1,648 results match your criteria Orphanet Journal of Rare Diseases [Journal]


Comorbidity among HHT patients and their controls in a 20 years follow-up period.

Orphanet J Rare Dis 2018 Dec 14;13(1):223. Epub 2018 Dec 14.

Odense Patient data Explorative Network (OPEN), Odense University Hospital/Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

Background: Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant genetic disorder with a wide variety of clinical manifestations due to the presence of multiple arteriovenous malformations in various tissues and organs.

Objective: To study the need for hospital admittance in a group of HHT patients and matched controls during a 20 years follow-up period commencing in 1995.

Methods: All HHT patients in the County of Funen, Denmark, were included. Read More

View Article
December 2018

Air travel and incidence of pneumothorax in lymphangioleiomyomatosis.

Orphanet J Rare Dis 2018 Dec 13;13(1):222. Epub 2018 Dec 13.

Service de pneumologie, Centre hospitalier universitaire vaudois, PMU BU44.07, Rue du Bugnon 44, 1011, Lausanne, Switzerland.

Background: Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease of women characterized by multiple lung cysts leading to respiratory insufficiency and frequent pneumothorax (PT). Air travel (AT) could increase the risk of PT in LAM through rupture of subpleural cysts induced by atmospheric pressure changes in aircraft cabin. To determine whether AT increases the risk of PT in LAM, we performed a retrospective survey of members of European LAM patient associations. Read More

View Article
December 2018

Novel CHM mutations in Polish patients with choroideremia - an orphan disease with close perspective of treatment.

Orphanet J Rare Dis 2018 Dec 12;13(1):221. Epub 2018 Dec 12.

Department of Medical Genetics, Poznan University of Medical Sciences, 8, Rokietnicka St, 60-806, Poznan, Poland.

Background: Choroideremia (CHM) is a rare X-linked recessive retinal dystrophy characterized by progressive chorioretinal degeneration in the males affected. The symptoms include night blindness in childhood, progressive peripheral vision loss and total blindness in the late stages. The disease is caused by mutations in the CHM gene encoding Rab Escort Protein 1 (REP-1). Read More

View Article
December 2018

Hyperammonaemia in classic organic acidaemias: a review of the literature and two case histories.

Orphanet J Rare Dis 2018 Dec 6;13(1):219. Epub 2018 Dec 6.

Department of Pediatrics, Division of Medical Genetics, University of Utah School of Medicine, 30 N 1900 E, Salt Lake City, UT, 84132, USA.

Background: The 'classic' organic acidaemias (OAs) (propionic, methylmalonic and isovaleric) typically present in neonates or infants as acute metabolic decompensation with encephalopathy. This is frequently accompanied by severe hyperammonaemia and constitutes a metabolic emergency, as increased ammonia levels and accumulating toxic metabolites are associated with life-threatening neurological complications. Repeated and frequent episodes of hyperammonaemia (alongside metabolic decompensations) can result in impaired growth and intellectual disability, the severity of which increase with longer duration of hyperammonaemia. Read More

View Article
December 2018

Determining the value contribution of selexipag for the treatment of pulmonary arterial hypertension (PAH) in Spain using reflective multi-criteria decision analysis (MCDA).

Orphanet J Rare Dis 2018 Dec 10;13(1):220. Epub 2018 Dec 10.

Omakase Consulting S.L., Madrid, Spain.

Background: Pulmonary Arterial Hypertension (PAH) is a chronic rare disease that can lead to serious cardiovascular problems and death. Additional treatments that increase effectiveness, that are safe and with a convenient administration that improve outcomes and quality of life for patients are needed. The aim of this study was to assess the value contribution of the new, oral prostacyclin receptor agonist, selexipag, for PAH treatment in Spain through reflective Multicriteria Decision Analysis (MCDA) methodology. Read More

View Article
December 2018

Combined surgical-orthodontic treatment of patients with cleidocranial dysplasia: case report and review of the literature.

Orphanet J Rare Dis 2018 Dec 4;13(1):217. Epub 2018 Dec 4.

Department of Oral and Craniomaxillofacial Science, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No 500, Quxi Road, Shanghai, Shanghai, China.

Objectives: To study the present treatment situation and investigate a better orthodontic approach for patients with cleidocranial dysplasia (CCD) through systematically reviewing the published cases and to conclude the surgical-orthodontic treatment experience of cleidocranial dysplasia.

Methods: A comprehensive search for studies published through to April 10, 2018 was conducted using the Pubmed, Web of Science, and Embase databases. The CCD cases treated with the approach combining surgical exposure and orthodontic treatment were concluded. Read More

View Article
December 2018

The French National Registry of patients with Facioscapulohumeral muscular dystrophy.

Orphanet J Rare Dis 2018 Dec 4;13(1):218. Epub 2018 Dec 4.

