; Deda, Gülhis
Niemann-Pick disease type C (NPC) is a fatal autosomal recessive lipid storage disease associated with impaired trafficking of unesterified cholesterol and glycolipids in lysosomes and late endosomes. This disease is commonly characterized by hepatosplenomegaly and severe progressive neurological dysfunction. There are two defective genes that cause this illness. One of these genes is NPC1 gene which is the cause of illness in 95% of the patients. The other gene is the rare type NPC2 which is the cause of illness in 5% of the patients. Patients with NPC2 usually present with respiratory distress in early infancy, which is rather unusual with NPC1. This article discusses about a patient who died at an early age from pulmonary involvement and who subsequently was found to have a novel homozygous mutation of NPC2 gene.
van de Warrenburg, Bart P; Schouten, Meyke I; de Bot, Susanne T; Vermeer, Sascha; Meijer, Rowdy; Pennings, Maartje; Gilissen, Christian; Willemsen, Michèl AAP; Scheffer, Hans; Kamsteeg, Erik-Jan
Cerebellar ataxia (CA) and hereditary spastic paraplegia (HSP) are two of the most prevalent motor disorders with extensive locus and allelic heterogeneity. We implemented clinical exome sequencing, followed by filtering data for a ‘movement disorders' gene panel, as a generic test to increase variant detection in 76 patients with these disorders. Segregation analysis or phenotypic re-evaluation was utilized to substantiate findings. Disease-causing variants were identified in 9 of 28 CA patients, and 8 of 48 HSP patients. In addition, possibly disease-causing variants were identified in 1 and 8 of the remaining CA and HSP patients, respectively. In 10 patients with CA, the total disease-causing or possibly disease-causing variants were detected in 8 different genes, whereas 16 HSP patients had such variants in 12 different genes. In the majority of cases, the identified variants were compatible with the patient phenotype. Interestingly, in some patients variants were identified in genes hitherto related to other movement disorders, such as TH variants in two siblings with HSP. In addition, rare disorders were uncovered, for example, a second case of HSP caused by a VCP variant. For some patients, exome sequencing results had implications for treatment, exemplified by the favorable L-DOPA treatment in a patient with HSP due to ATP13A2 variants (Parkinson type 9). Thus, clinical exome sequencing in this cohort of CA and HSP patients suggests broadening of disease spectra, revealed novel gene–disease associations, and uncovered unanticipated rare disorders. In addition, clinical exome sequencing results have shown their value in guiding practical patient management. PMID:27165006
Brown, Carl J.; Hussein Jaffer; Nasir Jaffer; Claude Burul; McLeod, Robin S.
Spinal epidural abscess is an uncommon but highly morbid illness. While it usually afflicts older, immunocompromised patients, this condition has been reported as a result of intestinal perforation in the setting of inflammatory bowel disease. Two cases of spinal epidural abscess in patients with inflammatory bowel disease are reported: one in a patient with Crohn’s disease and one in a patient with ulcerative colitis after restorative proctocolectomy.
Carl J Brown
Full Text Available Spinal epidural abscess is an uncommon but highly morbid illness. While it usually afflicts older, immunocompromised patients, this condition has been reported as a result of intestinal perforation in the setting of inflammatory bowel disease. Two cases of spinal epidural abscess in patients with inflammatory bowel disease are reported: one in a patient with Crohn’s disease and one in a patient with ulcerative colitis after restorative proctocolectomy.
Chica, Edwin; Latorre, Federico; Agudelo, Sergio
Introduccion: el proposito de este estudio fue analizar la distribucion de los esfuerzos entre tres alternativas de retencion de una protesis dental parcial fija de tres unidades, utilizando el metodo de elementos finitos (MEF). Metodos...
Qurratul Ann Warsi
Full Text Available Crohn’s disease is an inflammatory bowel disease (IBD, characterized by chronic intestinal inflammation that causes the loss of immune tolerance leading to bizarre inflammatory signals and disruption of mucosal barriers. Environmental triggers and interaction of genetic determinants also play an indispensible role. In this case report, we present a pre-pubertal girl with intermittent and refractory genital swelling. We emphasize that Crohn’s disease must be considered in the differential diagnosis of recurrent, non-tender, erythematous and edematous lesions of the genital area. We conclude with future directions for diagnosing and managing vulvar Crohn’s disease in pediatric population.
Alexandra F S Breitenkamp
Full Text Available Autism Spectrum Disorders (ASD are complex neurodevelopmental diseases clinically defined by dysfunction of social interaction. Dysregulation of cellular calcium homeostasis might be involved in ASD pathogenesis, and genes coding for the L-type calcium channel subunits CaV1.2 (CACNA1C and CaVβ2 (CACNB2 were recently identified as risk loci for psychiatric diseases. Here, we present three rare missense mutations of CACNB2 (G167S, S197F, and F240L found in ASD-affected families, two of them described here for the first time (G167S and F240L. All these mutations affect highly conserved regions while being absent in a sample of ethnically matched controls. We suggest the mutations to be of physiological relevance since they modulate whole-cell Ba2+ currents through calcium channels when expressed in a recombinant system (HEK-293 cells. Two mutations displayed significantly decelerated time-dependent inactivation as well as increased sensitivity of voltage-dependent inactivation. In contrast, the third mutation (F240L showed significantly accelerated time-dependent inactivation. By altering the kinetic parameters, the mutations are reminiscent of the CACNA1C mutation causing Timothy Syndrome, a Mendelian disease presenting with ASD. In conclusion, the results of our first-time biophysical characterization of these three rare CACNB2 missense mutations identified in ASD patients support the hypothesis that calcium channel dysfunction may contribute to autism.
Smith, Sean Robinson; Fu, Jack B
Paraneoplastic stiff person syndrome is a rare, but debilitating, manifestation of cancer, characterized by painful extremities, truncal and facial spasms. The resultant functional impairment may necessitate comprehensive rehabilitation and symptom management. This case series describes the acute inpatient rehabilitation courses of 2 patients at different tertiary care referral cancer rehabilitation programmes, including work-up and diagnosis, medical management of symptoms, and functional outcomes. Both patients had a reduction in symptom burden and an improvement in motor function as a result of multidisciplinary acute inpatient rehabilitation.
Full Text Available Alternaria alternata is one of the rarest fungi associated with paranasal sinusitis. Alternaria species are pigmented (also known as dematiaceous or phaeoid filamentous fungi, which are well-known soil saprophytes and plant pathogens that infrequently cause infection in humans mainly, cutaneous lesions. We present a case of osteomyelitis of maxilla caused by a rare fungus- A. alternata in a diabetic patient with poor glycemic control who was successfully treated with antifungal and surgical debridement over the period of 6 months.
Duclos, G; Eté, M; Bassez, C; Gainnier, M; Eon, B
We present the case of a 46-year-old patient without any past medical history, admitted to our ICU for cardiogenic shock complicating acute coronary syndrome. The blood tests found polycethemia, a polycethemia vera was suspected and confirmed by genetic analysis. Ischemic heart failure as an initial symptom of polycethemia vera and its treatment by arterial bleeding is a rare event that we describe in this article. Copyright © 2014 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.
Trynka, Gosia; Hunt, Karen A.; Bockett, Nicholas A.; Romanos, Jihane; Mistry, Vanisha; Szperl, Agata; Bakker, Sjoerd F.; Bardella, Maria Teresa; Bhaw-Rosun, Leena; Castillejo, Gemma; de la Concha, Emilio G.; de Almeida, Rodrigo Coutinho; Dias, Kerith-Rae M.; van Diemen, Cleo C.; Dubois, Patrick C. A.; Duerr, Richard H.; Edkins, Sarah; Franke, Lude; Fransen, Karin; Gutierrez, Javier; Heap, Graham A. R.; Hrdlickova, Barbara; Hunt, Sarah; Plaza Izurieta, Leticia; Izzo, Valentina; Joosten, Leo A. B.; Langford, Cordelia; Mazzilli, Maria Cristina; Mein, Charles A.; Midah, Vandana; Mitrovic, Mitja; Mora, Barbara; Morelli, Marinita; Nutland, Sarah; Nunez, Concepcion; Onengut-Gumuscu, Suna; Pearce, Kerra; Platteel, Mathieu; Polanco, Isabel; Potter, Simon; Ribes-Koninckx, Carmen; Ricano-Ponce, Isis; Rich, Stephen S.; Rybak, Anna; Luis Santiago, Jose; Senapati, Sabyasachi; Sood, Ajit; Szajewska, Hania; Troncone, Riccardo; Varade, Jezabel; Wallace, Chris; Wolters, Victorien M.; Zhernakova, Alexandra; Thelma, B. K.; Cukrowska, Bozena; Urcelay, Elena; Ramon Bilbao, Jose; Mearin, M. Luisa; Barisani, Donatella; Barrett, Jeffrey C.; Plagnol, Vincent; Deloukas, Panos; Wijmenga, Cisca; van Heel, David A.
Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 1
Trynka, G.; Hunt, K.A.; Bockett, N.A.; Romanos, J.; Mistry, V.; Szperl, A.; Bakker, S.F.; Bardella, M.T.; Bhaw-Rosun, L.; Castillejo, G.; Concha, E. de la; Almeida, R.C. de; Dias, K.R.; Diemen, C.C. van; Dubois, P.C.; Duerr, R.H.; Edkins, S.; Franke, L.; Fransen, K.; Gutierrez, J.; Heap, G.A.; Hrdlickova, B.; Hunt, S.; Izurieta, L.P.; Izzo, V.; Joosten, L.A.B.; Langford, C.; Mazzilli, M.C.; Mein, C.A.; Midah, V.; Mitrovic, M.; Mora, B.; Morelli, M.; Nutland, S.; Nunez, C.; Onengut-Gumuscu, S.; Pearce, K.; Platteel, M.; Polanco, I.; Potter, S.; Ribes-Koninckx, C.; Ricano-Ponce, I.; Rich, S.S.; Rybak, A.; Santiago, J.L.; Senapati, S.; Sood, A.; Szajewska, H.; Troncone, R.; Varade, J.; Wallace, C.; Wolters, V.M.; Zhernakova, A.; Thelma, B.K.; Cukrowska, B.; Urcelay, E.; Bilbao, J.R.; Mearin, M.L.; Barisani, D.; Barrett, J.C.; Plagnol, V.; Deloukas, P.; Wijmenga, C.; Heel, D.A. van
Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 1
Psoma, Elizabeth; Nikolaidou, Olga; Stavrogianni, Thomai; Mavromati, Areti; Lytras, Konstantinos; Xirou, Persefoni; Koumbanaki, Melanie; Panagiotopoulou, Dimitra
Neuroendocrine carcinomas are malignancies deriving from neuroendocrine cells existing in various sites of the body, most commonly in the lungs and gastrointestinal tract. Primary neuroendocrine carcinomas of the breast are extremely rare, and their diagnosis is confirmed by positive neuroendocrine markers. We describe a case of a 46-year-old woman with a palpable mass in her left breast for the previous 3 months. The tumor was resected and a primary large-cell neuroendocrine tumor of the breast was confirmed by histopathologic examination. Paget disease of the nipple was noted as well.
Rusina, R; Bourdain, F; Matej, R
Multiple system atrophy (MSA) is a neurodegenerative disorder typically characterised by cerebellar dysfunction, parkinsonism, pyramidal signs and dysautonomy. Cognitive impairement is usually limited to a moderate subcortical dysexecutive syndrom. We report the case of a 62-year-old woman suffering from MSA who progressively developed severe dementia. Neuropathological examination confirmed the diagnosis of definite MSA and also showed histopathological hallmarks of Alzheimer's disease. This association is extremely rare in the literature. Our observation confirmes that franc dementia in MSA should prompt a search for another associated cause and underlines the usefulness of neuropathological verifications in atypical clinical pictures.
Pauer, Frédéric; Schmidt, Katharina; Babac, Ana; Damm, Kathrin; Frank, Martin; von der Schulenburg, J-Matthias Graf
The Analytic Hierarchy Process (AHP) is increasingly used to measure patient priorities. Studies have shown that there are several different approaches to data acquisition and data aggregation. The aim of this study was to measure the information needs of patients having a rare disease and to analyze the effects of these different AHP approaches. The ranking of information needs is then used to display information categories on a web-based information portal about rare diseases according to the patient's priorities. The information needs of patients suffering from rare diseases were identified by an Internet research study and a preliminary qualitative study. Hence, we designed a three-level hierarchy containing 13 criteria. For data acquisition, the differences in outcomes were investigated using individual versus group judgements separately. Furthermore, we analyzed the different effects when using the median and arithmetic and geometric means for data aggregation. A consistency ratio ≤0.2 was determined to represent an acceptable consistency level. Forty individual and three group judgements were collected from patients suffering from a rare disease and their close relatives. The consistency ratio of 31 individual and three group judgements was acceptable and thus these judgements were included in the study. To a large extent, the local ranks for individual and group judgements were similar. Interestingly, group judgements were in a significantly smaller range than individual judgements. According to our data, the ranks of the criteria differed slightly according to the data aggregation method used. It is important to explain and justify the choice of an appropriate method for data acquisition because response behaviors differ according to the method. We conclude that researchers should select a suitable method based on the thematic perspective or investigated topics in the study. Because the arithmetic mean is very vulnerable to outliers, the geometric mean
Svenstrup, Dan Tito; Jørgensen, Henrik L; Winther, Ole
on the use of web search, social media and data mining in data repositories for medical diagnosis. We compare the retrieval accuracy on 56 rare disease cases with known diagnosis for the web search tools google.com, pubmed.gov, omim.org and our own search tool findzebra.com. We give a detailed description...... in technology and access to high quality data have opened new possibilities for aiding the diagnostic process. Specialized search engines, data mining tools and social media are some of the areas that hold promise....
Hytönen, Marjo K; Arumilli, Meharji; Lappalainen, Anu K; Owczarek-Lipska, Marta; Jagannathan, Vidhya; Hundi, Sruthi; Salmela, Elina; Venta, Patrick; Sarkiala, Eva; Jokinen, Tarja; Gorgas, Daniela; Kere, Juha; Nieminen, Pekka; Drögemüller, Cord; Lohi, Hannes
One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions.
M. OSWALDO BUSTAMANTE RÚA
Full Text Available Se presentan los resultados de un estudio experimental en reología de suspensiones, donde se encuentra como principal conclusión que la magnitud del Esfuerzo de Cedencia τo, depende fuertemente de la velocidad de aplicación del esfuerzo de cizalladura, ligado con la memoria de la suspensión analizada a través del tiempo de relajación tR. Además de la velocidad de aplicación del esfuerzo de cizalladura, el Esfuerzo de Cedencia τo para todas las suspensiones minerales depende del empaquetamiento del sistema particulado que forma parte de la suspensión, expresado a través de la fracción volumétrica de sólidos φ y de la granulometría del sistema particulado que forma parte de la suspensión. Se pudo concluir que la magnitud del Esfuerzo de Cedencia τo no es una propiedad invariante de la suspensión, ya que existen muchos valores para ella dependiendo de la dinámica de la deformación, e inclusive; existe un caso particular en toda deformación en la cual el Esfuerzo de Cedencia puede ser cero.
V. G. Barskova
Full Text Available 33-year-old patient with Behcet's disease developed severe lesion of gastro-intestmal tract involving esophagus. Behcet’s disease diagnosis was verified by recurrent aphtous stomatitis, genital ulcers and erythema nodosum. Peculiarity of this case was wide involving of gastro-iniestinal tract with multiple ulcers in ileocecum and esophagitis leading to the development of diverticulum and gullet narrowing. This case demonstrates the results of late diagnosis of the disease as the diagnosis was determined in IS years after the onset of first symptoms.
Specht, L.; Nissen, N.I.
analysis, infradiaphragmatic presentation turned out to be an adverse prognostic factor with regard to disease-free survival, whereas it was not of significant independent prognostic value with regard to overall survival. Staging laparotomy in 11/35 infradiaphragmatic patients revealed 1 stage-IV case......Out of 323 patients with Hodgkin's disease CS I or II treated during the period 1969 to 1983 at Denmark's Finsen Institute, 35 presented with infradiaphragmatic disease. Patients with infradiaphragmatic presentation were older than patients with supradiaphragmatic presentation and were more often...... in stage II as opposed to stage I. NS histology was less prevalent among infradiaphragmatic than among supradiaphragmatic patients. Disease-free survival and overall survival was poorer in infradiaphragmatic patients. When other factors of prognostic importance were taken into account in a multivariate...
... of Award Clinical Terms of Award Restriction for China Clinical Terms Guidance Compliance Sample Letter Inclusion Codes ... Division of AIDS Division of Allergy, Immunology, and Transplantation Division of Microbiology and Infectious Diseases Division of ...
