Articles

Craniofacial and oral alterations in patients with Neurofibromatosis 1

Neurofibromatosis type 1 (NF1) is one of the most common inherited syndromes. The literature on craniofacial alterations associated with NF1 has been limited and partially contradictory. This review is based o...

Authors: Vivian Visnapuu, Sirkku Peltonen, Lotta Alivuotila, Risto-Pekka Happonen and Juha Peltonen

A prospective natural history study of Krabbe disease in a patient cohort with onset between 6 months and 3 years of life

Krabbe disease is a rare neurodegenerative disorder caused by a deficiency in the lysosomal enzyme galactocerebrosidase. Patients with Krabbe disease present with a variable disease course depending on their a...

Authors: Nicholas Bascou, Anthony DeRenzo, Michele D. Poe and Maria L. Escolar

Clinical presentation and outcome in infantile Sandhoff disease: a case series of 25 patients from Iranian neurometabolic bioregistry with five novel mutations

Infantile Sandhoff disease (ISD) is a GM2 gangliosidosis that is classified as a lysosomal storage disorder. The most common symptoms of affected individuals at presentation are neurologic involvement. Here we...

Authors: Ali Reza Tavasoli, Nima Parvaneh, Mahmoud Reza Ashrafi, Zahra Rezaei, Johannes Zschocke and Parastoo Rostami

Prevalence and healthcare burden of pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis (PAP) is a rare syndrome of alveolar surfactant accumulation, resulting hypoxemic respiratory failure, and increased infection risk. Despite advances in our understanding of dise...

Authors: Cormac McCarthy, Ruzan Avetisyan, Brenna C. Carey, Claudia Chalk and Bruce C. Trapnell

Key issues in Rett syndrome: emotional, behavioural and autonomic dysregulation (EBAD) - a target for clinical trials

Complex neurodevelopmental disorders need multi-disciplinary treatment approaches for optimal care. The clinical effectiveness of treatments is limited in patients with rare genetic syndromes with multisystem ...

Authors: Jatinder Singh and Paramala Santosh

Deep characterization of the anti-drug antibodies developed in Fabry disease patients, a prospective analysis from the French multicenter cohort FFABRY

Fabry disease (OMIM #301500) is an X-linked disorder caused by alpha-galactosidase A deficiency with two major clinical phenotypes: classic and non-classic of different prognosis. From 2001, enzyme replacement...

Authors: Wladimir Mauhin, Olivier Lidove, Damien Amelin, Foudil Lamari, Catherine Caillaud, Federico Mingozzi, Gaëlle Dzangué-Tchoupou, Louiza Arouche-Delaperche, Claire Douillard, Bertrand Dussol, Vanessa Leguy-Seguin, Pauline D’Halluin, Esther Noel, Thierry Zenone, Marie Matignon, François Maillot…

Improving the diagnosis of cobalamin and related defects by genomic analysis, plus functional and structural assessment of novel variants

Cellular cobalamin defects are a locus and allelic heterogeneous disorder. The gold standard for coming to genetic diagnoses of cobalamin defects has for some time been gene-by-gene Sanger sequencing of indivi...

Authors: Sandra Brasil, Fátima Leal, Ana Vega, Rosa Navarrete, María Jesús Ecay, Lourdes R. Desviat, Casandra Riera, Natàlia Padilla, Xavier de la Cruz, Mari Luz Couce, Elena Martin-Hernández, Ana Morais, Consuelo Pedrón, Luis Peña-Quintana, Miriam Rigoldi, Norma Specola…

ROHHAD and Prader-Willi syndrome (PWS): clinical and genetic comparison

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a very rare and potentially fatal pediatric disorder, the cause of which is presently unknown. ROHHAD...

Authors: Sarah F. Barclay, Casey M. Rand, Lisa Nguyen, Richard J. A. Wilson, Rachel Wevrick, William T. Gibson, N. Torben Bech-Hansen and Debra E. Weese-Mayer

The burden of congenital hyperinsulinism in the United Kingdom: a cost of illness study

Congenital hyperinsulinism (CHI) is a rare, genetic disease which causes persistent hypoglycaemia, typically in new-borns. Patients with the diffuse disease variant often require near-total surgical removal of...

