Articles

Lessons learned from IDeAl — 33 recommendations from the IDeAl-net about design and analysis of small population clinical trials

IDeAl (Integrated designs and analysis of small population clinical trials) is an EU funded project developing new statistical design and analysis methodologies for clinical trials in small population groups. ...

Authors: Ralf-Dieter Hilgers, Malgorzata Bogdan, Carl-Fredrik Burman, Holger Dette, Mats Karlsson, Franz König, Christoph Male, France Mentré, Geert Molenberghs and Stephen Senn

Naxos disease: from the origin to today

Naxos disease, first described by Dr. Nikos Protonotarios and colleagues on the island of Naxos, Greece, is a special form of arrhythmogenic right ventricular dysplasia (ARVD). It is an inherited condition wit...

Authors: Guo-Liang Li, Ardan M. Saguner and Guy H. Fontaine

Maternal drug use and the risk of anorectal malformations: systematic review and meta-analysis

Origin of anorectal malformations (ARM) are considered multifactorial. Several genetic and non-genetic risk factors are discussed in literature. Maternal periconceptional medical drug use as possible risk fact...

Authors: Nadine Zwink and Ekkehart Jenetzky

Epidemiology of Bradykinin-mediated angioedema: a systematic investigation of epidemiological studies

Bradykinin-mediated angioedema (Bk-AE) can be life-threatening and requires specific targeted therapies. Knowledge of its epidemiology may help optimize its management.

Authors: Emel Aygören-Pürsün, Markus Magerl, Andreas Maetzel and Marcus Maurer

Individualized approach to the surgical management of fibrous dysplasia of the proximal femur

Fibrous dysplasia of the proximal femur presents with heterogeneous clinical manifestations dictating different surgical approaches. However, to date there are no clear recommendations to guide the choice of s...

Authors: Bas C. J. Majoor, Andreas Leithner, Michiel A. J. van de Sande, Natasha M. Appelman-Dijkstra, Neveen A. T. Hamdy and P. D. Sander Dijkstra

GNE myopathy: from clinics and genetics to pathology and research strategies

GNE myopathy is an ultra-rare autosomal recessive disease, which starts as a distal muscle weakness and ultimately leads to a wheelchair bound state. Molecular research and animal modelling significantly moved...

Authors: Oksana Pogoryelova, José Andrés González Coraspe, Nikoletta Nikolenko, Hanns Lochmüller and Andreas Roos

Liver transplantation for very severe hepatopulmonary syndrome due to vitamin A-induced chronic liver disease in a patient with Shwachman-Diamond syndrome

Vitamin A intoxication is a rare cause of liver disease, but the risk increases in patients with underlying liver dysfunction. We present a patient with Shwachman-Diamond Syndrome who developed liver fibrosis,...

Authors: Giorgia Bucciol, David Cassiman, Tania Roskams, Marleen Renard, Ilse Hoffman, Peter Witters, Rik Schrijvers, Heidi Schaballie, Barbara Bosch, Maria Caterina Putti, Olivier Gheysens, Noel Knops, Marc Gewillig, Djalila Mekahli, Jacques Pirenne and Isabelle Meyts

Detection rate of causal variants in severe childhood epilepsy is highest in patients with seizure onset within the first four weeks of life

Epilepsy is a heterogeneous disease with a broad phenotypic spectrum and diverse genotypes. A significant proportion of epilepsies has a genetic aetiology.

Authors: David Staněk, Petra Laššuthová, Katalin Štěrbová, Markéta Vlčková, Jana Neupauerová, Marcela Krůtová and Pavel Seeman

Revealed preferences towards the appraisal of orphan drugs in Poland - multi criteria decision analysis

A Multi Criteria Decision Analysis (MCDA) technique was adopted to reveal the preferences of the Appraisal Body of the Polish HTA agency towards orphan drugs (OMPs).

Authors: Katarzyna Kolasa, Krzysztof Miroslaw Zwolinski, Vladimir Zah, Zoltán Kaló and Tadeusz Lewandowski

European principles of inhibitor management in patients with haemophilia

In spite of recent major advances in the understanding and treatment of inhibitor development in patients with haemophilia, multidisciplinary management of many of these patients remains suboptimal and highly ...