Aix Marseille Univ, INSERM, MMG, Bioinformatics & Genetics, Marseille, France.

Background: Facioscapulohumeral muscular dystrophy is a rare inherited neuromuscular disease with an estimated prevalence of 1/20,000 and France therefore harbors about 3000 FSHD patients. With research progress and the development of targeted therapies, patients' identification through registries can facilitate and improve recruitment in clinical trials and studies.

Results: The French National Registry of FSHD patients was designed as a mixed model registry involving both patients and physicians, through self-report and clinical evaluation questionnaires respectively, to collect molecular and clinical data. Read More

View Article
December 2018
1 Read

Latitudinal differences on the global epidemiology of infantile spasms: systematic review and meta-analysis.

Orphanet J Rare Dis 2018 Nov 29;13(1):216. Epub 2018 Nov 29.

Department of Pediatrics, Division of Neurology, University of Toronto, Toronto, Canada.

Background: Infantile spasms represent the catastrophic, age-specific seizure type associated with acute and long-term neurological morbidity. However, due to rarity and heterogenous determination, there is persistent uncertainty of its pathophysiological and epidemiological characteristics. The purpose of the current study was to address a historically suspected latitudinal basis of infantile spasms incidence, and to interrogate a geographical basis of epidemiology, including the roles of latitude and other environmental factors, using meta-analytic and -regression methods. Read More

View Article
November 2018
2 Reads

Oncologic orphan drugs approved in the EU - do clinical trial data correspond with real-world effectiveness?

Orphanet J Rare Dis 2018 Nov 28;13(1):214. Epub 2018 Nov 28.

College ter Beoordeling Geneesmiddelen/ Dutch Medicines Evaluation Board, Utrecht, the Netherlands.

Background: Evaluation of evidence for efficacy of orphan medicinal products (OMPs) for rare malignancies may be hampered by the use of tumor measurements instead of clinical endpoints. This may cause efficacy data to not always match effectiveness in the real-world. We investigated whether an efficacy-effectiveness gap exists for oncologic OMPs and aimed to identify which factors contribute to it. Read More

View Article
November 2018
1 Read

Patient and observer reported outcome measures to evaluate health-related quality of life in inherited metabolic diseases: a scoping review.

Orphanet J Rare Dis 2018 Nov 28;13(1):215. Epub 2018 Nov 28.

Portuguese Association for Congenital Disorders of Glycosylation (CDG), Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal.

Background: Health-related Quality of Life (HrQoL) is a multidimensional measure, which has gained clinical and social relevance. Implementation of a patient-centred approach to both clinical research and care settings, has increased the recognition of patient and/or observer reported outcome measures (PROMs or ObsROMs) as informative and reliable tools for HrQoL assessment. Inherited Metabolic Diseases (IMDs) are a group of heterogeneous conditions with phenotypes ranging from mild to severe and mostly lacking effective therapies. Read More

View Article
November 2018

Immune cell phenotype and functional defects in Netherton syndrome.

Orphanet J Rare Dis 2018 Nov 26;13(1):213. Epub 2018 Nov 26.

Department of Dermatology and Allergology, Helsinki University Hospital and University of Helsinki, P.O.Box 160, FI-00029 HUS, Helsinki, Finland.

Background: Netherton syndrome (NS) is a rare life-threatening syndrome caused by SPINK5 mutations leading to a skin barrier defect and a severe atopic diathesis. NS patients are prone to bacterial infections, but the understanding of the underlying immune deficiency is incomplete.

Results: We analyzed blood lymphocyte phenotypes and function in relation to clinical infections in 11 Finnish NS patients, aged 3 to 17 years, and healthy age-matched controls. Read More

View Article
November 2018
5 Reads

A nomenclature and classification for the congenital myasthenic syndromes: preparing for FAIR data in the genomic era.

Orphanet J Rare Dis 2018 Nov 26;13(1):211. Epub 2018 Nov 26.

Children's Hospital of Eastern Ontario (CHEO) Research Institute, University of Ottawa, Ottawa, ON, K1H 8L1, Canada.

Background: Congenital myasthenic syndromes (CMS) are a heterogeneous group of inherited neuromuscular disorders sharing the common feature of fatigable weakness due to defective neuromuscular transmission. Despite rapidly increasing knowledge about the genetic origins, specific features and potential treatments for the known CMS entities, the lack of standardized classification at the most granular level has hindered the implementation of computer-based systems for knowledge capture and reuse. Where individual clinical or genetic entities do not exist in disease coding systems, they are often invisible in clinical records and inadequately annotated in information systems, and features that apply to one disease but not another cannot be adequately differentiated. Read More

View Article
November 2018

Arginine does not rescue p.Q188R mutation deleterious effect in classic galactosemia.

