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Orphanet Journal of Rare Diseases

Elina Holopainen, Svetlana Vakkilainen, Outi Mäkitie
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. METHODS: We carried out gynecologic evaluation, pelvic ultrasound and laboratory assessment in 19 women with genetically confirmed CHH...
November 16, 2018: Orphanet Journal of Rare Diseases
Caridad Pontes, Juan Manuel Fontanet, Roser Vives, Aranzazu Sancho, Mònica Gómez-Valent, José Ríos, Rosa Morros, Jorge Martinalbo, Martin Posch, Armin Koch, Kit Roes, Katrien Oude Rengerink, Josep Torrent-Farnell, Ferran Torres
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...
November 15, 2018: Orphanet Journal of Rare Diseases
Francesca Marini, Francesca Giusti, Maria Luisa Brandi
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...
November 14, 2018: Orphanet Journal of Rare Diseases
Hee-Young Yoon, Jung Jin Hwang, Dong Soon Kim, Jin Woo Song
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. Clinical data of 39 patients with lymphangioleiomyomatosis (mean age, 34.8 years; median treatment period, 29...
November 14, 2018: Orphanet Journal of Rare Diseases
José A E Custers, Paul de Laat, Saskia Koene, Jan Smeitink, Mirian C H Janssen, Christianne Verhaak
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. This could easily result in fear of disease progression. This study investigated the presence of this fear and its correlates with genetic characteristics and clinical disease severity in m...
November 13, 2018: Orphanet Journal of Rare Diseases
Irina Odnoletkova, Gerhard Kindle, Isabella Quinti, Bodo Grimbacher, Viviane Knerr, Benjamin Gathmann, Stephan Ehl, Nizar Mahlaoui, Philippe Van Wilder, Kris Bogaerts, Esther de Vries
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. The registered deaths and comorbidities were used to calculate the annual average age-standardized rates of Years of Life Lost to premature death (YLL), Years Lost to Disability (YLD) and Disability Adjusted Life Years (DALY=YLL + YLD)...
November 12, 2018: Orphanet Journal of Rare Diseases
Marian Mitroiu, Katrien Oude Rengerink, Caridad Pontes, Aranzazu Sancho, Roser Vives, Stella Pesiou, Juan Manuel Fontanet, Ferran Torres, Stavros Nikolakopoulos, Konstantinos Pateras, Gerd Rosenkranz, Martin Posch, Susanne Urach, Robin Ristl, Armin Koch, Spineli Loukia, Johanna H van der Lee, Kit C B Roes
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...
November 12, 2018: Orphanet Journal of Rare Diseases
Monique Garcia, Jenny Downs, Alyce Russell, Wei Wang
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)...
November 12, 2018: Orphanet Journal of Rare Diseases
Meriem Maaroufi, Paul Landais, Claude Messiaen, Marie-Christine Jaulent, Rémy Choquet
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. We propose a method enabling patient identity federation and rare disease data de-identification while preserving the pertinence of the provided data...
November 12, 2018: Orphanet Journal of Rare Diseases
Abiola O Oladapo, Mei Lu, Shaun Walsh, Jamie O'Hara, Teresa L Kauf
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...
November 9, 2018: Orphanet Journal of Rare Diseases
Antonia Reimer, Leena Bruckner-Tuderman, Hagen Ott
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. With an estimate of up to 2000 affected individuals in Germany, many of these children, but only two specialist centres, the question arose where and how health care for this rare disease is provided...
November 8, 2018: Orphanet Journal of Rare Diseases
Simon Day, Anneliene Hechtelt Jonker, Lilian Pek Lian Lau, Ralf-Dieter Hilgers, Ilan Irony, Kristina Larsson, Kit Cb Roes, Nigel Stallard
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...
November 6, 2018: Orphanet Journal of Rare Diseases
Petra Kaufmann, Anne R Pariser, Christopher Austin
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. This challenges us as a society to accelerate progress so that no disease and no patient is, ultimately, left behind in getting access to safe and effective therapeutics...
November 6, 2018: Orphanet Journal of Rare Diseases
Márta Szegedi, Tamás Zelei, Francis Arickx, Anna Bucsics, Emanuelle Cohn-Zanchetta, Jurij Fürst, Maria Kamusheva, Pawel Kawalec, Guenka Petrova, Juraj Slaby, Ewa Stawowczyk, Milan Vocelka, Ingrid Zechmeister-Koss, Zoltán Kaló, Mária Judit Molnár
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...
November 6, 2018: Orphanet Journal of Rare Diseases
Tim W Rattay, Jennifer Just, Benjamin Röben, Holger Hengel, Rebecca Schüle, Matthis Synofzik, Anne S Söhn, Natalie Winter, Nele Dammeier, Ludger Schöls, Alexander Grimm
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. Ultrasound results were correlated with clinical findings and nerve conduction studies...
November 3, 2018: Orphanet Journal of Rare Diseases
Michael Ablinger, Thomas K Felder, Monika Wimmer, Roland Zauner, Peter Hofbauer, Thomas Lettner, Martin Wolkersdorfer, Florian B Lagler, Anja Diem, Johann W Bauer, Verena Wally
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. Ex vivo experiments using a Franz diffusion cell confirmed the uptake and bio-transformation of diacerein to rhein in a porcine skin model...
November 1, 2018: Orphanet Journal of Rare Diseases
Kristen D Brantley, Teresa D Douglas, Rani H Singh
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. METHODS: Fifty-eight patients with PKU, ages 4-50 years were recruited and initiated on BH4 therapy...
October 30, 2018: Orphanet Journal of Rare Diseases
Emmanuel Gonzales, Lorenza Matarazzo, Stéphanie Franchi-Abella, Alain Dabadie, Joseph Cohen, Dalila Habes, Sophie Hillaire, Catherine Guettier, Anne-Marie Taburet, Anne Myara, Emmanuel Jacquemin
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. METHODS: Fifteen patients with either 3β-hydroxy-Δ5 -C27 -steroid oxidoreductase (3β-HSD) (n = 13) or Δ4 -3-oxosteroid 5β-reductase (Δ4 -3-oxo-R) (n = 2) deficiency confirmed by mass spectrometry and gene sequencing received oral CA and were followed prospectively...
October 29, 2018: Orphanet Journal of Rare Diseases
Jennifer Hammer, Emmanuel Seront, Steven Duez, Sophie Dupont, An Van Damme, Sandra Schmitz, Claire Hoyoux, Caroline Chopinet, Philippe Clapuyt, Frank Hammer, Miikka Vikkula, Laurence M Boon
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...
October 29, 2018: Orphanet Journal of Rare Diseases
María Julieta González, Mónica Rebollo Polo, Pablo Ripollés, Rosa Gassió, Aída Ormazabal, Cristina Sierra, Roser Colomé Roura, Rafael Artuch, Jaume Campistol
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))...
October 26, 2018: Orphanet Journal of Rare Diseases
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