Authors: P. L. F. Giangrande, C. Hermans, B. O’Mahony, P. de Kleijn, M. Bedford, A. Batorova, J. Blatný and K. Jansone

Migalastat improves diarrhea in patients with Fabry disease: clinical-biomarker correlations from the phase 3 FACETS trial

Fabry disease is frequently characterized by gastrointestinal symptoms, including diarrhea. Migalastat is an orally-administered small molecule approved to treat the symptoms of Fabry disease in patients with ...

Authors: Raphael Schiffmann, Daniel G. Bichet, Ana Jovanovic, Derralynn A. Hughes, Roberto Giugliani, Ulla Feldt-Rasmussen, Suma P. Shankar, Laura Barisoni, Robert B. Colvin, J. Charles Jennette, Fred Holdbrook, Andrew Mulberg, Jeffrey P. Castelli, Nina Skuban, Jay A. Barth and Kathleen Nicholls

Adenosine deaminase deficiency: a review

Adenosine deaminase (ADA) deficiency leads to an accumulation of toxic purine degradation by-products, most potently affecting lymphocytes, leading to adenosine deaminase-deficient severe combined immunodefici...

Authors: Aisling M. Flinn and Andrew R. Gennery

Patient reported outcome measures in rare diseases: a narrative review

Rare diseases can lead to a significant reduction in quality of life for patients and their families. Ensuring the patients voice is central to clinical decision making is key to delivering, evaluating and und...

Authors: Anita Slade, Fatima Isa, Derek Kyte, Tanya Pankhurst, Larissa Kerecuk, James Ferguson, Graham Lipkin and Melanie Calvert

Serial MRIs provide novel insight into natural history of optic pathway gliomas in patients with neurofibromatosis 1

Optic pathway gliomas (OPGs) are present in 20% of children with neurofibromatosis 1 (NF1) but are less frequently observed in adults. Our goal was to determine the natural history of OPGs in children and adul...

Authors: Laura Sellmer, Said Farschtschi, Marco Marangoni, Manraj K. S. Heran, Patricia Birch, Ralph Wenzel, Victor-Felix Mautner and Jan M. Friedman

Gastro-oesophageal reflux - an important causative factor of severe tooth wear in Prader-Willi syndrome?

Prader-Willi syndrome (PWS) is the most common genetic human obesity syndrome and is characterized by hypotonia, endocrine disturbances, hyperphagia, obesity and mild mental retardation. Oral abnormalities, su...

Authors: Ronnaug Saeves, Finn Strøm, Leiv Sandvik and Hilde Nordgarden

Less invasive treatment of sleep-disordered breathing in children with syndromic craniosynostosis

Infants and children with syndromic craniosynostosis (SCS), such as Apert-, Crouzon- or Pfeiffer syndrome, are prone to sleep disordered breathing (SDB) including obstructive sleep apnea and upper airway resis...

Authors: Silvia Müller-Hagedorn, Cornelia Wiechers, Jörg Arand, Wolfgang Buchenau, Margit Bacher, Michael Krimmel, Siegmar Reinert and Christian F. Poets

Decreased quality of life and societal impact of cryopyrin-associated periodic syndrome treated with canakinumab: a questionnaire based cohort study

Cryopyrin-associated periodic syndrome (CAPS) is a rare disease. Knowledge on the quality of life (QoL) and the disease’s societal impact is limited. Canakinumab is used in increasing frequency for the treatme...

Authors: Catharina M. Mulders-Manders, Tim A. Kanters, Paul L. A. van Daele, Esther Hoppenreijs, G. Elizabeth Legger, Jan A. M. van Laar, Anna Simon and Leona Hakkaart-van Roijen

Pulmonary hemosiderosis in children with Down syndrome: a national experience

Pulmonary hemosiderosis is a rare and complex disease in children. A previous study from the French RespiRare® network led to two important findings: 20% of the children presented with both pulmonary hemosider...