Orphanet J Rare Dis 2018 Nov 26;13(1):212. Epub 2018 Nov 26.

Department of Clinical Genetics, Maastricht University Medical Center +, Maastricht, The Netherlands.

Background: Classic galactosemia is a rare genetic metabolic disease with an unmet treatment need. Current standard of care fails to prevent chronically-debilitating brain and gonadal complications. Many mutations in the GALT gene responsible for classic galactosemia have been described to give rise to variants with conformational abnormalities. Read More

View Article
November 2018
2 Reads

A retrospective analysis of health care utilization for patients with mitochondrial disease in the United States: 2008-2015.

Orphanet J Rare Dis 2018 Nov 22;13(1):210. Epub 2018 Nov 22.

Massachusetts General Hospital, Boston, MA, USA.

Background: Mitochondrial disease (MD) is a heterogeneous group of disorders characterized by impaired energy production caused by abnormal oxidative phosphorylation. Diagnosis of MD is challenging given the variability in how the disease can affect an individual's neurologic, cardiovascular, ophthalmologic, or gastroenterological systems. This study describes the health care utilization and cost in patients diagnosed with MD. Read More

View Article
November 2018
3 Reads

Early detection of median nerve compression by Electroneurography can improve outcome in children with Mucopolysaccharidoses.

Orphanet J Rare Dis 2018 Nov 21;13(1):209. Epub 2018 Nov 21.

Department of Pediatric Neurology, CHU Trousseau, APHP, Paris, France.

Background: Carpal tunnel syndrome (CTS) is a common complication of the mucopolysaccharidoses. In severe or attenuated mucopolysaccharidoses patients, clinical symptoms of CTS usually appear at a late stage of median nerve compression. Relying on CTS symptoms is often too late and there is a risk of axonal damage and further irreversible sequelae. Read More

View Article
November 2018
1 Read

Survey on patients with undiagnosed diseases in Japan: potential patient numbers benefiting from Japan's initiative on rare and undiagnosed diseases (IRUD).

Orphanet J Rare Dis 2018 Nov 20;13(1):208. Epub 2018 Nov 20.

Japan Agency for Medical Research and Development (AMED), 22F Yomiuri Shimbun Bldg., 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan.

Background: There is now an international partnership to establish global programs for patients with rare and undiagnosed diseases, involving interdisciplinary expert panels and phenotype-driven genetic analyses utilizing next-generation sequencing and analytics. Whereas it is crucial to have data such as the actual number of undiagnosed patients, to help inform the implementation plan with such programs, there have been no systematic studies to quantitate the numbers of patients principally because of the inherent difficulty in most health systems to identify patients whose condition has not yet been diagnosed and coded. Our national experience with a rare disease program, Nan-Byo which was established in 1972, and the more recently expanded Initiative on Rare and Undiagnosed Diseases (IRUD), provided a unique opportunity to design a cross-sectional study to ascertain the undiagnosed patients in Japan based on the IRUD referral criteria. Read More

View Article
November 2018
1 Read

Gynecologic assessment of 19 adult females with cartilage-hair hypoplasia - high rate of HPV positivity.

Orphanet J Rare Dis 2018 Nov 16;13(1):207. Epub 2018 Nov 16.

Children's Hospital, Pediatric Research Center, HUS Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Background: Patients with cartilage-hair hypoplasia (CHH), a rare metaphyseal chondrodysplasia, manifest severe growth failure, variable immunodeficiency and increased risk of malignancies. The impact of CHH on gynecologic and reproductive health is unknown. Vulnerability to genital infections may predispose CHH patients to prolonged human papillomavirus (HPV) infections potentially leading to cervical, vaginal and vulvar cancer. Read More

View Article
November 2018
3 Reads

Evidence supporting regulatory-decision making on orphan medicinal products authorisation in Europe: methodological uncertainties.

Orphanet J Rare Dis 2018 Nov 15;13(1):206. Epub 2018 Nov 15.

Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, 08193, Bellaterra, Barcelona, Spain.

Background: To assess uncertainty in regulatory decision-making for orphan medicinal products (OMP), a summary of the current basis for approval is required; a systematic grouping of medical conditions may be useful in summarizing information and issuing recommendations for practice.

Methods: A grouping of medical conditions with similar characteristics regarding the potential applicability of methods and designs was created using a consensus approach. The 125 dossiers for authorised OMP published between 1999 and 2014 on the EMA webpage were grouped accordingly and data was extracted from European Public Assessment Reports (EPARs) to assess the extent and robustness of the pivotal evidence supporting regulatory decisions. Read More

View Article
November 2018
3 Reads

Cognitive DDx Assistant in Rare Diseases.