Authors: Sana Eljamel, Annabel Griffiths, Jenni Evans, Indraneel Banerjee, Khalid Hussain and Richard Thompson

Fatal pitfalls in newborn screening for mitochondrial trifunctional protein (MTP)/long-chain 3-Hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency

Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency are long-chain fatty acid oxidation disorders with particularly high morbidity and mortality. Outcome...

Authors: Amelie S. Lotz-Havla, Wulf Röschinger, Katharina Schiergens, Katharina Singer, Daniela Karall, Vassiliki Konstantopoulou, Saskia B. Wortmann and Esther M. Maier

Acid ceramidase deficiency: Farber disease and SMA-PME

Acid ceramidase (ACDase) deficiency is a spectrum of disorders that includes a rare lysosomal storage disorder called Farber disease (FD) and a rare epileptic disorder called spinal muscular atrophy with progr...

Authors: Fabian P. S. Yu, Samuel Amintas, Thierry Levade and Jeffrey A. Medin

Clinical, biochemical and genetic spectrum of 70 patients with ACAD9 deficiency: is riboflavin supplementation effective?

Mitochondrial acyl-CoA dehydrogenase family member 9 (ACAD9) is essential for the assembly of mitochondrial respiratory chain complex I. Disease causing biallelic variants in ACAD9 have been reported in individua...

Authors: Birgit M. Repp, Elisa Mastantuono, Charlotte L. Alston, Manuel Schiff, Tobias B. Haack, Agnes Rötig, Anna Ardissone, Anne Lombès, Claudia B. Catarino, Daria Diodato, Gudrun Schottmann, Joanna Poulton, Alberto Burlina, An Jonckheere, Arnold Munnich, Boris Rolinski…

MicroRNAs are appropriate in mitochondrial related hearing loss? Answer to the skepticism

We aim to clarify some points that have been criticized about our previous paper “Hearing Impairment in MELAS: new prospective in clinical use of microRNA, a systematic review”.

Authors: Arianna Di Stadio and Corrado Angelini

Anatomy of the ventricular septal defect in congenital heart defects: a random association?

A ventricular septal defect (VSD) is an integral part of most congenital heart defects (CHD). To determine the prevalence of VSD in various types of CHD and the distribution of their anatomic types.

Authors: Meriem Mostefa-Kara, Lucile Houyel and Damien Bonnet

Incidence of tuberous sclerosis and age at first diagnosis: new data and emerging trends from a national, prospective surveillance study

Tuberous Sclerosis Complex (TSC) is a rare multisystem disorder. In 2012 diagnostic criteria for TSC were revised. However, data on the incidence of TSC are limited.

Authors: Daniel Ebrahimi-Fakhari, Lilian Lisa Mann, Martin Poryo, Norbert Graf, Rüdiger von Kries, Beate Heinrich, Darius Ebrahimi-Fakhari, Marina Flotats-Bastardas, Ludwig Gortner, Michael Zemlin and Sascha Meyer

Childhood hypophosphatasia: to treat or not to treat

Hypophosphatasia (HPP) is a rare inborn error of metabolism that results from dysfunction of the tissue non-specific alkaline phosphatase enzyme. Its manifestations are extremely variable, ranging from early l...

Authors: Eric T. Rush

Emotional processes and stress in children affected by hereditary angioedema with C1-inhibitor deficiency: a multicenter, prospective study

Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is characterized by recurrent edema of unpredictable frequency and severity. Stress, anxiety, and low mood are among the triggering factors most ...

Authors: Livia Savarese, Maria Bova, Raffaella De Falco, Maria Domenica Guarino, Raffaele De Luca Picione, Angelica Petraroli, Riccardo Senter, Claudia Traverso, Matteo Zabotto, Andrea Zanichelli, Eugenio Zito, Maria Alessio, Mauro Cancian, Marco Cicardi, Adriana Franzese, Roberto Perricone…

Alpha-1 antitrypsin deficiency: outstanding questions and future directions

Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition that leads to decreased circulating alpha-1 antitrypsin (AAT) levels, significantly increasing the risk of serious lung and/or liver disease...

Authors: María Torres-Durán, José Luis Lopez-Campos, Miriam Barrecheguren, Marc Miravitlles, Beatriz Martinez-Delgado, Silvia Castillo, Amparo Escribano, Adolfo Baloira, María Mercedes Navarro-Garcia, Daniel Pellicer, Lucía Bañuls, María Magallón, Francisco Casas and Francisco Dasí

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

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