Authors: Aurelia Alimi, Jessica Taytard, Rola Abou Taam, Véronique Houdouin, Aude Forgeron, Marc Lubrano Lavadera, Pierrick Cros, Isabelle Gibertini, Jocelyne Derelle, Antoine Deschildre, Caroline Thumerelle, Ralph Epaud, Philippe Reix, Michael Fayon, Sylvie Roullaud, Françoise Troussier…

Gastrointestinal and urinary complaints in adults with hereditary spastic paraparesis

Hereditary spastic paraparesis (HSP) is a group of rare genetic disorders affecting the central nervous system. Pure HSP is limited to lower limb spasticity and urinary voiding dysfunction. Complex HSP involve...

Authors: Øivind J. Kanavin and Krister W. Fjermestad

Decreased outlet angle of the superior cerebellar artery as indicator for dolichoectasia in late onset Pompe disease

Lysosomal α-glucosidase deficiency (Pompe disease) not only leads to glycogen accumulation in skeletal muscle, but also in the cerebral arteries. Dolichoectasia of the basilar artery (BA) has been frequently r...

Authors: Ole Hensel, Ilka Schneider, Mathias Wieprecht, Torsten Kraya and Stephan Zierz

Epidemiology of Sanfilippo syndrome: results of a systematic literature review

Sanfilippo syndrome (mucopolysaccharidosis [MPS] III subtypes A, B, C, and D) is a rare autosomal recessive inherited metabolic disorder that causes progressive neurocognitive degeneration. This systematic lit...

Authors: Tamás Zelei, Kata Csetneki, Zoltán Vokó and Csaba Siffel

Epidermal necrolysis French national diagnosis and care protocol (PNDS; protocole national de diagnostic et de soins)

Epidermal necrolysis (EN) encompasses Stevens-Johnson syndrome (SJS, < 10% of the skin affected), Lyell syndrome (toxic epidermal necrolysis, TEN, with ≥30% of the skin affected) and an overlap syndrome (10 to...

Authors: Saskia Ingen-Housz-Oro, Tu-Anh Duong, Benoit Bensaid, Nathalia Bellon, Nicolas de Prost, Dévy Lu, Bénédicte Lebrun-Vignes, Julie Gueudry, Emilie Bequignon, Karim Zaghbib, Gérard Royer, Audrey Colin, Giao Do-Pham, Christine Bodemer, Nicolas Ortonne, Annick Barbaud…

Neural stem cells for disease modeling and evaluation of therapeutics for infantile (CLN1/PPT1) and late infantile (CLN2/TPP1) neuronal ceroid lipofuscinoses

Infantile and late infantile neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases affecting the central nervous system (CNS). The infantile NCL (INCL) is caused by mutations in the PPT1 gene and l...

Authors: Ni Sima, Rong Li, Wei Huang, Miao Xu, Jeanette Beers, Jizhong Zou, Steven Titus, Elizabeth A. Ottinger, Juan J. Marugan, Xing Xie and Wei Zheng

Fabry disease in the Spanish population: observational study with detection of 77 patients

Fabry disease is a multisystemic lysosomal storage disorder caused by the impairment of α-galactosidase A. The incidence of this rare disease is underestimated due to delayed diagnosis. Moreover, the managemen...

Authors: Irene Vieitez, Olga Souto-Rodriguez, Lorena Fernandez-Mosquera, Beatriz San Millan, Susana Teijeira, Julian Fernandez-Martin, Felisa Martinez-Sanchez, Luis Jose Aldamiz-Echevarria, Monica Lopez-Rodriguez, Carmen Navarro and Saida Ortolano

Safety, effectiveness, and impact on quality of life of self-administration with plasma-derived nanofiltered C1 inhibitor (Berinert®) in patients with hereditary angioedema: the SABHA study

Hereditary angioedema with C1 inhibitor deficiency is a disabling, potentially fatal condition characterized by recurrent episodes of swelling. Self-treatment is recommended, in order to reduce admissions to t...