Conf Proc IEEE Eng Med Biol Soc 2018 Jul;2018:3244-3247

There are between 6,000 - 7,000 known rare diseases today. Identifying and diagnosing a patient with rare disease is time consuming, cumbersome, cost intensive and requires resources generally available only at large hospital centers. Furthermore, most medical doctors, especially general practitioners, will likely only see one patient with a rare disease if at all. Read More

View Article
July 2018
3 Reads

Multiple endocrine neoplasia type 1: extensive analysis of a large database of Florentine patients.

Orphanet J Rare Dis 2018 Nov 14;13(1):205. Epub 2018 Nov 14.

Department of Surgery and Translational Medicine, University of Florence, Largo Palagi 1, 50139, Florence, Italy.

Background: Multiple endocrine neoplasia (MEN1) is a rare inherited multi-tumour syndrome, affecting specific neuroendocrine organs and non-endocrine tissues with a variable spectrum of over 20 possible different combinations, caused by inactivating heterozygote mutations of the MEN1 gene. Disease onset, penetrance, clinical presentation, course and prognosis are all extremely variable, even among individuals bearing the same causative mutation, which doesn't allow prediction of the individual clinical phenotype (based on the specific result of the genetic test), thus compelling all patients and mutation carriers to undergo a common routine general screening program.

Results: We performed an extensive epidemiological, clinical and genetic analysis of the Florentine MEN1 patient database, which includes 145 MEN1 patients and 20 asymptomatic MEN1 carriers, constantly followed up at the Regional Referral Centre for Inherited Endocrine Tumours of the Tuscany Region, during the last three decades. Read More

View Article
November 2018
3 Reads

Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis.

Orphanet J Rare Dis 2018 Nov 14;13(1):204. Epub 2018 Nov 14.

Departments of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea.

Background: Lymphangioleiomyomatosis is a rare disease caused by unregulated activation of mammalian target of rapamycin (mTOR) signalling pathway. Sirolimus showed efficacy in a phase 3 trial of patients with lymphangioleiomyomatosis, but the optimal dose remains unclear.

Methods: We investigated the efficacy and safety of low-dose compared with conventional-dose sirolimus. Read More

View Article
November 2018
3 Reads

Fear of disease progression in carriers of the m.3243A > G mutation.

Orphanet J Rare Dis 2018 Nov 13;13(1):203. Epub 2018 Nov 13.

Department of Medical Psychology, Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 10, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.

Background: Being diagnosed with mitochondrial disease due to the m.3243A > G mutation is frequently preceded by a long diagnostic process. The disease itself is characterized by heterogeneous course and expression, so leaving patients with considerable uncertainty regarding their prognosis and treatment possibilities. Read More

View Article
November 2018

The burden of common variable immunodeficiency disorders: a retrospective analysis of the European Society for Immunodeficiency (ESID) registry data.

Orphanet J Rare Dis 2018 Nov 12;13(1):201. Epub 2018 Nov 12.

Department Tranzo, Tilburg University, PO Box 90153 (RP219), 5000 LE, Tilburg, the Netherlands.

Background: Common variable immunodeficiency disorders (CVID) are a group of rare innate disorders characterized by specific antibody deficiency and increased rates of infections, comorbidities and mortality. The burden of CVID in Europe has not been previously estimated. We performed a retrospective analysis of the European Society for Immunodeficiencies (ESID) registry data on the subset of patients classified by their immunologist as CVID and treated between 2004 and 2014. Read More

View Article
November 2018
1 Read

Applicability and added value of novel methods to improve drug development in rare diseases.

Orphanet J Rare Dis 2018 Nov 12;13(1):200. Epub 2018 Nov 12.

Clinical Trial Methodology, Julius Center for Health Sciences and Primary Care, Biostatistics and Research Support, University Medical Center Utrecht, University of Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands.

Background: The ASTERIX project developed a number of novel methods suited to study small populations. The objective of this exercise was to evaluate the applicability and added value of novel methods to improve drug development in small populations, using real world drug development programmes as reported in European Public Assessment Reports.

Methods: The applicability and added value of thirteen novel methods developed within ASTERIX were evaluated using data from 26 European Public Assessment Reports (EPARs) for orphan medicinal products, representative of rare medical conditions as predefined through six clusters. Read More

View Article
November 2018
4 Reads
3.360 Impact Factor

Impact of biobanks on research outcomes in rare diseases: a systematic review.

Orphanet J Rare Dis 2018 Nov 12;13(1):202. Epub 2018 Nov 12.

School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, Perth, WA, 6027, Australia.

Background: Alleviating the burden of rare diseases requires research into new diagnostic and therapeutic strategies. We undertook a systematic review to identify and compare the impact of stand-alone registries, registries with biobanks, and rare disease biobanks on research outcomes in rare diseases.

