Orphanet Journal of Rare Diseases

http://www.ojrd.com/

List of Papers (Total 1,436)

Lucerastat, an iminosugar with potential as substrate reduction therapy for glycolipid storage disorders: safety, tolerability, and pharmacokinetics in healthy subjects

Background Lucerastat, an inhibitor of glucosylceramide synthase, has the potential to restore the balance between synthesis and degradation of glycosphingolipids in glycolipid storage disorders such as Gaucher disease and Fabry disease. The safety, tolerability, and pharmacokinetics of oral lucerastat were evaluated in two separate randomized, double-blind, placebo-controlled, ...

Fatal anaphylaxis registries data support changes in the who anaphylaxis mortality coding rules

Anaphylaxis is defined as a severe life-threatening generalized or systemic hypersensitivity reaction. The difficulty of coding anaphylaxis fatalities under the World Health Organization (WHO) International Classification of Diseases (ICD) system is recognized as an important reason for under-notification of anaphylaxis deaths. On current death certificates, a limited number of ICD ...

Clinical, biochemical and molecular characteristics of Filipino patients with mucopolysaccharidosis type II - Hunter syndrome

Background Mucopolysaccharidosis type II, an X-linked recessive disorder is the most common lysosomal storage disease detected among Filipinos. This is a case series involving 23 male Filipino patients confirmed to have Hunter syndrome. The clinical and biochemical characteristics were obtained and mutation testing of the IDS gene was done on the probands and their female ...

FOXN1 deficient nude severe combined immunodeficiency

Nude severe combined immunodeficiency is a rare inherited disease caused by autosomal recessive loss-of-function mutations in FOXN1. This gene encodes a transcription factor essential for the development of the thymus, the primary lymphoid organ that supports T-cell development and selection. To date nine cases have been reported presenting with the clinical triad of absent thymus ...

Glucocorticoid receptor gene polymorphisms in hereditary angioedema with C1-inhibitor deficiency

Background Hereditary angioedema caused by C1-inhibitor deficiency (C1-INH-HAE) is a rare, autosomal dominant disorder. C1-INH-HAE is characterized by edema–formation, which may occur in response to stress. The individual’s response to stress stimuli is partly genetically determined. Activation of the hypothalamic–pituitary–adrenal axis results in the release of cortisol. In turn, ...

Moebius sequence –a multidisciplinary clinical approach

Background Moebius Sequence (MS) is a rare disorder defined by bilateral congenital paralysis of the abducens and facial nerves in combination with various odontological, craniofacial, ophthalmological and orthopaedic conditions. The aetiology is still unknown; but both genetic (de novo mutations) and vascular events in utero are reported. The purpose of present study was through a ...

TuberOus SClerosis registry to increase disease Awareness (TOSCA) – baseline data on 2093 patients

Background Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder. Many gaps remain in the understanding of TSC because of the complexity in clinical presentation. The TuberOus SClerosis registry to increase disease Awareness (TOSCA) is an international disease registry designed to address knowledge gaps in the natural history and management of TSC. Here, we ...

Update on Lysinuric Protein Intolerance, a Multi-faceted Disease Retrospective cohort analysis from birth to adulthood

Background Lysinuric protein intolerance (LPI) is a rare metabolic disease resulting from recessive-inherited mutations in the SLC7A7 gene encoding the cationic amino-acids transporter subunit y + LAT1. The disease is characterised by protein-rich food intolerance with secondary urea cycle disorder, but symptoms are heterogeneous ranging from infiltrative lung disease, kidney ...

Ethical imperatives of timely access to orphan drugs: is possible to reconcile economic incentives and patients’ health needs?

Background More than 6,800 rare diseases and conditions have been identified in the US, which affect 25–30 million Americans. In 1983, the US Congress enacted the Orphan Drug Act (ODA) to encourage the development and marketing of drugs to treat rare diseases and conditions. This study analyzed all orphan designations and FDA approvals since 1983 through 2015, discussed the ...

Chronic Infantile Neurological Cutaneous and Articular (CINCA) syndrome: a review

Introduction The Chronic Infantile Neurological Cutaneous and Articular (CINCA, or Neonatal-onset multisystem inflammatory disease NOMID) is a rare autoinflammatory disease identified in 1987 by Prieur et al., typically characterized by the triad of skin rash, arthropathy and central nervous system manifestations. It represents the most severe phenotype of the cryopyrin-associated ...

Experiences of caregivers of children with inherited metabolic diseases: a qualitative study

Background We sought to understand the experiences of parents/caregivers of children with inherited metabolic diseases (IMD) in order to inform strategies for supporting patients and their families. We investigated their experiences regarding the management of disease, its impact on child and family life, and interactions with the health care system. Methods From four Canadian ...

Cytotoxic edema and diffusion restriction as an early pathoradiologic marker in canavan disease: case report and review of the literature

Background Canavan disease is a devastating autosomal recessive leukodystrophy leading to spongiform degeneration of the white matter. There is no cure or treatment for Canavan disease, and disease progression is poorly understood. Results We report a new presentation of a patient found to have Canavan disease; brain magnetic resonance imaging (MRI) revealed white matter cytotoxic ...