Garg, Paritosh; Gupta, Nikhil; Arora, Mohit
Introduction: Tuberculosis is a major health problem worldwide, more so in Asian countries and especially India. Being a communicable disease, it can affect the lives of many people. Tuberculosis has varied manifestations and can affect almost every part of the human body. Pulmonary tuberculosis is the most common form. Poncet disease (tuberculous rheumatism) is a polyarticular arthritis that occurs during acute tuberculosis infection in which no mycobacterial involvement can be found or no other known cause of polyarthritis is detected. Case presentation: We describe an atypical presentation of active pulmonary tuberculosis with monoarticular Poncet disease of the right knee in a 24-year-old woman. Discussion: The diagnosis of Poncet disease is mainly clinical with exclusion of other causes. It generally presents as an acute or subacute form; however, chronic forms have been described in the literature. PMID:27455057
Wu, Te Chang [Chi-Mei Foundation Hospital, Tainan (China); Guo, Wan Yuo; Wu, Hsiu Mei; Chang, Feng Chi; Shiau, Cheng Ying; Chung, Wen Yuh [Taipei Veterans General Hospital, Taipei (China)
A 36-year-old man was diagnosed with a right temporal lobe grade II cerebral arteriovenous malformation (cAVM) and was treated with radiosurgery. At nine months after the cAVM radiosurgery, the patient began to develop bilateral focal narrowing at the M1 segments of the bilateral middle cerebral arteries. The narrowing progressively deteriorated as was demonstrated on longitudinal serial follow- up MR imaging. X-ray angiography performed at 51 months after radiosurgery confirmed that the cAVM was cured and a diagnosis of moyamoya disease. To the best of our knowledge, this is the first case of cAVM-associated moyamoya disease that developed after radiosurgery. Given the chronological sequence of disease development and radiation dose distribution of radiosurgery, it is proposed that humoral or unknown predisposing factors, rather than direct radiation effects, are the cause of moyamoya disease associated with cAVM.
Schaefer, Corinna; Brunsmann, Frank; Siegert, Svenja
Information for patients with rare diseases has to adhere to strict quality criteria in order to support individual treatment decisions or coping strategies. However, developers are facing specific challenges: For example, the evidence is often insufficient or of very low quality. In the context of the National Action League for People with Rare Diseases (NAMSE), criteria have been developed that assure high-quality information on rare diseases. Core criteria comprise the involvement of patients or their advocates in all stages of the development process, the systematic search and assessment of the evidence, systematic collection of patient experience, transparency in terms of people involved and funding, and nondirective and neutral formulation of content and documentation of the process. In a joint project between the Alliance for Chronic Rare Diseases (ACHSE e. V.) and the German Agency for Quality in Medicine (ÄZQ), ten short information leaflets on different rare diseases have been developed in the past three years, conceived to show the applicability of these criteria. First experiences with this format show that the criteria are adaptive to a broad range of diverse rare diseases and settings. Involving patients and their advocates throughout the whole development process - from prioritization to development of methods and provision of patient experience and coping strategies - is crucial. Insufficient evidence remains a challenge. The examples show that in the absence of proven findings, information that matters to patients and reflects this uncertainty is feasible.
Abbas Ali Rafighdoust
Full Text Available Absence of pericardium is a rare type of pericardial disorders. Left sided pericardial absence is more common than the right one. This disorder may present with a variety of signs and symptoms or abnormalities in electrocardiography and echocardiography. In this report, we discussed diagnosis of partial absence of pericardium in a 52-year-old man presented with a dull left-sided chest pain from 4 months ago with special electrocardiographic features. The axis deviations in his serial electrocardiograms led us to further evaluations with possible diagnosis of pericardial absence. His echocardiography and Magnetic Resonance Imaging (MRI confirmed the suspicion of pericardial absence. Suspicion of potentially life-threatening cardiac abnormalities should remain even while facing atypical chest pain or other non-specific symptoms. In this case, abnormal electrocardiographic and chest X-Ray findings together with echocardiography were all helpful in referring the patient for cardiac MRI as the imaging modality of choice in such cases.
Full Text Available Hepatic angiomyolipoma is an extremely rare benign hamartomatous lesion. Situs inversus totalis is a genetic condition occurring in 0.01% of the population. Following the kidney, the liver is the second most common site of angiomyolipoma. No consensus on the treatment of hepatic angiomyolipoma has been reached. However, the majority of these tumours are managed conservatively. Situs inversus totalis presents difficulties for procedures and is most commonly an incidental finding. These two conditions have not previously been reported and no genetic link has been established between them. This paper reports the association of both conditions in a 74-year-old female, reviews the literature, and presents CT imaging of the case.
Full Text Available We report a case of isolated ossification of iliopsoas with ankylosis of the left hip in a 27-year-old female. The patient was diagnosed to have Moyamoya disease, a rare chronic occlusive disorder of cerebrovascular circulation following an acute onset of hemiplegia. The patient presented 9 months later to us with ankylosis of left hip which was successfully treated by surgical excision of the heterotopic bone and there was no recurrence at the end of 5 years. A review of literature failed to reveal a similar case with isolated and complete ossification of iliopsoas muscle associated with Moyamoya disease which required surgical intervention. Surgical excision resulted in dramatic improvement in the quality of life. Surgical excision of neurogenic type of heterotopic ossification is a very successful procedure and timely intervention after maturity of mass is very important to prevent the onset of secondary complications and to avoid recurrence.
Ruiz, Elena; Ramalle-Gómara, Enrique; Quiñones, Carmen
Our objective was to analyse the coverage of hospital discharge data and the mortality registry (MR) of La Rioja to ascertain motor neuron disease (MND) cases to be included in the Spanish National Rare Diseases Registry. MND cases that occurred in La Rioja during the period 1996-2011 were selected from hospital discharge data and the MR by means of the International Classification of Diseases. Review of the medical histories was carried out to confirm the causes of death reported. Characteristics of the population with MND were analysed. A total of 133 patients with MND were detected in La Rioja during the period 1996-2011; 30.1% were only recorded in the hospital discharges data, 12.0% only in the MR, and 57.9% were recorded by both databases. Medical records revealed a miscoding of patients who had been diagnosed with progressive supranuclear palsy but were recorded in the MR with an MND code. In conclusion, the hospital discharges data and the MR appear to be complementary and are valuable databases for the Spanish National Rare Diseases Registry when MNDs are properly codified. Nevertheless, it would be advisable to corroborate the validity of the MR as data source since the miscoding of progressive supranuclear palsy has been corrected.
Perros, P; Hegedüs, L; Bartalena, L; Marcocci, C; Kahaly, G J; Baldeschi, L; Salvi, M; Lazarus, J H; Eckstein, A; Pitz, S; Boboridis, K; Anagnostis, P; Ayvaz, G; Boschi, A; Brix, T H; Currò, N; Konuk, O; Marinò, M; Mitchell, A L; Stankovic, B; Törüner, F B; von Arx, G; Zarković, M; Wiersinga, W M
Graves' orbitopathy (GO) is an autoimmune condition, which is associated with poor clinical outcomes including impaired quality of life and socio-economic status. Current evidence suggests that the incidence of GO in Europe may be declining, however data on the prevalence of this disease are sparse. Several clinical variants of GO exist, including euthyroid GO, recently listed as a rare disease in Europe (ORPHA466682). The objective was to estimate the prevalence of GO and its clinical variants in Europe, based on available literature, and to consider whether they may potentially qualify as rare. Recent published data on the incidence of GO and Graves' hyperthyroidism in Europe were used to estimate the prevalence of GO. The position statement was developed by a series of reviews of drafts and electronic discussions by members of the European Group on Graves' Orbitopathy. The prevalence of GO in Europe is about 10/10,000 persons. The prevalence of other clinical variants is also low: hypothyroid GO 0.02-1.10/10,000; GO associated with dermopathy 0.15/10,000; GO associated with acropachy 0.03/10,000; asymmetrical GO 1.00-5.00/10,000; unilateral GO 0.50-1.50/10,000. GO has a prevalence that is clearly above the threshold for rarity in Europe. However, each of its clinical variants have a low prevalence and could potentially qualify for being considered as a rare condition, providing that future research establishes that they have a distinct pathophysiology. EUGOGO considers this area of academic activity a priority.
