Effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic acidurias

Hyperammonaemia is a key sign of decompensation in organic acidurias (OAs) and can contribute to severe neurological complications, thus requiring rapid treatment.

Authors: Anupam Chakrapani, Vassili Valayannopoulos, Nuria García Segarra, Mireia Del Toro, Maria Alice Donati, Angeles García-Cazorla, María Julieta González, Celine Plisson and Vincenzo Giordano

Target achievement and cardiovascular event rates with Lomitapide in homozygous Familial Hypercholesterolaemia

Homozygous familial hypercholesterolaemia (HoFH) is characterized by a markedly increased risk of premature cardiovascular (CV) events and cardiac death. Lomitapide reduces low-density lipoprotein cholesterol ...

Authors: Dirk J. Blom, Marina Cuchel, Miranda Ager and Helen Phillips

How to address the challenges of evaluating treatment benefits-risks in rare diseases? A convergent mixed methods approach applied within a Merkel cell carcinoma phase 2 clinical trial

Demonstrating treatment benefits within clinical trials in the context of rare diseases is often methodologically and practically challenging. Mixed methods research offers an approach to overcome these challe...

Authors: Murtuza Bharmal, Isabelle Guillemin, Alexia Marrel, Benoit Arnould, Jérémy Lambert, Meliessa Hennessy and Fatoumata Fofana

Clinical and genetic characteristics of Chinese patients with familial or sporadic pediatric cataract

Pediatric cataract is a clinically and genetically heterogeneous disease which is a significant cause of lifelong visual impairment and treatable blindness. Our study aims to investigate the genotype spectrum ...

Authors: Jingyan Li, Yunji Leng, Shirui Han, Lulu Yan, Chaoxia Lu, Yang Luo, Xue Zhang and Lihua Cao

What’s new in pontocerebellar hypoplasia? An update on genes and subtypes

Pontocerebellar hypoplasia (PCH) describes a rare, heterogeneous group of neurodegenerative disorders mainly with a prenatal onset. Patients have severe hypoplasia or atrophy of cerebellum and pons, with varia...

Authors: Tessa van Dijk, Frank Baas, Peter G. Barth and Bwee Tien Poll-The

Exon skipping for Duchenne muscular dystrophy: a systematic review and meta-analysis

Exon skipping has been considered a promising therapeutic approach for Duchenne muscular dystrophy (DMD). Eteplirsen received conditional approval in the United States in 2016. To date, no systematic reviews o...

Authors: Yuko Shimizu-Motohashi, Terumi Murakami, En Kimura, Hirofumi Komaki and Norio Watanabe

Distinguishing neurocognitive deficits in adult patients with NP-C from early onset Alzheimer’s dementia

Niemann-Pick disease type C (NP-C) is a rare, progressive neurodegenerative disease caused by mutations in the NPC1 or the NPC2 gene. Neurocognitive deficits are common in NP-C, particularly in patients with the ...

Authors: Andreas Johnen, Matthias Pawlowski and Thomas Duning

Food as a trigger for abdominal angioedema attacks in patients with hereditary angioedema

Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is a rare inherited disease. In most HAE-affected subjects, defined trigger factors precede angioedema attacks. Mechanisms of how trigger factors...

Authors: Urs C. Steiner, Lea Kölliker, Christina Weber-Chrysochoou, Peter Schmid-Grendelmeier, Elsbeth Probst, Walter A. Wuillemin and Arthur Helbling

Clinical characteristics and surgical history of Taiwanese patients with mucopolysaccharidosis type II: data from the hunter outcome survey (HOS)

Mucopolysaccharidosis type II (MPS II) is the most frequently occurring MPS in Taiwan, with an incidence of 2.05 per 100,000 live male births, but little is known about clinical characteristics and surgical hi...

Authors: Hsiang-Yu Lin, Chih-Kuang Chuang, Ming-Ren Chen, Shio Jean Lin, Pao Chin Chiu, Dau-Ming Niu, Fuu-Jen Tsai, Wuh-Liang Hwu, Yin-Hsiu Chien, Ju-Li Lin and Shuan-Pei Lin

Retinal and optic nerve degeneration in α-mannosidosis

α-mannosidosis is a rare, autosomal-recessive, lysosomal storage disease caused by a deficient activity of α-mannosidase. Typical symptoms include intellectual, motor and hearing impairment, facial coarsening,...

Authors: Juliane Matlach, Thea Zindel, Yasmina Amraoui, Laila Arash-Kaps, Julia B. Hennermann and Susanne Pitz

Next generation phenotyping using narrative reports in a rare disease clinical data warehouse

Secondary use of data collected in Electronic Health Records opens perspectives for increasing our knowledge of rare diseases. The clinical data warehouse (named Dr. Warehouse) at the Necker-Enfants Malades Ch...

