Articles

Immune cell phenotype and functional defects in Netherton syndrome

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 unders...

Authors: Elina Eränkö, Mette Ilander, Mirja Tuomiranta, Antti Mäkitie, Tea Lassila, Anna Kreutzman, Paula Klemetti, Satu Mustjoki, Katariina Hannula-Jouppi and Annamari Ranki

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

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.

Authors: Minela Haskovic, Britt Derks, Liesbeth van der Ploeg, Jorn Trommelen, Jean Nyakayiru, Luc J. C. van Loon, Sabrina Mackinnon, Wyatt W. Yue, Roy W. A. Peake, Li Zha, Didem Demirbas, Wanshu Qi, Xiaoping Huang, Gerard T. Berry, Jelle Achten, Jörgen Bierau…

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

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 rapidl...

Authors: Rachel Thompson, Angela Abicht, David Beeson, Andrew G. Engel, Bruno Eymard, Emmanuel Maxime and Hanns Lochmüller

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

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 i...

Authors: Bruce Cohen, Cristy Balcells, Brian Hotchkiss, Kavita Aggarwal and Amel Karaa

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

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 ner...

Authors: Kim Maincent, Bénédicte Héron, Thierry Billette de Villemeur and Michèle Mayer

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

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...

Authors: Takeya Adachi, Noriaki Imanishi, Yasushi Ogawa, Yoshihiko Furusawa, Yoshihiko Izumida, Yoko Izumi and Makoto Suematsu

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

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 gynecologi...

Authors: Elina Holopainen, Svetlana Vakkilainen and Outi Mäkitie

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

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 su...

Authors: 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 and Ferran Torres

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

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 combinat...

Authors: Francesca Marini, Francesca Giusti and Maria Luisa Brandi

Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis

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 lymphangiol...

Authors: Hee-Young Yoon, Jung Jin Hwang, Dong Soon Kim and Jin Woo Song

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

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 le...

Authors: José A. E. Custers, Paul de Laat, Saskia Koene, Jan Smeitink, Mirian C. H. Janssen and Christianne Verhaak

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

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, registri...

Authors: Monique Garcia, Jenny Downs, Alyce Russell and Wei Wang

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

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 o...

Authors: Irina Odnoletkova, Gerhard Kindle, Isabella Quinti, Bodo Grimbacher, Viviane Knerr, Benjamin Gathmann, Stephan Ehl, Nizar Mahlaoui, Philippe Van Wilder, Kris Bogaerts and Esther de Vries

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

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 deve...

Authors: 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…

Federating patients identities: the case of rare diseases

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. Transfor...

Authors: Meriem Maaroufi, Paul Landais, Claude Messiaen, Marie-Christine Jaulent and Rémy Choquet

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

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 w...

Authors: Abiola O. Oladapo, Mei Lu, Shaun Walsh, Jamie O’Hara and Teresa L. Kauf

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

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 childhoo...

Authors: Antonia Reimer, Leena Bruckner-Tuderman and Hagen Ott

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

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 adva...

Authors: Petra Kaufmann, Anne R. Pariser and Christopher Austin

Recommendations for the design of small population clinical trials

Orphan drug development faces numerous challenges, including low disease prevalence, patient population heterogeneity, and strong presence of paediatric patient populations. Consequently, clinical trials for o...

Authors: Simon Day, Anneliene Hechtelt Jonker, Lilian Pek Lian Lau, Ralf-Dieter Hilgers, Ilan Irony, Kristina Larsson, Kit CB Roes and Nigel Stallard

The European challenges of funding orphan medicinal products

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

Authors: 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 and Mária Judit Molnár

Nerve ultrasound characterizes AMN polyneuropathy as inhomogeneous and focal hypertrophic

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 adrenomyeloneurop...

Authors: Tim W. Rattay, Jennifer Just, Benjamin Röben, Holger Hengel, Rebecca Schüle, Matthis Synofzik, Anne S. Söhn, Natalie Winter, Nele Dammeier, Ludger Schöls and Alexander Grimm

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

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 aft...

Authors: Michael Ablinger, Thomas K. Felder, Monika Wimmer, Roland Zauner, Peter Hofbauer, Thomas Lettner, Martin Wolkersdorfer, Florian B. Lagler, Anja Diem, Johann W. Bauer and Verena Wally

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

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 r...

Authors: Kristen D Brantley, Teresa D Douglas and Rani H Singh

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

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...

Authors: Jennifer Hammer, Emmanuel Seront, Steven Duez, Sophie Dupont, An Van Damme, Sandra Schmitz, Claire Hoyoux, Caroline Chopinet, Philippe Clapuyt, Frank Hammer, Miikka Vikkula and Laurence M. Boon

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

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 rep...