Svenstrup, Dan; Jørgensen, Henrik L; Winther, Ole
Physicians and the general public are increasingly using web-based tools to find answers to medical questions. The field of rare diseases is especially challenging and important as shown by the long delay and many mistakes associated with diagnoses. In this paper we review recent initiatives on the use of web search, social media and data mining in data repositories for medical diagnosis. We compare the retrieval accuracy on 56 rare disease cases with known diagnosis for the web search tools google.com, pubmed.gov, omim.org and our own search tool findzebra.com. We give a detailed description of IBM's Watson system and make a rough comparison between findzebra.com and Watson on subsets of the Doctor's dilemma dataset. The recall@10 and recall@20 (fraction of cases where the correct result appears in top 10 and top 20) for the 56 cases are found to be be 29%, 16%, 27% and 59% and 32%, 18%, 34% and 64%, respectively. Thus, FindZebra has a significantly (p data have opened new possibilities for aiding the diagnostic process. Specialized search engines, data mining tools and social media are some of the areas that hold promise.
Full Text Available Las enfermedades raras plantean una serie de retos a los afectados y sus familias: el diagnóstico, afrontar los síntomas, la información sobre la enfermedad, obtención de atención sanitaria adecuada, disponibilidad de fármacos, discapacidad e impacto emocional. Los niños con enfermedades raras constituyen un grupo poblacional muy importante desde el punto de vista de los servicios sanitarios y sociales, y las familias deben proporcionar cuidados durante largo tiempo a estos niños enfermos. La repercusión de las enfermedades raras en los niños es de gran alcance, extendiéndose más allá de ellos mismos, a todas las personas de su entorno. Son múltiples las facetas de la vida afectadas, incluyendo las relaciones familiares y sociales, el bienestar económico o las actividades cotidianas. La evaluación de las necesidades en las enfermedades raras es una fase crítica para proporcionar una atención sanitaria de alta calidad y conseguir la satisfacción del enfermo y su familia. Los hallazgos de diferentes estudios han puesto de manifiesto que las personas con enfermedades raras tienen necesidades médicas y sociales. Las necesidades sociales están adquiriendo una gran relevancia en los países desarrollados, en los que los servicios sanitarios, aún con limitaciones, tienen mayor disponibilidad que los servicios sociales. Por consiguiente, parece necesario que los servicios sanitarios y sociales para las personas con enfermedades raras deben mejorarse para abordar las necesidades de los pacientes y proporcionar mejor apoyo a las familias. En este sentido, sigue siendo necesario disponer de instrumentos validados con buenas propiedades psicométricas para valorar la calidad de la asistencia en función de las necesidades de los pacientes y sus familias.All rare diseases present a common set of challenges to the sufferers and their families: diagnosis, dealing with symptoms, health information, obtaining helpful medical care
Daniel González Lomelí; María de los Ángeles Maytorena Noriega
El objetivo del presente estudio fue determinar si existen relaciones entre las variables latentes, factores de carrera, seguridad vocacional y el esfuerzo académico en una muestra constituida por 229 estudiantes de primer semestre de las Licenciaturas en Psicología y Químico-Biólogos de una universidad pública. Se utilizó el Inventario Ampliado de Factores de Carrera (IAFC). Se realizaron análisis estadísticos descriptivos de las variables demográficas y análisis factoriales de e...
A. Bautista Hernández; J.H. Camacho García; M. Salazar Villanueva; E. Chigo Anota; A. Macias Cervantes
A temperatura y presión ambiente el Ti, Zr y Hf cristalizan en la fase hexagonal compacta. Recientemente se ha reportado que estos elementos son élasticamente metaestables  en la estructura cúbica centrada en las caras (fcc). En este trabajo presentamos el esfuerzo triaxial ideal de los metales Ti, Zr y Hf con estructura fcc, obtenido mediante cálculos de primeros principios usando la teoría del funcional de la densidad. Se usó la aproximación de gradiente generalizado y local de la densi...
Conclusion: To the best of our knowledge, this patient is the oldest of reported patients diagnosed with XH. Steroid therapy may be effective to XH temporarily. XH should be considered when diagnosing pituitary cystic lesions in elderly patients with autoimmune disease.
Full Text Available Castleman's disease is a distinct form of lymph node hyperplasia divided into a solitary and a multicentric type. The solitary type occurs most commonly in the mediastinum and is usually asymptomatic. We present a patient with Castleman's disease of the hyaline-vascular solitary type located in the retroperitoneum. The patient was a 38-year-old male, who presented to our hospital with fever. The imaging workup revealed a retroperitoneal mass, measuring 4 × 6 cm, located lateral to the aorta, inferior to the left renal artery and vein, and posterior to the left testicular vein. At workup, a solid hepatic lesion, 3 cm in diameter, located in the left lobe of the liver, segment IV, was also identified. Both lesions were surgically excised. The retroperitoneal tumor had the features of angiofollicular hyperplasia (Castleman's disease, hyaline-vascular type, whereas a diagnosis of focal nodular hyperplasia was made for the hepatic lesion. The patient is well at fourty months followup postoperatively. Surgical excision is the treatment of choice for unifocal Castleman's disease.
Brix, Thomas H; Hegedüs, Laszlo; Weetman, Anthony P;
prevalence than the controls: NISAb: 17% vs 0% (P Hashimoto's thyroiditis (HT) had NISAb, (P ...OBJECTIVE: Antibodies against thyroglobulin, thyroid peroxidase and the TSH receptor are accepted as pathophysiological and diagnostic biomarkers in autoimmune thyroid disease (AITD). In contrast, the prevalence, aetiology and clinical relevance of autoantibodies against the human sodium...
Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C l...
Pontocerebellar hypoplasia (PCH) is a recessive neurodegenerative disease with, in most cases, a prenatal onset. The patients suffer from severe intellectual and motor impairments. The majority of patients dies in childhood. This thesis describes novel genes and genotype-phenotype correlations in PC
Emison, Eileen Sproat; Garcia-Barcelo, Merce; Grice, Elizabeth A.; Lantieri, Francesca; Amiel, Jeanne; Burzynski, Grzegorz; Fernandez, Raquel M.; Hao, Li; Kashuk, Carl; West, Kristen; Miao, Xiaoping; Tam, Paul K. H.; Griseri, Paola; Ceccherini, Isabella; Pelet, Anna; Jannot, Anne-Sophie; de Pontual, Loic; Henrion-Caude, Alexandra; Lyonnet, Stanislas; Verheij, Joke B. G. M.; Hofstra, Robert M. W.; Antinolo, Guillermo; Borrego, Salud; McCallion, Andrew S.; Chakravarti, Aravinda
The major gene for Hirschsprung disease (HSCR) encodes the receptor tyrosine kinase RET. In a study of 690 European- and 192 Chinese-descent probands and their parents or controls, we demonstrate the ubiquity of a >4-fold susceptibility from a C -> T allele (rs2435357: p = 3.9 x 10(-43) in European
Bax, Nathalie M.; Fakin, Ana; Groenewoud, Joannes M. M.; Klevering, B. Jeroen; Moore, Anthony T.; Michaelides, Michel; Webster, Andrew R.; van der Wilt, Gert Jan; Hoyng, Carel B.
Background Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options—including gene therapy—are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date) and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including variable rates of functional and structural progression, thereby potentially limiting the ability of phase I/II clinical trials to assess efficacy of novel therapies with few patients. To accommodate this problem, we developed and validated a sensitive and reliable composite clinical trial endpoint for disease progression based on structural measurements of retinal degeneration. Methods and findings We used longitudinal data from early-onset Stargardt patients from the Netherlands (development cohort, n = 14) and the United Kingdom (external validation cohort, n = 18). The composite endpoint was derived from best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography. Weighting optimization techniques excluded visual acuity from the composite endpoint. After optimization, the endpoint outperformed each univariable outcome, and showed an average progression of 0.41° retinal eccentricity per year (95% confidence interval, 0.30–0.52). Comparing with actual longitudinal values, the model accurately predicted progression (R2, 0.904). These properties were largely preserved in the validation cohort (0.43°/year [0.33–0.53]; prediction: R2, 0.872). We subsequently ran a two-year trial simulation with the composite endpoint, which detected a 25% decrease in disease progression with 80% statistical power using only 14 patients. Conclusions These results suggest that a multimodal endpoint, reflecting structural macular changes, provides a
Karla Lais Pegas
Full Text Available Lipoprotein glomerulopathy (LPG is a rare autosomal recessive glomerulopathy associated with the deposition of lipoprotein thrombi in the capillary lumina due to apoE gene mutations. Abnormal plasma lipoprotein profile and marked increase in serum apoliprotein E (apoE are characteristic clinical data. The compromised patients can present nephrotic syndrome, hematuria, and progressive renal failure. Herein, the authors present the first described case of LPG in a Brazilian male patient, 11 years, who presented with a steroid-resistant nephrotic syndrome. Renal function was normal. Kidney biopsy showed markedly enlarged glomerulus, with dilated capillary loops and weak eosinophilic lipoprotein thrombi in the capillary lumina. Interstitium, tubules, arteries, and veins showed normal histologic aspect. Genotypic study for the apoE gene showed the presence of the alleles E3 and E4. The diagnosis of LPG was then performed. The patient received lipid-lowering treatment. After 2 years of follow-up, renal function is gradually decreasing, with persisting heavy proteinuria, despite a marked decrease in serum cholesterol and triglycerides levels.