Methods: A systematic review and meta-aggregation was conducted using the preferred reporting items for systematic reviews and meta-analyses (the PRISMA statement). Read More

View Article
November 2018
5 Reads

Federating patients identities: the case of rare diseases.

Orphanet J Rare Dis 2018 Nov 12;13(1):199. Epub 2018 Nov 12.

Banque Nationale de Données Maladies Rares, Hôpital Necker Enfants Malades, Assistance Publique des Hôpitaux de Paris, Paris, France.

Background: Patient information in rare disease registries is generally collected from numerous data sources, necessitating the data to be federated. In addition, data for research purposes must be de-identified. Transforming nominative data into de-identified data is thus a key issue, while minimizing the number of identity duplicates. Read More

View Article
November 2018
2 Reads

Inhibitor clinical burden of disease: a comparative analysis of the CHESS data.

Orphanet J Rare Dis 2018 Nov 9;13(1):198. Epub 2018 Nov 9.

Shire, Zug, Switzerland.

Background: Patients with hemophilia and inhibitors generally face greater disease burden compared to patients without inhibitors. While raising awareness of relative burden may improve the standard of care for patients with inhibitors, comparative data are sparse. Analyzing data drawn from the Cost of Haemophilia across Europe - a Socioeconomic Survey (CHESS) study, the aim of this study was to compare the clinical burden of disease in patients with severe hemophilia with and without inhibitors. Read More

View Article
November 2018
3 Reads

Mapping health care of rare diseases: the example of epidermolysis bullosa in Germany.

Orphanet J Rare Dis 2018 Nov 8;13(1):197. Epub 2018 Nov 8.

Department of Paediatric Dermatology, Children's Hospital AUF DER BULT, Janusz-Korczak-Allee 12, 30173, Hannover, Germany.

Background: Rare diseases affect approximately 30 million people in the European Union and present a major health issue. Over 1000 rare skin diseases are known, many of which are of genetic origin and manifest in childhood. One of these diseases is epidermolysis bullosa (EB), a genodermatosis presenting with skin fragility and blistering. Read More

View Article
November 2018
2 Reads

The current landscape of European registries for rare endocrine conditions.

Eur J Endocrinol 2018 Nov 1. Epub 2018 Nov 1.

S Ahmed, Developmental Endocrinology Research Group, School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, United Kingdom of Great Britain and Northern Ireland.

Objective: To identify cross-border international registries for rare endocrine conditions that are led from Europe and understand the extent of engagement with these registries within a network of reference centres (RC) for rare endocrine conditions.

Methods: Database search of international registries and a survey of RCs in the European Reference Network for rare endocrine conditions (Endo-ERN) with an overall response rate of 82%.

Results: Of the 42 conditions with orphacodes currently covered within Endo-ERN, international registries exist for 32 (76%). Read More

View Article
November 2018
3 Reads

Recommendations for the design of small population clinical trials.

Orphanet J Rare Dis 2018 Nov 6;13(1):195. Epub 2018 Nov 6.

Statistics and Epidemiology, Warwick Medical School, University of Warwick, Coventry, UK.

Background: Orphan drug development faces numerous challenges, including low disease prevalence, patient population heterogeneity, and strong presence of paediatric patient populations. Consequently, clinical trials for orphan drugs are often smaller than those of non-orphan drugs, and they require the development of efficient trial designs relevant to small populations to gain the most information from the available data. The International Rare Diseases Research Consortium (IRDiRC) is aimed at promoting international collaboration and advance rare diseases research worldwide, and has as one of its goals to contribute to 1000 new therapies for rare diseases. Read More

View Article
November 2018
5 Reads

From scientific discovery to treatments for rare diseases - the view from the National Center for Advancing Translational Sciences - Office of Rare Diseases Research.

Orphanet J Rare Dis 2018 Nov 6;13(1):196. Epub 2018 Nov 6.

NCATS, NIH, Bethesda, MD, USA.

We now live in a time of unprecedented opportunities to turn scientific discoveries into better treatments for the estimated 30 million people in the US living with rare diseases. Despite these scientific advances, more than 90% of rare diseases still lack an effective treatment. New data and genetics technologies have resulted in the first transformational new treatments for a handful of rare diseases. Read More

View Article
November 2018
2 Reads

The European challenges of funding orphan medicinal products.

Orphanet J Rare Dis 2018 Nov 6;13(1):184. Epub 2018 Nov 6.

Institute of Genomic Medicine and Rare Disorders, Semmelweis University, H 1083 Tömő u, Budapest, 25-29, Hungary.

Background: Funding of orphan medicinal products (OMPs) is an increasing challenge in the European Union (EU).

Objectives: To identify the different methods for public funding of OMPs in order to map the availability for rare disease patients, as well as to compare the public expenditures on OMPs in 8 EU member states.