Authors: Andrea Zanichelli, Giulia Maria Azin, Federico Cristina, Romualdo Vacchini and Teresa Caballero

GAD65 autoantibody characteristics in patients with co-occurring type 1 diabetes and epilepsy may help identify underlying epilepsy etiologies

Autoantibodies against the smaller isoform of glutamate decarboxylase (GAD65Ab) reflect autoimmune etiologies in Type 1 diabetes (T1D) and several neurological disorders, including Stiff Person Syndrome (SPS)....

Authors: Suvi Liimatainen, Jerome Honnorat, Sean J. Pittock, Andrew McKeon, Mario Manto, Jared R. Radtke and Christiane S. Hampe

Consensus clinical management guidelines for Niemann-Pick disease type C

Niemann-Pick Type C (NPC) is a progressive and life limiting autosomal recessive disorder caused by mutations in either the NPC1 or NPC2 gene. Mutations in these genes are associated with abnormal endosomal-lysos...

Authors: Tarekegn Geberhiwot, Alessandro Moro, Andrea Dardis, Uma Ramaswami, Sandra Sirrs, Mercedes Pineda Marfa, Marie T. Vanier, Mark Walterfang, Shaun Bolton, Charlotte Dawson, Bénédicte Héron, Miriam Stampfer, Jackie Imrie, Christian Hendriksz, Paul Gissen, Ellen Crushell…

Gene therapy in rare diseases: the benefits and challenges of developing a patient-centric registry for Strimvelis in ADA-SCID

Strimvelis (autologous CD34+ cells transduced to express adenosine deaminase [ADA]) is the first ex vivo stem cell gene therapy approved by the European Medicines Agency (EMA), indicated as a single treatment ...

Authors: Heide Stirnadel-Farrant, Mahesh Kudari, Nadia Garman, Jessica Imrie, Bikramjit Chopra, Stefania Giannelli, Michela Gabaldo, Ambra Corti, Stefano Zancan, Alessandro Aiuti, Maria Pia Cicalese, Rohit Batta, Jonathan Appleby, Mario Davinelli and Pauline Ng

A pilot screening of high-risk Gaucher disease children using dried blood spot methods in Shandong province of China

The study aim was to verify the feasibility of a diagnostic algorithm with the evaluation of beta glucocerebrosidase (GBA) activity on dried blood spots (DBS) in screening high-risk Gaucher disease (GD) childr...

Authors: Ke Lei, Yanxia Zhao, Lirong Sun, Hui Liang, Ronghua Luo, Xiaojing Sun, Yanling Tao, Lijun Chen, Lingling Zhang, Aimin Li, Fu Li and Hongfang Ding

KARS-related diseases: progressive leukoencephalopathy with brainstem and spinal cord calcifications as new phenotype and a review of literature

KARS encodes lysyl- transfer ribonucleic acid (tRNA) synthetase, which catalyzes the aminoacylation of tRNA-Lys in the cytoplasm and mitochondria. Eleven families/sporadic patients and 16 different mutations in K...

Authors: Anna Ardissone, Davide Tonduti, Andrea Legati, Eleonora Lamantea, Rita Barone, Imen Dorboz, Odile Boespflug-Tanguy, Gabriella Nebbia, Marco Maggioni, Barbara Garavaglia, Isabella Moroni, Laura Farina, Anna Pichiecchio, Simona Orcesi, Luisa Chiapparini and Daniele Ghezzi

Alitretinoin reduces erythema in inherited ichthyosis

Acitretin is the main retinoid used to treat severe inherited ichthyosis. Alternatives may be considered if it results ineffective or there are side-effects, or for women of childbearing age.

Authors: Giuliana Onnis, Christine Chiaverini, Geoffroy Hickman, Isabelle Dreyfus, Judith Fischer, Emmanuelle Bourrat and Juliette Mazereeuw-Hautier

Bisphosphonate therapy for spinal osteoporosis in Hajdu-Cheney syndrome – new data and literature review

Hajdu-Cheney syndrome (HCS) (#OMIM 102500) is a rare, autosomal dominant condition that presents in early childhood. It is caused by mutations in the terminal exon of NOTCH2, which encodes the transmembrane NOTCH...