Full Text Available Pleural involvement is an uncommon but well recognized complication of chronic pancreatitis, mainly in the form of pleural effusion affecting the left hemithorax. Pancreatic pseudocyst extending to the posterior mediastinum with or without communication with the pleural space is another rare form of this involvement.The treatment of chronic pancreatic pleural effusions and pancreatic pseudocysts generally starts with a conservative approach including bowel rest, drainage of the pleural effusion by repeated thoracentesis or a chest tube, and total parenteral nutrition (TPN for a period of time determined by the clinical course. Other treatment modalities including percutaneous drainage, endoscopic retrograde cholangiopancreatogram (ERCP with stenting of the pancreatic duct and surgical drainage are used if conservative approaches fail.We report a patient with a complicated pancreatic pseudocyst who showed an involvement of the posterior mediastinum and right pleural space, with conspectus sparing of the left hemithorax. The patient had a prolonged and complicated course that included recurrence of the pseudocyst with oral feedings and the development of a splenic artery aneurysm. Some of the above findings have been reported separately as uncommon complications of chronic pancreatitis and pancreatic pseudcyst, but to our knowledge a single case with all these complications was not published in the English literature.
Full Text Available Non-traumatic elbow pain is rarely seen in children and pre-adolescents. Osteochondral lesions may be the source of chronic elbow pain, swelling, and loss of motion in children or adolescents. Osteochondritis dissecans (OCD is described as a lesion of subchondral bone resulting in separation of the articular cartilage and subchondral bone. It is found primarily in the knee, ankle, and elbow joints. Since osteochondrosis of the elbow primarily involves capitellum, few papers involving osteonecrosis of the trochlea have been reported. This paper discusses a pre-adolescent boy with clinical and radiographic signs consistent with unilateral osteochondral lesion of the trochlea humeri, with no history of recent trauma. The patient had insidious onset of right elbow pain during daily activities for the last 3 weeks. After usage of long arm splint for 2 weeks, persistence of the symptoms necessitated MRI of the affected elbow. After the diagnosis, non-operative management was achieved. Care should be taken for the affected children to recognize any residual deformity and to treat it properly at follow up.
Full Text Available It is a rare genetic disorder characterized by the absence of the radius bone in the forearm and a dramatically reduced platelet count. This syndrome may occur as a part of the 1q21.1 deletion syndrome. Symptoms of thrombocytopenia or a lowered platelet count leads to bruising and potentially life-threatening haemorrhage. Affected children who survive this period and do not have damaging haemorrhages in the brain usually have a normal life expectancy and normal intellectual development. Other common links between with TAR seem to include heart problems, kidney problems, knee joint problems, frequently lactose intolerance and often thumb hypoplasia. The incidence is 0.5-1 per 100,000 live births. Mutations in the RBM8A gene cause TAR syndrome. It is inherited in an autosomal recessive pattern. This disorder is to be differentiated from Holt-Oram syndrome, which has similar presentation. Prevention of bleeding with physiotherapy and occupational therapy are mainstay of management. With this case report we try to discuss the complexity of the condition and its management in the neonatal period.
Scagni, Paola; Peisino, Maria Grazia; Bianchi, Maurizio; Morello, Maura; Sardi, Nicola; Linari, Alessandra; Mastrodicasa, Luana; Madon, Enrico; Pecco, Paola
Kikuchi-Fujimoto disease, a benign and unusual self-limiting histiocytic necrotizing lymphadenitis of unknown origin, should be included in the differential diagnosis of lymphadenopathy and fever of unknown origin. This disease mostly affects young Asian women and has rarely been reported in children, thus remaining a poorly recognized entity that is frequently confused with malignant lymphoma. The authors describe two children with Kikuchi-Fujimoto disease, with particular attention to diagnostic approach and clinical and histologic features of the disease.
Ana Maria Teixeira Verçoza
Full Text Available Cat Scratch Disease (CSD is an infectious disorder which appears after cat scratching particularly in children and adolescents. Bartonella henselae is the etiologic agent more frequently involved. There are only a few recent reports demonstrating the disease after transplantation, although the illness is not infrequent in immunologically competent people. Indeed CSD in transplant receptors has only been recently emphasized in the literature and it was concluded that fever and lymphadenopathy in patients who had been exposed to cats should prompt clinicians to maintain a suspicion for the infection. In this report CSD infecting a renal transplanted adolescent complaining of headache, blurred vision and fever, presenting a cat scratching lesion in the right arm, with a bilateral painful cervical lymphadenopathy was related. He also presented indirect immunofluorescency identifying that the two subtype's titles of Bartonella-henselae and quintana- were elevated. Treatment with doxicicline e rifampicin was introduced and the patient became asymptomatic in about 3 weeks.
Full Text Available A 48-year-old woman with a past medical history of seizures and end-stage renal disease secondary to obstructive uropathy from retroperitoneal fibrosis presented to the emergency department with seizures and altered mental status. A Glasgow Coma Scale of 4 prompted intubation, and she was subsequently admitted to the intensive care unit. Magnetic resonance imaging of the brain performed to elucidate the aetiology of her seizure showed a dural-based mass within the left temporoparietal lobe as well as mass lesions within the orbits. Further imaging showed extensive retroperitoneal fibrosis extending to the mediastinum with involvement of aorta and posterior pleural space. Imaging of the long bones showed bilateral sclerosis and cortical thickening of the diaphyses. Imaging of the maxillofacial structures showed osseous destructive lesions involving the mandible. These clinical and radiological features were consistent with a diagnosis of Erdheim-Chester disease; however, the patient’s skin biopsy was consistent with Langerhans cell histiocytosis.
Nabi, Shahzaib; Arshad, Adeel; Jain, Tarun; Virk, Fawad; Gulati, Rohit; Awdish, Rana
A 48-year-old woman with a past medical history of seizures and end-stage renal disease secondary to obstructive uropathy from retroperitoneal fibrosis presented to the emergency department with seizures and altered mental status. A Glasgow Coma Scale of 4 prompted intubation, and she was subsequently admitted to the intensive care unit. Magnetic resonance imaging of the brain performed to elucidate the aetiology of her seizure showed a dural-based mass within the left temporoparietal lobe as well as mass lesions within the orbits. Further imaging showed extensive retroperitoneal fibrosis extending to the mediastinum with involvement of aorta and posterior pleural space. Imaging of the long bones showed bilateral sclerosis and cortical thickening of the diaphyses. Imaging of the maxillofacial structures showed osseous destructive lesions involving the mandible. These clinical and radiological features were consistent with a diagnosis of Erdheim-Chester disease; however, the patient's skin biopsy was consistent with Langerhans cell histiocytosis. PMID:26579323
Background: Pain is regarded as one of the most common nonmotor symptoms in Parkinson's disease (PD). In particular, musculoskeletal pain has been reported as the most common type of PD-associated pain. Crowned dens syndrome (CDS), related to microcrystalline deposition in the periodontoid process, is the main cause of acute or chronic cervical pain. Case Presentation: This report describes the case of an 87-year-old woman who had severe bradykinesia, muscle rigidity, gait disturbance and nec...
Verma, Rajesh; Bhandari, Aveg; Tiwari, Navin; Chaudhari, Tejendra S
Wilson disease (WD) is one of the few inherited but treatable disorder mainly affecting the liver and brain resulting in severe disability or death if left untreated. Hence, it is important to keep a high index of suspicion for diagnosing this clinical entity in appropriate clinical settings. The clinical presentation can be quite variable and they may present solely with neurological features sans hepatic symptoms. Such neurological manifestations usually follow subacute to chronic course. A...