Authors: Emmanuel Gonzales, Lorenza Matarazzo, Stéphanie Franchi-Abella, Alain Dabadie, Joseph Cohen, Dalila Habes, Sophie Hillaire, Catherine Guettier, Anne-Marie Taburet, Anne Myara and Emmanuel Jacquemin

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

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 qua...

Authors: Krzysztof Szklanny and Anna Tylki-Szymańska

White matter microstructural damage in early treated phenylketonuric patients

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 ...

Authors: María Julieta González, Mónica Rebollo Polo, Pablo Ripollés, Rosa Gassió, Aída Ormazabal, Cristina Sierra, Roser Colomé Roura, Rafael Artuch and Jaume Campistol

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

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...

Authors: Mohammadamin Najirad, Mang Shin Ma, Frank Rauch, Vernon Reid Sutton, Brendan Lee, Jean-Marc Retrouvey and Shahrokh Esfandiari

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

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 prop...

Authors: Tim Friede, Martin Posch, Sarah Zohar, Corinne Alberti, Norbert Benda, Emmanuelle Comets, Simon Day, Alex Dmitrienko, Alexandra Graf, Burak Kürsad Günhan, Siew Wan Hee, Frederike Lentz, Jason Madan, Frank Miller, Thomas Ondra, Michael Pearce…

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

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 child...

Authors: Dawn Adams, Richard P Hastings, Clair Alston-Knox, Rina Cianfaglione, Kate Eden, David Felce, Gemma Griffith, Jo Moss, Chris Stinton and Chris Oliver

Investigating the landscape of US orphan product approvals

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 design...

Authors: Kathleen L. Miller and Michael Lanthier

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

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 patien...

Authors: Shinji Futami, Toru Arai, Masaki Hirose, Chikatoshi Sugimoto, Naoya Ikegami, Masanori Akira, Takahiko Kasai, Masanori Kitaichi, Seiji Hayashi and Yoshikazu Inoue

Estrogen is involved in hemangioma regression associated with mast cells

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 i...

Authors: Fang Hou, Yuemeng Dai, Chun-Yang Fan, James Y. Suen and Gresham T. Richter

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

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...

Authors: Marc A Riedl, Aleena Banerji, Michael E Manning, Earl Burrell, Namita Joshi, Dipen Patel, Thomas Machnig, Ming-Hui Tai and Douglas J Watson

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

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. T...

Authors: Alice Bessey, James B Chilcott, Joanna Leaviss and Anthea Sutton

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

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 d...

Authors: Niu Li, Yirou Wang, Yu Yang, Pengpeng Wang, Hui Huang, Shiyi Xiong, Luming Sun, Min Cheng, Cui Song, Xinran Cheng, Yu Ding, Guoying Chang, Yao Chen, Yufei Xu, Tingting Yu, Ru-en Yao…

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

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 ...

Authors: Marina Grandis, Alessandro Geroldi, Rossella Gulli, Fiore Manganelli, Fabio Gotta, Merit Lamp, Paola Origone, Lucia Trevisan, Chiara Gemelli, Sabrina Fabbri, Angelo Schenone, Stefano Tozza, Lucio Santoro, Emilia Bellone and Paola Mandich

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

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 s...

Authors: Anna Ambrosini, Daniela Calabrese, Francesco Maria Avato, Felice Catania, Guido Cavaletti, Maria Carmela Pera, Antonio Toscano, Giuseppe Vita, Lucia Monaco and Davide Pareyson

Adult Niemann-Pick disease type C in France: clinical phenotypes and long-term miglustat treatment effect

Niemann-Pick disease type C (NP-C) is a neurodegenerative lysosomal lipid storage disease caused by autosomal recessive mutations in the NPC1 or NPC2 genes. The clinical presentation and evolution of NP-C and the...

Authors: Yann Nadjar, Ana Lucia Hütter-Moncada, Philippe Latour, Xavier Ayrignac, Elsa Kaphan, Christine Tranchant, Pascal Cintas, Adrian Degardin, Cyril Goizet, Chloe Laurencin, Lionel Martzolff, Caroline Tilikete, Mathieu Anheim, Bertrand Audoin, Vincent Deramecourt, Thierry Dubard De Gaillarbois…

Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing

Urea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in t...

