Articles

Transcriptome level analysis in Rett syndrome using human samples from different tissues

The mechanisms of neuro-genetic disorders have been mostly investigated in the brain, however, for some pathologies, transcriptomic analysis in multiple tissues represent an opportunity and a challenge to unde...

Authors: Stephen Shovlin and Daniela Tropea

Challenges of palliative care in children with inborn metabolic diseases

Our objective was to evaluate children with metabolic diseases in paediatric palliative home care (PPC) and the process of decision-making. This study was conducted as single-centre retrospective cohort study ...

Authors: Jessica I. Hoell, Jens Warfsmann, Felix Distelmaier, Arndt Borkhardt, Gisela Janßen and Michaela Kuhlen

Molecular diagnosis of anti-laminin 332 (epiligrin) mucous membrane pemphigoid

Mucous membrane pemphigoid is a group of chronic subepithelial autoimmune blistering diseases that mainly affect mucous membranes. Laminin 332-specific autoantibodies are present in approximately 1/3 of the pa...

Authors: Roxana Chiorean, Sorina Danescu, Oana Virtic, Mayson B. Mustafa, Adrian Baican, Annette Lischka, Takashi Hashimoto, Yoshinobu Kariya, Manuel Koch and Cassian Sitaru

Neurocognitive and somatic stabilization in pediatric patients with severe Mucopolysaccharidosis Type I after 52 weeks of intravenous brain-penetrating insulin receptor antibody-iduronidase fusion protein (valanafusp alpha): an open label phase 1-2 trial

Mucopolysaccharidosis (MPS) Type I (MPSI) is caused by mutations in the gene encoding the lysosomal enzyme, α-L-iduronidase (IDUA), and a majority of patients present with severe neurodegeneration and cognitiv...

Authors: Roberto Giugliani, Luciana Giugliani, Fabiano de Oliveira Poswar, Karina Carvalho Donis, Amauri Dalla Corte, Mathias Schmidt, Ruben J. Boado, Igor Nestrasil, Carol Nguyen, Steven Chen and William M. Pardridge

Comprehensive genetic characteristics of dystrophinopathies in China

Dystrophinopathies are a set of severe and incurable X-linked neuromuscular disorders caused by mutations in the dystrophin gene (DMD). These mutations form a complex spectrum. A national registration network is ...

Authors: Peipei Ma, Shu Zhang, Hao Zhang, Siying Fang, Yuru Dong, Yan Zhang, Weiwei Hao, Shiwen Wu and Yuying Zhao

Long-term safety and efficacy of pegvaliase for the treatment of phenylketonuria in adults: combined phase 2 outcomes through PAL-003 extension study

Deficiency of phenylalanine hydroxylase causes phenylketonuria (PKU) with elevated phenylalanine (Phe) levels and associated neuropsychiatric and neurocognitive symptoms. Pegvaliase (PEGylated phenylalanine am...

Authors: Nicola Longo, Roberto Zori, Melissa P. Wasserstein, Jerry Vockley, Barbara K. Burton, Celeste Decker, Mingjin Li, Kelly Lau, Joy Jiang, Kevin Larimore and Janet A. Thomas

Amyloidosis due to TTR mutations in Mexico with 4 distincts genotypes in the index cases

Transthyretin-related hereditary amyloidosis (ATTR) is a systemic disease characterized by extracellular deposits of amyloid due to the autosomal dominant inheritance of a mutation in the TTR gene (18q12.1). A...

Authors: Alejandra González-Duarte, Karla Cárdenas-Soto, Carlo Enrico Bañuelos, Omar Fueyo, Carolina Dominguez, Benjamín Torres and Carlos Cantú-Brito

17p13.3 genomic rearrangement in a Chinese family with split-hand/foot malformation with long bone deficiency: report of a complicated duplication with marked variation in phenotype

Split hand/foot malformation (SHFM) is a genetically heterogeneous limb malformation with variable expressivity. SHFM with tibia or femur aplasia is called SHFM with long bone deficiency (SHFLD). 17p13.3 dupli...

Authors: Yuqi Shen, Nuo Si, Zhe Liu, Fang Liu, Xiaolu Meng, Ying Zhang and Xue Zhang

6-minute walk test as a measure of disease progression and fatigability in a cohort of individuals with RYR1-related myopathies

RYR1-related Myopathies (RYR1-RM) comprise a group of rare neuromuscular diseases (NMDs) occurring in approximately 1/90000 people in the US pediatric population. RYR1-RM result from pathogenic mutations in the r...