Arooj, Shumaila; Mubarak, Fatima; Azeemuddin, Muhammad; Sajjad, Zafar; Jilani, Wasey
Hirayama Disease is a disease of young adults lying in the age group between twenty to thirty years. It is an extremely uncommon disorder. Its other synonyms are juvenile muscular atrophy of the distal upper extremity (JMADUE) or monomelic amyotrophy (MMA). A previously healthy 25-year-old man presented with gradually increasing weakness in both hands for the past few years. There was neither history of trauma nor family history of neuromuscular disease. MRI was advised. Routine cervical sagittal MR images (Non-flexion or extension) revealed cord flattening and atrophy at C5 to C7 levels.There was evidence of syrinx. Flexion MRI was performed later on. Midline sagittal T1- and T2-weighted images of the cervical spine showed anterior displacement of the cervical cord with marked flattening of cord. The patient was advised to modify his posture, avoid flexion and to apply cervical collar. Physiotherapy was started to improve the tone of muscles. In case of deterioration of symptoms he was advised to consult for surgery. The purpose of this case report is to show the importance of dynamic scan in symptomatic patients especially in their second or third decade with progressive upper limb weakness. Mostly the scanning in neutral posture does not reveal any significant cord compression. Similarly a normal looking thecal sac with preserved anterior and posterior thecal sleeves without disc disease dramatically changes on change of posture. This case shows the importance of dynamic scanning in symptomatic patients with progressive upper limb weakness and with no obvious cause of the cord changes on routine MR images. Cervical collar, physiotherapy and in resistant cases surgery is recommended for management.
Migita, Kiyoshi; Izumi, Yasumori; Jiuchi, Yuka; Iwanaga, Nozomi; Kawahara, Chieko; Agematsu, Kazunaga; Yachie, Akihiro; Masumoto, Junya; Fujikawa, Keita; Yamasaki, Satoshi; Nakamura, Tadashi; Ubara, Yoshifumi; Koga, Tomohiro; Nakashima, Yoshikazu; Shimizu, Toshimasa
Background The aim of this study was to evaluate the clinical manifestations and prevalence of familial Mediterranean fever (FMF) in Japanese patients with unexplained fever and rheumatic manifestations. Methods We enrolled 601 patients with unexplained fever or suspected FMF throughout Japan between 2009 and 2015. Patients were divided into three groups according to Tel Hashomer criteria: sure FMF, probable FMF, and non-FMF patients, including definitive rheumatic diseases. Mutation detectio...
Full Text Available Parkinson`s disease (PD is the most common neurodegenerative disease and is characterized by tremor, rigidity and akinesia. Diagnosis is clinical in the majority of the patients. Patients with PD may have stooped posture but some of them develop different types of postural and striatal deformities. Usually these deformities are more common in atypical parkinsonian disorders such as progressive supranuclear palsy and multisystem atrophy. But in many studies it has been highlighted that these may also be present in approximately one third of PD patients leading to severe disability. These include antecollis or dropped head, camptocormia, p0 isa syndrome, scoliosis, striatal hands and striatal toes. The pathogenesis of these deformities is a complex combination of central and peripheral influences such as rigidity, dystonia and degenerative skeletal changes. Duration of parkinsonism symptoms is an important risk factor and in majority of the patients these deformities are seen in advanced statge of the disease. The patients with such symptoms may initially respond to dopaminergic medications but if not intervened they may become fixed and difficult to treat. Pain and restriction of movement are most common clinical manifestations and these may mimick symptoms of musculoskeletal disorders like rheumatoid arthritis. Early diagnosis is important as the patients may respond to adjustment in dopaminergic medications. Recent advances such as deep brain stimulation (DBS and ultrasound guided botulinum toxin injection are helpful in management of these deformities in patients with PD.
Pandey, Sanjay; Garg, Hitesh
Parkinson`s disease (PD) is the most common neurodegenerative disease and is characterized by tremor, rigidity and akinesia. Diagnosis is clinical in the majority of the patients. Patients with PD may have stooped posture but some of them develop different types of postural and striatal deformities. Usually these deformities are more common in atypical parkinsonian disorders such as progressive supranuclear palsy and multisystem atrophy. But in many studies it has been highlighted that these may also be present in approximately one third of PD patients leading to severe disability. These include antecollis or dropped head, camptocormia, p0 isa syndrome, scoliosis, striatal hands and striatal toes. The pathogenesis of these deformities is a complex combination of central and peripheral influences such as rigidity, dystonia and degenerative skeletal changes. Duration of parkinsonism symptoms is an important risk factor and in majority of the patients these deformities are seen in advanced statge of the disease. The patients with such symptoms may initially respond to dopaminergic medications but if not intervened they may become fixed and difficult to treat. Pain and restriction of movement are most common clinical manifestations and these may mimick symptoms of musculoskeletal disorders like rheumatoid arthritis. Early diagnosis is important as the patients may respond to adjustment in dopaminergic medications. Recent advances such as deep brain stimulation (DBS) and ultrasound guided botulinum toxin injection are helpful in management of these deformities in patients with PD.
Full Text Available TREX1 (DNase III is an exonuclease involved in response to oxidative stress and apoptosis. Heterozygous mutations in TREX1 were previously observed in patients with systemic lupus erythematosus (SLE and Sjögren's syndrome (SS. We performed a mutational analysis of the TREX1 gene on three autoimmune diseases: SLE (210 patients and SS (58 patients, to confirm a TREX1 involvement in the Italian population, and systemic sclerosis (SSc, 150 patients because it shares similarities with SLE (presence of antinuclear antibodies and connective tissue damage. We observed 7 variations; two of these are novel nonsynonymous variants (p.Glu198Lys and p.Met232Val. They were detected in one SS and in one SSc patient, respectively, and in none of the 200 healthy controls typed in this study and of the 1712 published controls. In silico analysis predicts a possibly damaging role on protein function for both variants. The other 5 variations are synonymous and only one of them is novel (p.Pro48Pro. This study contributes to the demonstration that TREX1 is involved in autoimmune diseases and proposes that the spectrum of involved autoimmune diseases can be broader and includes SSc. We do not confirm a role of TREX1 variants in SLE.
Rusina, Robert; Pazdera, Ladislav; Kulišťák, Petr; Vyšata, Oldřich; Matěj, Radoslav
We describe a patient with corticobasal syndrome in whom neuropathological examination on autopsy revealed Pick and Alzheimer diseases in comorbidity. Corticobasal degeneration is a tauopathy usually associated with asymmetric parkinsonism, parietal lobe involvement, and cognitive impairment. Corticobasal syndrome is the clinical presentation of corticobasal degeneration without neuropathological confirmation. A 66-year-old right-handed man slowly developed speech difficulties, right-hand clumsiness, and forgetfulness. His speech apraxia progressed to mutism with preserved comprehension, and his clumsiness progressed to severe apraxia involving both hands. He developed behavioral changes and severe amnesia. All of these features were consistent with corticobasal syndrome. His loss of episodic, verbal, and visuospatial memory suggested Alzheimer disease; however, beyond his frontotemporal neuropsychological profile, he had few symptoms characteristic of frontal lobe dementia. Magnetic resonance imaging scans showed worsening temporal, frontal, and parietal atrophy, predominant in the left hemisphere. Neuropathological examination at autopsy revealed abundant neuritic plaques and neurofibrillary tangles consistent with fully developed Alzheimer disease, as well as numerous intraneuronal Pick bodies in the frontotemporal lobes. Our findings confirm the importance of clinical and neuropathological correlations in patients with atypical neurodegenerative dementias.
Full Text Available Eleftherios Koudounarakis, Nikolaos Chatzakis, Ioannis Papadakis, Irene Panagiotaki, George VelegrakisDepartment of Otorhinolaryngology, University Hospital of Heraklion, Crete, GreeceAbstract: Nasal bleeding is a frequent problem for patients receiving anticoagulant agents. Most cases are successfully managed with anterior or posterior nasal packing. However, the complications of nasal packing should be always considered. We report the case of a 78-year-old man with Alzheimer’s disease who was treated for anterior epistaxis with anterior nasal packing using three pieces of antibiotic-soaked gauze. Two days later, the patient was admitted to the emergency department in respiratory distress. A chest x-ray demonstrated atelectasis of the right lung. During an examination of the nasal cavities, the nasal packing was removed, and one of the gauze pieces was missing. The patient underwent rigid bronchoscopy, and the missing gauze was found to be obstructing the right main bronchus. The patient’s respiratory function improved considerably after removal of the foreign body. It is assumed that gauze packs should be used with caution in patients with an impaired level of consciousness and neurodegenerative diseases.Keywords: epistaxis, nasal packing, aspiration, Alzheimer’s disease, cough reflex
Stephen Fraedrich; T Harrington; C Bates; J Johnson; L. Reid; Glenda Susan Best; T Leininger; Tracy Hawkins
Laurel wilt, caused by Raffaelea lauricola, has been responsible for extensive losses of redbay (Persea borbonia) in South Carolina and Georgia since 2003. Symptoms of the disease have been noted in other species of the Lauraceae such as the federally endangered pondberry (Lindera melissifolia) and the threatened pondspice (Litsea aestivalis). Pondberry and pondspice...