Authors: James F. H. Pittaway, Christopher Harrison, Yumie Rhee, Muriel Holder-Espinasse, Alan E. Fryer, Tim Cundy, William M. Drake and Melita D. Irving

A perspective on “cure” for Rett syndrome

The reversal of the Rett syndrome disease process in the Mecp2 mouse model of Guy et al. (2007) has motivated families and researchers to work on this condition. The reversibility in adult mice suggests that t...

Authors: Angus John Clarke and Ana Paula Abdala Sheikh

Assessing the outcomes of everolimus on renal angiomyolipoma associated with tuberous sclerosis complex in China: a two years trial

Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder characterized by the development of numerous benign tumors. Renal angiomyolipoma (RAML) occur in up to 80% of TSC patients, which ...

Authors: Yi Cai, Hao Guo, Wenda Wang, Hanzhong Li, Hao Sun, Bing Shi and Yushi Zhang

Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood

Hermansky-Pudlak syndrome (HPS), a hereditary multisystem disorder with oculocutaneous albinism, may be caused by mutations in one of at least 10 separate genes. The HPS-2 subtype is distinguished by the prese...

Authors: Meike Hengst, Lutz Naehrlich, Poornima Mahavadi, Joerg Grosse-Onnebrink, Suzanne Terheggen-Lagro, Lars Høsøien Skanke, Luise A. Schuch, Frank Brasch, Andreas Guenther, Simone Reu, Julia Ley-Zaporozhan and Matthias Griese

Fatal thoracic aortic aneurysm and dissection in a large family with a novel MYLK gene mutation: delineation of the clinical phenotype

Thoracic and abdominal aortic aneurysms and dissection often develop in hypertensive elderly patients. At higher risk are smokers and those who have a family history of aortic aneurysms. In most affected famil...

Authors: Adel Shalata, Mohammad Mahroom, Dianna M. Milewicz, Gong Limin, Fadi Kassum, Khader Badarna, Nader Tarabeih, Nimmer Assy, Rona Fell, Hector Cohen, Munir Nashashibi, Alejandro Livoff, Muhammad Azab, George Habib, Dan Geiger, Omer Weissbrod…

Frequency of hereditary neuropathy with liability to pressure palsies (HNPP) due to 17p11.2 deletion in a Korean newborn population

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder mainly due to a deletion of chromosome 17p11.2 including PMP22 (PMP22 Del HNPP). The prevalence of HNPP is estimat...

Authors: Jong Eun Park, Seung-Jae Noh, Mijin Oh, Dae-Yeon Cho, So Young Kim and Chang-Seok Ki

Pigmentary mosaicism: a review of original literature and recommendations for future handling

Pigmentary mosaicism is a term that describes varied patterns of pigmentation in the skin caused by genetic heterogeneity of the skin cells. In a substantial number of cases, pigmentary mosaicism is observed a...

Authors: Anna Boye Kromann, Lilian Bomme Ousager, Inas Kamal Mohammad Ali, Nurcan Aydemir and Anette Bygum

Programmed Sports Therapy (PST) in People with Haemophilia (PwH) “Sports Therapy Model for Rare Diseases”

Sports and exercise therapy becomes more and more integrated in the treatment plan of different diseases. Although the benefits of this therapy are of high quality evidence, e.g. in cardiovascular diseases, no...

Authors: Thomas Hilberg

TRAPPED - an insight into two sisters’ struggle to access treatment for a rare genetic disease

Medical student training is largely focused on acquiring knowledge of diseases and their management, which may leave one with a naïve perception of what is achievable in practice, particularly in the field of ...

Authors: Mariam Al-Attar

Taliglucerase alfa: safety and efficacy across 6 clinical studies in adults and children with Gaucher disease

Taliglucerase alfa is an enzyme replacement therapy (ERT) approved for treatment of adult and paediatric patients with Type 1 Gaucher disease (GD) in several countries and the first plant cell–expressed recomb...