Authors: Jessica W. Witherspoon, Ruhi P. Vasavada, Melissa R. Waite, Monique Shelton, Irene C. Chrismer, Paul G. Wakim, Minal S. Jain, Carsten G. Bönnemann and Katherine G. Meilleur

Using a meta-narrative literature review and focus groups with key stakeholders to identify perceived challenges and solutions for generating robust evidence on the effectiveness of treatments for rare diseases

For many rare diseases, strong analytic study designs for evaluating the efficacy and effectiveness of interventions are challenging to implement because of small, geographically dispersed patient populations ...

Authors: Kylie Tingley, Doug Coyle, Ian D. Graham, Lindsey Sikora, Pranesh Chakraborty, Kumanan Wilson, John J. Mitchell, Sylvia Stockler-Ipsiroglu and Beth K. Potter

Carbohydrate status in patients with phenylketonuria

In patients with phenylketonuria (PKU), a low-phenylalanine (Phe) diet supplemented with low-protein foods and a Phe-free amino acid mixture favors a dietary intake rich in carbohydrates, but little is known a...

Authors: María L. Couce, Paula Sánchez-Pintos, Isidro Vitoria, María-José De Castro, Luís Aldámiz-Echevarría, Patricia Correcher, Ana Fernández-Marmiesse, Iria Roca, Alvaro Hermida, Miguel Martínez-Olmos and Rosaura Leis

Longitudinal hearing loss in Wolfram syndrome

Wolfram syndrome (WFS) is a rare autosomal recessive disease with clinical manifestations of diabetes mellitus (DM), diabetes insipidus (DI), optic nerve atrophy (OA) and sensorineural hearing loss (SNHL). Alt...

Authors: Roanne Karzon, Anagha Narayanan, Ling Chen, Judith E. C. Lieu and Tamara Hershey

Status of nutrients important in brain function in phenylketonuria: a systematic review and meta-analysis

Despite early and ongoing dietary management with a phe-restricted diet, suboptimal neuropsychological function has been observed in PKU. The restrictive nature of the PKU diet may expose patients to sub-optim...

Authors: Gina A. Montoya Parra, Rani H. Singh, Aysun Cetinyurek-Yavuz, Mirjam Kuhn and Anita MacDonald

Pathophysiology of carotid-cavernous fistulas in vascular Ehlers-Danlos syndrome: a retrospective cohort and comprehensive review

Vascular Ehlers-Danlos syndrome (vEDS) is a rare condition characterized by connective tissue fragility. Direct spontaneous carotid-cavernous fistula (sCCF) is reportedly pathognomonic of vEDS. We conducted th...

Authors: Salma Adham, Denis Trystram, Juliette Albuisson, Valérie Domigo, Anne Legrand, Xavier Jeunemaitre and Michael Frank

Thymectomy in nonthymomatous myasthenia gravis - systematic review and meta-analysis

The objective of this study is to evaluate by means of a systematic review, the efficacy of thymectomy as compared to medical treatment for non-thymomatous myasthenia gravis (MG).

Authors: Antônio J. M. Cataneo, Gilmar Felisberto Jr. and Daniele C. Cataneo

Increased extracellular matrix deposition during chondrogenic differentiation of dental pulp stem cells from individuals with neurofibromatosis type 1: an in vitro 2D and 3D study

Neurofibromatosis 1 (NF1) presents a wide range of clinical manifestations, including bone alterations. Studies that seek to understand cellular and molecular mechanisms underlying NF1 orthopedic problems are ...

Authors: Paula Nascimento Almeida, Deuilton do Nascimento Barboza, Eloá Borges Luna, Maria Clara de Macena Correia, Rhayra Braga Dias, Ana Caroline Siquara de Sousa, Maria Eugenia Leite Duarte, Maria Isabel Doria Rossi and Karin Soares Cunha

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

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

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

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

MicroRNAs are inappropriate for characterising hearing impairment in mitochondrial disorders

Authors: Josef Finsterer and Sinda Zarrouk-Mahjoub

Recessive mutations in ATP8A2 cause severe hypotonia, cognitive impairment, hyperkinetic movement disorders and progressive optic atrophy

ATP8A2 mutations have recently been described in several patients with severe, early-onset hypotonia and cognitive impairment. The aim of our study was to characterize the clinical phenotype of patients with ATP8...

Authors: Hugh J. McMillan, Aida Telegrafi, Amanda Singleton, Megan T. Cho, Daniel Lelli, Francis C. Lynn, Julie Griffin, Alexander Asamoah, Tuula Rinne, Corrie E. Erasmus, David A. Koolen, Charlotte A. Haaxma, Boris Keren, Diane Doummar, Cyril Mignot, Islay Thompson…

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

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

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

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

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

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

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

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

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

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

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