Nadia K. Litterman
Full Text Available Rare disease research has reached a tipping point, with the confluence of scientific and technologic developments that if appropriately harnessed, could lead to key breakthroughs and treatments for this set of devastating disorders. Industry-wide trends have revealed that the traditional drug discovery research and development (R&D model is no longer viable, and drug companies are evolving their approach. Rather than only pursue blockbuster therapeutics for heterogeneous, common diseases, drug companies have increasingly begun to shift their focus to rare diseases. In academia, advances in genetics analyses and disease mechanisms have allowed scientific understanding to mature, but the lack of funding and translational capability severely limits the rare disease research that leads to clinical trials. Simultaneously, there is a movement towards increased research collaboration, more data sharing, and heightened engagement and active involvement by patients, advocates, and foundations. The growth in networks and social networking tools presents an opportunity to help reach other patients but also find researchers and build collaborations. The growth of collaborative software that can enable researchers to share their data could also enable rare disease patients and foundations to manage their portfolio of funded projects for developing new therapeutics and suggest drug repurposing opportunities. Still there are many thousands of diseases without treatments and with only fragmented research efforts. We will describe some recent progress in several rare diseases used as examples and propose how collaborations could be facilitated. We propose that the development of a center of excellence that integrates and shares informatics resources for rare diseases sponsored by all of the stakeholders would help foster these initiatives.
Full Text Available Left-sided congenital heart disease (CHD encompasses a spectrum of malformations that range from bicuspid aortic valve to hypoplastic left heart syndrome. It contributes significantly to infant mortality and has serious implications in adult cardiology. Although left-sided CHD is known to be highly heritable, the underlying genetic determinants are largely unidentified. In this study, we sought to determine the impact of structural genomic variation on left-sided CHD and compared multiplex families (464 individuals with 174 affecteds (37.5% in 59 multiplex families and 8 trios to 1,582 well-phenotyped controls. 73 unique inherited or de novo CNVs in 54 individuals were identified in the left-sided CHD cohort. After stringent filtering, our gene inventory reveals 25 new candidates for LS-CHD pathogenesis, such as SMC1A, MFAP4, and CTHRC1, and overlaps with several known syndromic loci. Conservative estimation examining the overlap of the prioritized gene content with CNVs present only in affected individuals in our cohort implies a strong effect for unique CNVs in at least 10% of left-sided CHD cases. Enrichment testing of gene content in all identified CNVs showed a significant association with angiogenesis. In this first family-based CNV study of left-sided CHD, we found that both co-segregating and de novo events associate with disease in a complex fashion at structural genomic level. Often viewed as an anatomically circumscript disease, a subset of left-sided CHD may in fact reflect more general genetic perturbations of angiogenesis and/or vascular biology.
Laurberg, Peter Thaysen; Weinreich, Ulla M Øller
A 19-year-old woman with a history of juvenile laryngeal papillomatosis (JLP), treated since childhood with multiple resections, was admitted with symptoms of pneumonia. A chest X-ray and CAT-scan revealed multiple lung cysts and a bronchoalveolar lavage detected human papilloma virus 11. The patient responded well to antibiotics. A body plethysmography showed small lung volumes and low diffusion capacity for carbon monoxide, but normal volume diffusion capacity divided by alveolar volume. Pulmonary cystic disease should be considered when patients with JLP have symptoms of pneumonia.
Brewer, Helen M; Eatough, Virginia; Smith, Jonathan A; Stanley, Cath A; Glendinning, Neil W; Quarrell, Oliver W J
There has been little research into the impact of Juvenile Huntington's Disease (JHD) on the family, and the issues facing this group are poorly understood. The study reported here is part of larger project that aimed to address this. Ten semi-structured interviews with the main carer were carried out, and were analysed using Interpretative Phenomenological Analysis (IPA). This article reports three themes arising from the study relating to the psychosocial impact of JHD on the family: (1) dealing with something so different; (2) lack of understanding (3) isolation. This information is useful in developing appropriate services for families affected by JHD, as well as being of relevance to other childhood conditions.
Full Text Available A 50-year-old female presented with fever, symmetrical arthralgias, rash, painful oral ulcerations and alopecia since 8 weeks. Examination showed mild hepatospleenomegaly. Investigations revealed leucocytosis, neutrophilia, elevated sedimentation rate and raised ferritin levels (3850 ng/ml. Computerized tomography (CT abdomen showed hepatospleenomegaly, mild ascitis and mild bilateral pleural-effusion. After ruling out occult infections, tuberculosis, malignancies and autoimmune diseases by appropriate investigations, and due to raised ferritin levels, adult onset stills disease (AOSD was diagnosed. Patient responded to oral steroids initially, but after 7 days developed severe abdominal pain. Repeat CT showed multiple enlarged, necrotic and matted retroperitoneal lymph nodes with caseating granuloma on histopathology suggesting tuberculosis. Patient was given four-drug anti-tubercular treatment and she improved. Thus our patient of occult abdominal tuberculosis with reactive arthritis (Poncet′s disease presented with hyperferritinemia mimicking AOSD. We postulate that extreme hyperferritinemia can be seen in tuberculosis and tuberculosis must be conclusively ruled out before diagnosing AOSD in tropics.
Full Text Available ABSTRACT: Potter's sequence is more appropriate terminology than potter facies, since not every individual with this syndrome has exactly the same set of symptoms and signs but they share a common chain of events triggered by differe nt causes, leading to the same endpoint of reduced or absent amniotic fluid. It has a charact eristic facial appearance associated with other abnormalities as Ophthalmic(Cataract, Cardiovascula r (Ventricular septal defect. Fallot's tetralogy, Patent ductus arteriosus, and muscu loskeletal (Clubbed feet, Sacral agenesis . Here we are presenting two cases of potter sequence due to polycystic kidney disease ( type-i in association with other congenital anomalies ( ab sence of left diaphragm ,pericardial effusion, pulmonary hypoplasia which is rare and incompatible to life
Hill, E G; Ding, L; Waller, L A
Statistical tests to detect clustering of a rare disease investigate whether an observed spatial pattern of cases appears to be due to chance alone. Heterogeneous population density and the geographic structure of the data under consideration complicate the ability to make comparisons of different tests. Further, interpretation of test results depends on the nature of the test used and what feature of the data it is designed to detect. With these issues in mind, we compare three recent tests for assessing general clustering among cases where the population is distributed heterogeneously across the study area, namely those of Besag and Newell, Turnbull et al. and Tango. We compare these methods using 1981 incidence data for severe cardiac birth defects from Santa Clara County, California.
Valverde, Ana M; Reed, Shelby D; Schulman, Kevin A
The 1983 Orphan Drug Act created incentives for the development of orphan drugs. Despite its successes, including a substantial increase in new drugs, approved orphan drugs still treat fewer than 5 percent of registered rare diseases. In addition, concerns have arisen about the high prices of many of these therapies, which can cost hundreds of thousands of dollars per patient each year. In this article, we propose a new "grant-and-access pathway," in which drug developers could opt to compete for federal grants to subsidize the costs of clinical testing. In return for the grant funding, companies would no longer claim orphan drug tax credits and would agree to price caps for marketed products based on the duration and costs associated with drug development, expected market size, and target rate of return. We identify scenarios in which such a policy could provide a net benefit to society.
Priscila Marques de Macedo
Full Text Available O Dermatomiofibroma está incluído no grupo de lesões neoplásicas mesenquimais benignas de linhagem fibroblástica e miofibroblástica da pele. É uma doença rara, havendo aproximadamente 100 casos descritos na literatura mundial até o momento. Este artigo relata o caso de uma mulher jovem com apresentação clínica típica e diagnóstico histopatológico de dermatomiofibroma. Foram realizadas colorações especiais que mostraram preservação das fibras colágenas e a imunohistoquímica revelou positividade para vimentina e negatividade para actina e S100. Por se tratar de doença rara, os achados histopatológicos são de grande importância, mas a supeição clínica é possível em casos típicos como este.Dermato myofibroma is included in the group of benign cutaneous mesenchymal neoplastic lesions of fibroblastic and myofibroblastic lineage. It's a rare disease and there are approximately only one hundred cases described worldwide in the medical literature up to now. The present study reports the case of a young woman with typical clinical cutaneous lesion and histopathological diagnosis of dermato myofibroma. Special stains were carried out which showed preserved collagen fibers and immunohistochemistry was positive for vimentin and negative for actin and S100. As it is a rare disease, the histopathological findings are of great importance but clinical suspicion is possible in typical cases such as this one.