Authors: Nicolas Garcelon, Antoine Neuraz, Rémi Salomon, Nadia Bahi-Buisson, Jeanne Amiel, Capucine Picard, Nizar Mahlaoui, Vincent Benoit, Anita Burgun and Bastien Rance

MicroRNAs are inappropriate for characterising hearing impairment in mitochondrial disorders

Authors: Josef Finsterer and Sinda Zarrouk-Mahjoub

Status of newborn screening and follow up investigations for Mucopolysaccharidoses I and II in Taiwan

Mucopolysaccharidoses (MPS) are lysosomal storage diseases in which mutations of genes encoding for lysosomal enzymes cause defects in the degradation of glycosaminoglycans (GAGs). The accumulation of GAGs in ...

Authors: Chih-Kuang Chuang, Hsiang-Yu Lin, Tuan-Jen Wang, You-Hsin Huang, Min-Ju Chan, Hsuan-Chieh Liao, Yun-Ting Lo, Li-Yun Wang, Ru-Yi Tu, Yi-Ya Fang, Tzu-Lin Chen, Hui-Chen Ho, Chuan-Chi Chiang and Shuan-Pei Lin

A review of scoring systems for ocular involvement in chronic cutaneous bullous diseases

Epidermolysis bullosa (EB) and autoimmune blistering diseases (AIBD) describe a group of rare chronic dermatoses characterized by cutaneous fragility and blistering. Although uncommon, significant ocular surfa...

Authors: Brendon W. H. Lee, Jeremy C. K. Tan, Melissa Radjenovic, Minas T. Coroneo and Dedee F. Murrell

Enzyme replacement therapy reduces the risk for wheelchair dependency in adult Pompe patients

Pompe disease is a rare metabolic myopathy. In adult patients, progressive weakness of limb-girdle and respiratory muscles often leads to wheelchair and respirator dependency. Clinical studies have shown enzym...

Authors: Jan C. van der Meijden, Michelle E. Kruijshaar, Dimitris Rizopoulos, Pieter A. van Doorn, Nadine A. M. E. van der Beek and Ans T. van der Ploeg

Improving the analysis of composite endpoints in rare disease trials

Composite endpoints are recommended in rare diseases to increase power and/or to sufficiently capture complexity. Often, they are in the form of responder indices which contain a mixture of continuous and bina...

Authors: Martina McMenamin, Anna Berglind and James M. S. Wason

Severe hepatopathy and neurological deterioration after start of valproate treatment in a 6-year-old child with mitochondrial tryptophanyl-tRNA synthetase deficiency

The first subjects with deficiency of mitochondrial tryptophanyl-tRNA synthetase (WARS2) were reported in 2017. Their clinical characteristics can be subdivided into three phenotypes (neonatal phenotype, sever...

Authors: Elise Vantroys, Joél Smet, Arnaud V. Vanlander, Sarah Vergult, Ruth De Bruyne, Frank Roels, Hedwig Stepman, Herbert Roeyers, Björn Menten and Rudy Van Coster

Mineralization of alpha-1-antitrypsin inclusion bodies in Mmalton alpha-1-antitrypsin deficiency

Alpha-1-antitrypsin (AAT) deficiency (AATD) of Z, Mmalton, Siiyama type is associated with liver storage of the mutant proteins and liver disease. The Z variant can be diagnosed on isoelectric focusing (IEF) w...

Authors: Francesco Callea, Isabella Giovannoni, Paola Francalanci, Renata Boldrini, Gavino Faa, Daniela Medicina, Valerio Nobili, Valeer J. Desmet, Kamal Ishak, Kuniaki Seyama and Emanuele Bellacchio

A total pleural covering of absorbable cellulose mesh prevents pneumothorax recurrence in patients with Birt-Hogg-Dubé syndrome

Birt-Hogg-Dubé syndrome (BHDS) is a recently recognized inherited multiple cystic lung disease causing recurrent pneumothoraces. Similarly to the lesions in patients with lymphangioleiomyomatosis (LAM), the pu...

Authors: Teruaki Mizobuchi, Masatoshi Kurihara, Hiroki Ebana, Sumitaka Yamanaka, Hideyuki Kataoka, Shouichi Okamoto, Etsuko Kobayashi, Toshio Kumasaka and Kuniaki Seyama

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

Beneath the floor: re-analysis of neurodevelopmental outcomes in untreated Hurler syndrome

Hurler syndrome (MPS IH), the severe, neurodegenerative form of type one mucopolysaccharidosis, is associated with rapid neurocognitive decline during toddlerhood and multi-system dysfunction. It is now standa...

Authors: Elsa G. Shapiro, Chester B. Whitley and Julie B. Eisengart

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

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