Methods: Information on the reimbursement status of 83 OMPs was collected in 8 countries by distinguishing standard and special reimbursements. Read More

View Article
November 2018
3 Reads

Nerve ultrasound characterizes AMN polyneuropathy as inhomogeneous and focal hypertrophic.

Orphanet J Rare Dis 2018 Nov 3;13(1):194. Epub 2018 Nov 3.

Center for Neurology, and Hertie-Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany.

Objective: High-resolution nerve ultrasound (HRUS) is a painless tool to quickly evaluate peripheral nerve morphology in vivo. This study set out to characterize peripheral nerve involvement in X-linked adrenomyeloneuropathy (AMN) by HRUS.

Methods: Thirteen adults with genetically proven AMN were examined using the Ultrasound pattern sum score (UPSS) to evaluate morphological abnormalities of peripheral nerves, vagal nerves, as well as cervical nerve roots. Read More

View Article
November 2018
7 Reads

Basal pharmacokinetic parameters of topically applied diacerein in pediatric patients with generalized severe epidermolysis bullosa simplex.

Orphanet J Rare Dis 2018 Nov 1;13(1):193. Epub 2018 Nov 1.

EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology, University Hospital of the Paracelsus Medical University Salzburg, Muellner Hauptstrasse 48, 5020, Salzburg, Austria.

Generalized severe epidermolysis bullosa simplex (EBS-gen sev) is caused by mutations within either the KRT5 or KRT14 gene, phenotypically resulting in blistering and wounding of the skin and mucous membranes after minor mechanical friction. In a clinical phase 2/3 trial, diacerein has recently been shown to significantly reduce blister numbers upon topical application. In this study we addressed basic pharmacokinetic parameters of locally applied diacerein in vitro and in vivo. Read More

View Article
November 2018
2 Reads

Cholic acid for primary bile acid synthesis defects: a life-saving therapy allowing a favorable outcome in adulthood.

Orphanet J Rare Dis 2018 Oct 29;13(1):190. Epub 2018 Oct 29.

Pediatric Hepatology and Pediatric Liver Transplantation Unit, National Reference Centre for rare pediatric liver diseases and Filfoie, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Paris, France.

Background: Oral cholic acid (CA) replacement has been shown to be an effective therapy in children with primary bile acid synthesis defects, which are rare and severe genetic liver diseases. To date there has been no report of the effects of this therapy in children reaching adulthood. The aim of the study was to evaluate the long-term effectiveness and safety of CA therapy. Read More

View Article
October 2018
7 Reads

Sirolimus is efficacious in treatment for extensive and/or complex slow-flow vascular malformations: a monocentric prospective phase II study.

Orphanet J Rare Dis 2018 Oct 29;13(1):191. Epub 2018 Oct 29.

Center for Vascular Anomalies, Division of Plastic Surgery, Cliniques universitaires Saint Luc, University of Louvain, 10 avenue Hippocrate, B-1200, Brussels, Belgium.

Background: Extensive and complex vascular malformations often cause chronic pain and severe functional restraint. Conventional treatments, such as surgery and/or sclerotherapy, are rarely curative, underscoring the great need for new therapeutic modalities. Recent preclinical and clinical data demonstrated that sirolimus could offset the progression of vascular malformations and significantly improve quality of life of patients through inhibition of the Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian Target of Rapamycin (mTOR) pathway. Read More

View Article
October 2018
5 Reads
3.360 Impact Factor

One-year follow-up of B vitamin and Iron status in patients with phenylketonuria provided tetrahydrobiopterin (BH4).

Orphanet J Rare Dis 2018 Oct 30;13(1):192. Epub 2018 Oct 30.

Department of Human Genetics, Metabolic Nutrition Program, Emory University School of Medicine, Atlanta, GA, USA.

Background: People with Phenylketonuria (PKU) who respond to tetrahydrobiopterin (BH4) often decrease dependence on medical food (MF) following increased phenylalanine (phe) tolerance. Responders to BH4 may experience a reduction in certain nutrients if not compensated through intact foods or supplements. This study investigated B6, B12, folate, and iron status based on blood levels and dietary intake in patients with PKU responsive to BH4 over 1 year. Read More

View Article
October 2018
5 Reads

White matter microstructural damage in early treated phenylketonuric patients.

Orphanet J Rare Dis 2018 Oct 26;13(1):188. Epub 2018 Oct 26.

Neuropediatric Department, PKU Follow Up Unit, Hospital Sant Joan de Déu (HSJD), Institut de Recerca Sant Joan de Deu (IRSJD), Passeig Sant Joan de Deu 2, Postal code, 08950, Barcelona, Spain.