Full Text Available Abstract Background Computer-based teaching (CBT is a well-known educational device, but it has never been applied systematically to the teaching of a complex, rare, genetic disease, such as Hunter disease (MPS II. Aim To develop interactive teaching software functioning as a virtual clinic for the management of MPS II. Implementation and Results The Hunter disease eClinic, a self-training, user-friendly educational software program, available at the Lysosomal Storage Research Group (http://www.lysosomalstorageresearch.ca, was developed using the Adobe Flash multimedia platform. It was designed to function both to provide a realistic, interactive virtual clinic and instantaneous access to supporting literature on Hunter disease. The Hunter disease eClinic consists of an eBook and an eClinic. The eClinic is the interactive virtual clinic component of the software. Within an environment resembling a real clinic, the trainee is instructed to perform a medical history, to examine the patient, and to order appropriate investigation. The program provides clinical data derived from the management of actual patients with Hunter disease. The eBook provides instantaneous, electronic access to a vast collection of reference information to provide detailed background clinical and basic science, including relevant biochemistry, physiology, and genetics. In the eClinic, the trainee is presented with quizzes designed to provide immediate feedback on both trainee effectiveness and efficiency. User feedback on the merits of the program was collected at several seminars and formal clinical rounds at several medical centres, primarily in Canada. In addition, online usage statistics were documented for a 2-year period. Feedback was consistently positive and confirmed the practical benefit of the program. The online English-language version is accessed daily by users from all over the world; a Japanese translation of the program is also available. Conclusions The
A 32-year-old female presented with 5-year history ofiron deficiency anemia, marked pallor and edema ofboth lower limbs. Laboratory investigations includingcomplete blood count, blood film, iron studies, lipidprofile, ascitic fluid analysis, test of stool for occult bloodand alpha 1 anti-trypsin. Upper, lower gastrointestinal（GIT） endoscopies, and enteroscopy were performed.Imaging techniques as abdominal ultrasonography andcomputed tomography were done. Echocardiography,lymph node biopsy and bone marrow examinationwere normal. The case was diagnosed as Waldmann＇s disease with protein losing enteropathy and recurrentGIT bleeding. Management started with low fat diet withmedium chain triglyceride, octreotide 200 μg twice a day,tranexamic acid and blood transfusion. Then, exploratorylaparotomy with pathological examination of resectedsegment was done when recurrent GIT bleeding occurredand to excluded malignant transformation.
Zanoni, Paolo; Khetarpal, Sumeet A; Larach, Daniel B;
Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL......-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss......-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from...
Full Text Available Pathogenic mutations in APP, PSEN1, PSEN2, MAPT and GRN have previously been linked to familial early onset forms of dementia. Mutation screening in these genes has been performed in either very small series or in single families with late onset AD (LOAD. Similarly, studies in single families have reported mutations in MAPT and GRN associated with clinical AD but no systematic screen of a large dataset has been performed to determine how frequently this occurs. We report sequence data for 439 probands from late-onset AD families with a history of four or more affected individuals. Sixty sequenced individuals (13.7% carried a novel or pathogenic mutation. Eight pathogenic variants, (one each in APP and MAPT, two in PSEN1 and four in GRN three of which are novel, were found in 14 samples. Thirteen additional variants, present in 23 families, did not segregate with disease, but the frequency of these variants is higher in AD cases than controls, indicating that these variants may also modify risk for disease. The frequency of rare variants in these genes in this series is significantly higher than in the 1,000 genome project (p = 5.09 × 10⁻⁵; OR = 2.21; 95%CI = 1.49-3.28 or an unselected population of 12,481 samples (p = 6.82 × 10⁻⁵; OR = 2.19; 95%CI = 1.347-3.26. Rare coding variants in APP, PSEN1 and PSEN2, increase risk for or cause late onset AD. The presence of variants in these genes in LOAD and early-onset AD demonstrates that factors other than the mutation can impact the age at onset and penetrance of at least some variants associated with AD. MAPT and GRN mutations can be found in clinical series of AD most likely due to misdiagnosis. This study clearly demonstrates that rare variants in these genes could explain an important proportion of genetic heritability of AD, which is not detected by GWAS.
Rare earth dements have unique physical, magnetic, luminescent and catalytic properties. They have been successfully used as medicine and probes in luminescent resonance energy transfer (LRET) for bioassays, as well as reagents for diagnosis in magnetic resonance imaging (MRI). In this progress report, we will focus on recent progress on how rare earth amino complexes bind to DNA and change DNA structure, especially on DNA B-Z transition induced by rare earth amino acid complex and its potential impact on Alzheimer's disease (AD).
Full Text Available Many autoimmune diseases have been reported to be associated with malignancies with an incidence rate of 5%. (1 A 30-year male with recurrent edema of the lips and periorbital area with itching and pain for 6 weeks. He had both extremity weakness with upper back pain for 1 month. H/O loss of weight and appetite for 1 yr. With this clinical picture, a diagnosis of angioedema/dermatomyositis (CTD was suspected. CPK and CPK-MB within normal limits, antinuclear antibodies + by IF with titre of 1:320 with nucleus-granular pattern suggesting autoantibodies against U1-RNP Antigen/Sm Antigen. USG scrotum- a single testes. MRI-spine revealed multiple peripancreatic, pre- and para-aortic and left supraclavicular lymph nodes with nodules in both lungs. CT Thorax and CT Abdomen showed liver and lung metastasis with periportal and vertebral lymph nodes. FNAC left supraclavicular node-positive for malignant cells, suggestive of metastatic malignant germ cell tumor. Tumor markers-elevated (aFP-180, bHCG- 457.2.
Fernando De Maio
Full Text Available Marfan syndrome is caused by mutations in the fibrillin-1 gene (FBN1. The most important features affect the cardiovascular system, eyes, and skeleton. The aim of this study was to report the most frequent musculoskeletal alterations observed in 146 patients affected by Marfan syndrome. Fifty-four patients (37% underwent cardiac surgery and 11 of them received emergent surgery for acute aortic dissection. Ectopia lentis was found in 68 patients (47% whereas myopia above 3D occurred in 46 patients (32%. Musculoskeletal anomalies were observed in all patients with Marfan syndrome. In 88 patients (60.2%, the associated “wrist and thumb sign” was present; in 58 patients (39.7%, pectus carinatum deformity; in 44 patients (30.1%, pectus excavatum; in 49 patients (33.5%, severe flatfoot; in 31 patients (21.2%, hindfoot deformity; in 54 patients (36.9%, reduced US/LS ratio or increased arm span-height ratio; in 37 patients (25.3%, scoliosis or thoracolumbar kyphosis; in 22 patients (15%, reduced elbow extension (170° or less. Acetabular protrusion was ascertained on radiographs in 27 patients (18.4%. Orthopaedic aspects of the disease are very important for an early diagnosis; however, we have not observed definite correlations between the extent of orthopaedic involvement and aortic complications.
Fichera, Alessandro; De Luna, Vincenzo; Mancini, Federico; Caterini, Roberto
Marfan syndrome is caused by mutations in the fibrillin-1 gene (FBN1). The most important features affect the cardiovascular system, eyes, and skeleton. The aim of this study was to report the most frequent musculoskeletal alterations observed in 146 patients affected by Marfan syndrome. Fifty-four patients (37%) underwent cardiac surgery and 11 of them received emergent surgery for acute aortic dissection. Ectopia lentis was found in 68 patients (47%) whereas myopia above 3D occurred in 46 patients (32%). Musculoskeletal anomalies were observed in all patients with Marfan syndrome. In 88 patients (60.2%), the associated “wrist and thumb sign” was present; in 58 patients (39.7%), pectus carinatum deformity; in 44 patients (30.1%), pectus excavatum; in 49 patients (33.5%), severe flatfoot; in 31 patients (21.2%), hindfoot deformity; in 54 patients (36.9%), reduced US/LS ratio or increased arm span-height ratio; in 37 patients (25.3%), scoliosis or thoracolumbar kyphosis; in 22 patients (15%), reduced elbow extension (170° or less). Acetabular protrusion was ascertained on radiographs in 27 patients (18.4%). Orthopaedic aspects of the disease are very important for an early diagnosis; however, we have not observed definite correlations between the extent of orthopaedic involvement and aortic complications. PMID:28050285