Abnormal pelvic morphology and high cervical length are responsible for high-risk pregnancies in women displaying achondroplasia

Pregnancies of women displaying achondroplasia are at high risk of adverse events. Early sonographic assessment of affected women can indicate an unusually long cervical length. It is the consequence of pathological anatomy of the pelvis. Thus, there is a foreseeable dystocia owing to cephalopelvic disproportion. Furthermore, this situation could also complicate cervical ripening ...

Familial vs. sporadic sarcoidosis: BTNL2 polymorphisms, clinical presentations, and outcomes in a French cohort

Background The occurrence of familial forms of sarcoidosis (OMIM 181100) suggests a genetic predisposition. The involvement of butyrophilin-like 2 (BTNL2) gene (rs2076530 variant) has to be investigated. Results The study performed independent analyses of BTNL2 polymorphism, clinical phenotypes, and outcomes in familial vs. sporadic presentations in 256 sporadic and 207 familial ...

Aspartylglycosaminuria: a review

Aspartylglucosaminuria (AGU), a recessively inherited lysosomal storage disease, is the most common disorder of glycoprotein degradation with a high prevalence in the Finnish population. It is a lifelong condition affecting on the patient’s appearance, cognition, adaptive skills, physical growth, personality, body structure, and health. An infantile growth spurt and development of ...

Conservatively treated Congenital Hyperinsulinism (CHI) due to K-ATP channel gene mutations: reducing severity over time

Background Patients with Congenital Hyperinsulinism (CHI) due to mutations in K-ATP channel genes (K-ATP CHI) are increasingly treated by conservative medical therapy without pancreatic surgery. However, the natural history of medically treated K-ATP CHI has not been described; it is unclear if the severity of recessively and dominantly inherited K-ATP CHI reduces over time. We ...

Fostering collaborative research for rare genetic disease: the example of niemann-pick type C disease

Rare disease represents one of the most significant issues facing the medical community and health care providers worldwide, yet the majority of these disorders never emerge from their obscurity, drawing little attention from the medical community or the pharmaceutical industry. The challenge therefore is how best to mobilize rare disease stakeholders to enhance basic, ...

Health-related quality of life and a cost-utility simulation of adults in the UK with osteogenesis imperfecta, X-linked hypophosphatemia and fibrous dysplasia

Background Health-related quality of life of adults with osteogenesis imperfecta (OI), fibrous dysplasia (FD) and X-linked hypophosphatemia (XLH) remains poorly described. The aim of this study was to describe the HRQoL of adults with osteogenesis imperfecta, fibrous dysplasia and X-linked hypophophataemia and perform a cost-utility simulation to calculate the maximum cost that a ...

Ataxia telangiectasia: a review

Definition of the disease Ataxia telangiectasia (A-T) is an autosomal recessive disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. A-T is often referred to as a genome instability or DNA damage response syndrome. Epidemiology The world-wide prevalence of A-T is estimated to be between 1 in ...

Rett syndrome – biological pathways leading from MECP2 to disorder phenotypes

Rett syndrome (RTT) is a rare disease but still one of the most abundant causes for intellectual disability in females. Typical symptoms are onset at month 6–18 after normal pre- and postnatal development, loss of acquired skills and severe intellectual disability. The type and severity of symptoms are individually highly different. A single mutation in one gene, coding for ...

20-year follow-up study of Danish HHT patients—survival and causes of death

Background Hereditary Haemorrhagic Telangiectasia (HHT) is a dominantly inheritable disorder, with a wide variety of clinical manifestations due to presence of multiple arteriovenous manifestations. The most common mutations are found in HHT1 (ENG) and HHT2 (ACVRL1) patients, causing alterations in the TGF-β pathway which is responsible for angiogenesis. Modulations of angiogenesis ...

Symmetrical acrokeratoderma: a case series in Indian patients

Symmetrical acrokeratoderma is a recently described dermatosis in young adult males of Chinese descent. In this report, we describe a series of five cases of symmetrical acrokeratoderma from India. All 5 patients had asymptomatic, brownish-black plaques distributed symmetrically over dorsum of hand and feet with variable involvement of wrist, flexural surface of forearm, elbow, ...

Current models of care for disorders of sex development – results from an International survey of specialist centres

Background To explore the current models of practice in centres delivering specialist care for children with disorders of sex development (DSD), an international survey of 124 clinicians, identified through DSDnet and the I-DSD Registry, was performed in the last quarter of 2014. Results A total of 78 (63 %) clinicians, in 75 centres, from 38 countries responded to the survey. A ...

An innovative and collaborative partnership between patients with rare disease and industry-supported registries: the Global aHUS Registry

Background Patients are becoming increasingly involved in research which can promote innovation through novel ideas, support patient-centred actions, and facilitate drug development. For rare diseases, registries that collect data from patients can increase knowledge of the disease’s natural history, evaluate clinical therapies, monitor drug safety, and measure quality of care. The ...

Treatment management during the adolescent transition period of girls and young women with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS): a systematic literature review

Introduction In health services research, there is a special emphasis on the transition from adolescence into adulthood. During this transition period, adolescents change from pediatric to adult medical care. This process must be carefully structured, particularly when special medical care is required. Challenges and difficulties become apparent particularly in the case of rare ...