Background: Despite dietary intervention, individuals with early treated phenylketonuria (ETPKU) could present neurocognitive deficits and white matter (WM) abnormalities. The aim of the present study was to evaluate the microstructural integrity of WM pathways across the whole brain in a cohort of paediatric ETPKU patients compared with healthy controls (HCs), by collecting DTI-MRI (diffusion tensor magnetic resonance imaging) data and diffusion values (mean diffusivity (MD), radial diffusivity (RD) and fractional anisotropy (FA)).

Methods: DTI-MRI data and diffusion values (MD, RD, FA) from WM tracts across the whole brain were analized using Tract Based Spatial Statistics (TBSS), in 15 paediatrics TPKU patients (median age: 12 years) and compared with 11 HCs. Read More

View Article
October 2018
8 Reads

Follow-up analysis of voice quality in patients with late-onset Pompe disease.

Orphanet J Rare Dis 2018 Oct 26;13(1):189. Epub 2018 Oct 26.

Department of Paediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute in Warsaw, Warsaw, Poland.

Background: Late-onset Pompe disease (LOPD) is a metabolic myopathy disorder characterized by progressive muscle damage and among others dysfunction of the voice apparatus, which affects speech and - above all - voice quality. Symptoms include dysphonia, instability, glottic insufficiency, and tense voice. The aim of this study was to evaluate and compare voice quality disorder in a group of 15 LOPD patients who were first examined in 2014 and then re-examined in 2017. Read More

View Article
October 2018
5 Reads

Oral health-related quality of life in children and adolescents with osteogenesis imperfecta: cross-sectional study.

Orphanet J Rare Dis 2018 Oct 25;13(1):187. Epub 2018 Oct 25.

Division of Oral Health and Society, Faculty of Dentistry, McGill University, 2001 McGill College, Suite 500, Montreal, Quebec, H3A 1G1, Canada.

Background: Osteogenesis imperfecta (OI) affects dental and craniofacial development and may therefore impair Oral Health-Related Quality of Life (OHRQoL). However, little is known about OHRQoL in children and adolescents with OI. The aim of this study was to explore the influence of OI severity on oral health-related quality of life in children and adolescents. Read More

View Article
October 2018
2 Reads

Using Bayesian methodology to explore the profile of mental health and well-being in 646 mothers of children with 13 rare genetic syndromes in relation to mothers of children with autism.

Orphanet J Rare Dis 2018 Oct 25;13(1):185. Epub 2018 Oct 25.

Cerebra Centre for Neurodevelopmental Disorders, School of Psychology, University of Birmingham, Birmingham, B15 2TT, UK.

Background: It is well documented that mothers of children with intellectual disabilities or autism experience elevated stress, with mental health compromised. However, comparatively little is known about mothers of children with rare genetic syndromes. This study describes mental health and well-being in mothers of children with 13 rare genetic syndromes and contrasts the results with mothers of children with autism. Read More

View Article
October 2018
7 Reads

Recent advances in methodology for clinical trials in small populations: the InSPiRe project.

Orphanet J Rare Dis 2018 Oct 25;13(1):186. Epub 2018 Oct 25.

Warwick Medical School, University of Warwick, Coventry, UK.

Where there are a limited number of patients, such as in a rare disease, clinical trials in these small populations present several challenges, including statistical issues. This led to an EU FP7 call for proposals in 2013. One of the three projects funded was the Innovative Methodology for Small Populations Research (InSPiRe) project. Read More

View Article
October 2018
5 Reads

Investigating the landscape of US orphan product approvals.

Orphanet J Rare Dis 2018 Oct 22;13(1):183. Epub 2018 Oct 22.

Office of Planning, Office of the Commissioner, US Food and Drug Administration, Silver Spring, USA.

Background: The Orphan Drug Act was enacted in 1983 to encourage the development of drugs for rare diseases. Previous research has attempted to examine the impact of the Act by assessing either the number of orphan designations that have been granted or the number of new orphan drugs approved for marketing. This study provides a more in-depth understanding of the effect of the Orphan Drug Act by investigating all types of drug approvals with an orphan designation, along with multiple characteristics of the drugs, over the entire 35 years of the Act. Read More

View Article
October 2018

Comorbid connective tissue diseases and autoantibodies in lymphangioleiomyomatosis: a retrospective cohort study.

Orphanet J Rare Dis 2018 Oct 20;13(1):182. Epub 2018 Oct 20.

Clinical Research Centre, National Hospital Organization Kinki-Chuo Chest Medical Centre, 1180 Nagasone-cho, Kita-ku, Sakai City, Osaka, 591-8555, Japan.

Background: Lymphangioleiomyomatosis (LAM) and connective tissue diseases (CTDs) occur more frequently among women than men. We investigated the frequency of comorbid CTD and positive serum autoantibody findings in patients with LAM.