Authors: Ari Zimran, Michael Wajnrajch, Betina Hernandez and Gregory M. Pastores

Hearing impairment in MELAS: new prospective in clinical use of microRNA, a systematic review

To evaluate the feasibility of microRNAs (miR) in clinical use to fill in the gap of current methodology commonly used to test hearing impairment in MELAS patients.

Authors: Arianna Di Stadio, Valentina Pegoraro, Laura Giaretta, Laura Dipietro, Roberta Marozzo and Corrado Angelini

Functional improvements in patients with lymphangioleiomyomatosis after sirolimus: an observational study

Sirolimus has been shown to be effective in patients with lymphangioleiomyomatosis (LAM). We wish to summarize our experience using sirolimus and its effectiveness in LAM patients.

Authors: Yongzhong Zhan, Lisha Shen, Wenshuai Xu, Xiuxiu Wu, Weihong Zhang, Jun Wang, Xue Li, Yanli Yang, Xinlun Tian and Kai-Feng Xu

Cyclosporine A does not prevent second-eye involvement in Leber’s hereditary optic neuropathy

Evaluation of the efficacy of oral cyclosporine A as a prophylactic agent in preventing second-eye involvement in Leber’s hereditary optic neuropathy (LHON) in a prospective, open-label, non-randomized, multic...

Authors: Stéphanie Leruez, Christophe Verny, Dominique Bonneau, Vincent Procaccio, Guy Lenaers, Patrizia Amati-Bonneau, Pascal Reynier, Clarisse Scherer, Adriana Prundean, Christophe Orssaud, Xavier Zanlonghi, Marie-Bénédicte Rougier, Caroline Tilikete and Dan Miléa

Quality of care in cystic fibrosis: assessment protocol of the French QIP PHARE-M

The PHARE-M care quality improvement program, modeled on the US Cystic Fibrosis Quality Improvement Program, was introduced at 14 cystic fibrosis centers (CFCs) in the French Cystic Fibrosis Network between 20...

Authors: Dominique Pougheon Bertrand, Emmanuel Nowak, Clémence Dehillotte, Lydie Lemmonier and Gilles Rault

Strategies for care quality improvement in Cystic Fibrosis

Authors: Gilles Rault and Pierre Lombrail

A quality improvement program to reduce the time on the lung transplant waiting list at the Nantes University Hospital

In 2010, the time on the lung transplant waiting list in Nantes University Hospital (NUH) was 9.2 months, compared to a French national median of about 4 months. The NUH transplant unit performs both heart and...

Authors: Isabelle Danner-Boucher, Véronique Loppinet, Aurore Boxus, Claire Dary, Anne Brigitte Lambert, Marine Prieur, Céline Vallet and Adrien Tissot

A quality improvement program for adolescents with cystic fibrosis: focus on psychosocial skills

The two pediatric cystic fibrosis centers (CFCs) in Paris (Robert Debré) and Nantes, France, have been developing therapeutic patient education (TPE) programs since 2006 and have been engaged in the pilot phas...

Authors: Michele Gérardin, Anne Pesle, Dominique Pougheon-Bertrand, Pilar Léger, Céline Vallet, Tiphaine Bihouee and Valérie David

Trans-Atlantic collaboration: applying lessons learned from the US CF Foundation quality improvement initiative

Between 2002 and 2006 France launched a national cystic fibrois (CF) newborn screening program; organized a network of specialized CF care centers; and issued CF diagnostic and treatment standards. To continue...

Authors: Kathryn A. Sabadosa, Marjorie M. Godfrey and Bruce C. Marshall

A quality improvement program to improve nutritional status of children with Cystic Fibrosis aged 2-12 years old over a 3 year period at CF center Roscoff, Brittany

The Cystic Fibrosis (CF) center in Roscoff (Brittany) has been involved in therapeutic education programs (TEP) since 2006 and took part in the pilot phase of the French quality improvement program (QIP) since...

Authors: Krista Revert, Laurence Audran, Jocelyne Pengam, Pascal Lesne and Dominique Pougheon Bertrand