Authors: Sunita Bijarnia-Mahay, Johannes Häberle, Anil B. Jalan, Ratna Dua Puri, Sudha Kohli, Ketki Kudalkar, Véronique Rüfenacht, Deepti Gupta, Deepshikha Maurya, Jyotsna Verma, Yosuke Shigematsu, Seiji Yamaguchi, Renu Saxena and Ishwar C. Verma

Diagnostic and therapeutic recommendations for the treatment of hyperphenylalaninemia in patients 0–4 years of age

Treatment of phenylketonuria (PKU) with sapropterin dihydrochloride in responsive patients from an early age can have many advantages for the patient over dietary restriction alone. Accordingly, approval of sa...

Authors: Ania C. Muntau, Marcel du Moulin and Francois Feillet

Cost-effectiveness analysis of lumacaftor and ivacaftor combination for the treatment of patients with cystic fibrosis in the United States

Lumacaftor/ivacaftor was approved by the Food and Drug Administration (FDA) as a combination treatment for Cystic Fibrosis (CF) patients who are homozygous for the F508del mutation. The objective of this study...

Authors: Dolly Sharma, Shan Xing, Yu-Ting Hung, Rachel N. Caskey, Maria L. Dowell and Daniel R. Touchette

Neutralizing anti-drug antibodies in Fabry disease have no obvious clinical impact?

Fabry disease (FD) is a rare X-linked disorder caused by a deficiency of lysosomal α-galactosidase A activity. Treatment with recombinant enzyme replacement therapy is available since 2001 and the effects of a...

Authors: Malte Lenders, Boris Schmitz, Stefan-Martin Brand and Eva Brand

9th European Conference on Rare Diseases & Orphan Products (ECRD Vienna 2018)

Authors:

Broad phenotypic spectrum and genotype-phenotype correlations in GMPPB-related dystroglycanopathies: an Italian cross-sectional study

Dystroglycanopathy (α-DG) is a relatively common, clinically and genetically heterogeneous category of congenital forms of muscular dystrophy (CMD) and limb-girdle muscular dystrophy (LGMD) associated with hyp...

Authors: Guja Astrea, Alessandro Romano, Corrado Angelini, Carlo Giuseppe Antozzi, Rita Barresi, Roberta Battini, Carla Battisti, Enrico Bertini, Claudio Bruno, Denise Cassandrini, Marina Fanin, Fabiana Fattori, Chiara Fiorillo, Renzo Guerrini, Lorenzo Maggi, Eugenio Mercuri…

High hepatic macrophage activation and low liver function in stable Wilson patients - a Danish cross-sectional study

Hepatic macrophage (Kupffer cell) hyperplasia is often described in Wilson’s disease (WD). In many liver diseases, Kupffer cell activation is related to disease severity, liver function, and fibrosis but the i...

Authors: Jessica Björklund, Tea Lund Laursen, Thomas Damgaard Sandahl, Holger Jon Møller, Hendrik Vilstrup, Peter Ott and Henning Grønbæk

Efficacy of sirolimus for the prevention of recurrent pneumothorax in patients with lymphangioleiomyomatosis: a case series

Pneumothorax is one of the most common symptoms in patients with lymphangioleiomyomatosis (LAM). However, current management strategies for patients with LAM who present with recurrent pneumothorax remain inad...

Authors: Li Zhou, Ruoyun Ouyang, Hong Luo, Siying Ren, Ping Chen, Yating Peng, Ting Liu and Guiqian Liu

Molecular and cellular characterizations of human cherubism: disease aggressiveness depends on osteoclast differentiation

Cherubism is a rare autosomal dominant disorder of the jaws caused by mutation of the SH3BP2 gene. The bone is replaced by a fibrous granuloma containing multinucleated giant cells. Cells of the cherubism granulo...

Authors: Natacha Kadlub, Quentin Sessiecq, Marion Mandavit, Aurore Coulomb L’Hermine, Cecile Badoual, Louise Galmiche, Ariane Berdal, Vianney Descroix, Arnaud Picard and Amélie E. Coudert

From motor performance to participation: a quantitative descriptive study in adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) is a recessive neurological disorder with cerebellar, pyramidal and neuropathic features. Natural history data are urgently needed to increase...

Authors: Cynthia Gagnon, Bernard Brais, Isabelle Lessard, Caroline Lavoie, Isabelle Côté and Jean Mathieu

Fertility in classical galactosaemia, a study of N-glycan, hormonal and inflammatory gene interactions

Classical Galactosaemia (CG) (OMIM #230400) is a rare inborn error of galactose metabolism caused by deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). Long-term complications persist i...

Authors: Hugh-Owen Colhoun, Estela M. Rubio Gozalbo, Annet M. Bosch, Ina Knerr, Charlotte Dawson, Jennifer Brady, Marie Galligan, Karolina Stepien, Roisin O’Flaherty, C. Catherine Moss, P. Peter Barker, Maria Fitzgibbon, Peter P. Doran and Eileen P. Treacy