Methods: A total of 152 patients with LAM were prospectively and consecutively registered in the National Hospital Organization Kinki-Chuo Chest Medical Centre cohort. Read More

View Article
October 2018
1 Read

Estrogen is involved in hemangioma regression associated with mast cells.

Orphanet J Rare Dis 2018 Oct 19;13(1):181. Epub 2018 Oct 19.

Center for the Investigation of Congenital Aberrancies of Vascular Development, Little Rock, AR, USA.

Background: Estrogen plays a role in infantile hemangioma (IH) development, but the underlying mechanism remains unclear. This study aimed to assess estrogen and estrogen receptor (ER) localization and expression levels in IH. In addition, the unexpected relationship between mast cells (MCs) and estrogen in human IH was discussed. Read More

View Article
October 2018
4 Reads

Treatment patterns and healthcare resource utilization among patients with hereditary angioedema in the United States.

Orphanet J Rare Dis 2018 Oct 12;13(1):180. Epub 2018 Oct 12.

CSL Behring, King of Prussia, PA, USA.

Background: Real-world data on usage and associated outcomes with hereditary angioedema (HAE)-specific medications introduced to the United States (US) market since 2009 are very limited. The purpose of this retrospective study was to evaluate real-world treatment patterns of HAE-specific medications in the US and to assess their impact on healthcare resource utilization (HCRU). This analysis used IMS PharMetrics PlusTM database records (2006-2014) of patients with HAE, ≥1 insurance claim for an HAE-specific medication, and continuous insurance enrollment for ≥3 months following the first HAE prescription claim. Read More

View Article
October 2018
2 Reads
3.360 Impact Factor

Economic impact of screening for X-linked Adrenoleukodystrophy within a newborn blood spot screening programme.

Orphanet J Rare Dis 2018 Oct 11;13(1):179. Epub 2018 Oct 11.

School of Health and Related Research, The University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK.

Background: A decision tree model was built to estimate the economic impact of introducing screening for X-linked adrenoleukodystrophy (X-ALD) into an existing tandem mass spectrometry based newborn screening programme. The model was based upon the UK National Health Service (NHS) Newborn Blood Spot Screening Programme and a public service perspective was used with a lifetime horizon. The model structure and parameterisation were based upon literature reviews and expert clinical judgment. Read More

View Article
October 2018
4 Reads

Description of the molecular and phenotypic spectrum of Wiedemann-Steiner syndrome in Chinese patients.

Orphanet J Rare Dis 2018 Oct 11;13(1):178. Epub 2018 Oct 11.

Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.

Background: Wiedemann-Steiner syndrome (WDSTS) is a rare genetic disorder characterized by facial gestalt, neurodevelopmental delay, skeletal anomalies and growth retardation, which is caused by variation of KMT2A gene. To date, only 2 Chinese WDSTS patients have been reported. Here, we report the phenotypes and KMT2A gene variations in 14 unrelated Chinese WDSTS patients and investigate the phenotypic differences between the Chinese and French cohorts. Read More

View Article
October 2018
6 Reads
3.360 Impact Factor

The Italian neuromuscular registry: a coordinated platform where patient organizations and clinicians collaborate for data collection and multiple usage.

Orphanet J Rare Dis 2018 Oct 4;13(1):176. Epub 2018 Oct 4.

UOC Malattie neurodegenerative e neurometaboliche rare, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

Background: The worldwide landscape of patient registries in the neuromuscular disease (NMD) field has significantly changed in the last 10 years, with the international TREAT-NMD network acting as strong driver. At the same time, the European Medicines Agency and the large federations of rare disease patient organizations (POs), such as EURORDIS, contributed to a great cultural change, by promoting a paradigm shift from product-registries to patient-centred registries. In Italy, several NMD POs and Fondazione Telethon undertook the development of a TREAT-NMD linked patient registry in 2009, with the referring clinical network providing input and support to this initiative through the years. Read More

View Article
October 2018
3 Reads

Autosomal-dominant transthyretin (TTR)-related amyloidosis is not a frequent CMT2 neuropathy "in disguise".

Orphanet J Rare Dis 2018 Oct 4;13(1):177. Epub 2018 Oct 4.

Dept. of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genoa, Viale Benedetto XV, Largo P. Daneo 3, 16132, Genoa, Italy.

Transthyretin (TTR)-related familial amyloid polyneuropathy (TTR-FAP) is a life-threatening autosomal dominant, systemic disease. First symptoms usually occur from the second to over sixth decade of life with a length-dependent axonal neuropathy with prominent involvement of the small fibers and multi-organ systemic failure.Early diagnosis is pivotal for effective therapeutic options, but it is hampered by the heterogeneity of the clinical spectrum which can lead to misdiagnosis with other neurological condition/disorder such as axonal sensory-motor neuropathy (CMT2) as described in literature. Read More

View Article
October 2018
2 Reads