Orphanet Journal of Rare Diseases

http://www.ojrd.com/

List of Papers (Total 1,460)

Integrating molecular and structural findings: Wnt as a possible actor in shaping cognitive impairment in Cornelia de Lange syndrome

Cornelia de Lange Syndrome (CdLS) is a choesinopathy: a severe genetic disorder caused by mutations in the cohesin complex genes. The phenotype is characterized by typical facial dysmorphism, growth impairment and multiorgan abnormalities including brain alterations. Wnt pathway is known to play a fundamental role in central nervous system development and it has been shown that Wnt ...

Health-related quality of life among adults with diverse rare disorders

Twenty-five to 30 million Americans live with a rare disease (RD) and share challenges unique to RD. The majority of research on RDs has focused on etiology, treatment and care, while the limited health-related quality of life (HRQL) research has been restricted to single RDs, small samples, or non-validated measures. This study reports HRQL among adults with diverse RDs, and ...

Integrating molecular and structural findings: Wnt as a possible actor in shaping cognitive impairment in Cornelia de Lange syndrome

Cornelia de Lange Syndrome (CdLS) is a choesinopathy: a severe genetic disorder caused by mutations in the cohesin complex genes. The phenotype is characterized by typical facial dysmorphism, growth impairment and multiorgan abnormalities including brain alterations. Wnt pathway is known to play a fundamental role in central nervous system development and it has been shown that Wnt ...

Health-related quality of life among adults with diverse rare disorders

Twenty-five to 30 million Americans live with a rare disease (RD) and share challenges unique to RD. The majority of research on RDs has focused on etiology, treatment and care, while the limited health-related quality of life (HRQL) research has been restricted to single RDs, small samples, or non-validated measures. This study reports HRQL among adults with diverse RDs, and ...

Integrating molecular and structural findings: Wnt as a possible actor in shaping cognitive impairment in Cornelia de Lange syndrome

Cornelia de Lange Syndrome (CdLS) is a choesinopathy: a severe genetic disorder caused by mutations in the cohesin complex genes. The phenotype is characterized by typical facial dysmorphism, growth impairment and multiorgan abnormalities including brain alterations. Wnt pathway is known to play a fundamental role in central nervous system development and it has been shown that Wnt ...

Indirect estimation of the prevalence of spinal muscular atrophy Type I, II, and III in the United States

Spinal muscular atrophy (SMA) is a progressive, devastating disease and a leading inherited cause of infant mortality. The limited population-based literature is confined to small regional studies. Estimates of prevalence are needed to characterize the burden of SMA and to understand trends in prevalence by disease type as new treatments become available. The reported estimates of ...

Indirect estimation of the prevalence of spinal muscular atrophy Type I, II, and III in the United States

Spinal muscular atrophy (SMA) is a progressive, devastating disease and a leading inherited cause of infant mortality. The limited population-based literature is confined to small regional studies. Estimates of prevalence are needed to characterize the burden of SMA and to understand trends in prevalence by disease type as new treatments become available. The reported estimates of ...

Integrating molecular and structural findings: Wnt as a possible actor in shaping cognitive impairment in Cornelia de Lange syndrome

Cornelia de Lange Syndrome (CdLS) is a choesinopathy: a severe genetic disorder caused by mutations in the cohesin complex genes. The phenotype is characterized by typical facial dysmorphism, growth impairment and multiorgan abnormalities including brain alterations. Wnt pathway is known to play a fundamental role in central nervous system development and it has been shown that Wnt ...

Measuring what matters to rare disease patients – reflections on the work by the IRDiRC taskforce on patient-centered outcome measures

Our ability to evaluate outcomes which genuinely reflect patients’ unmet needs, hopes and concerns is of pivotal importance. However, much current clinical research and practice falls short of this objective by selecting outcome measures which do not capture patient value to the fullest. In this Opinion, we discuss Patient-Centered Outcomes Measures (PCOMs), which have the ...

A web-based collection of genotype-phenotype associations in hereditary recurrent fevers from the Eurofever registry

Hereditary recurrent fevers (HRF) are a group of rare monogenic diseases leading to recurrent inflammatory flares. A large number of variants has been described for the four genes associated with the best known HRF, namely MEFV, NLRP3, MVK, TNFRSF1A. The Infevers database ( http://fmf.igh.cnrs.fr/ISSAID/infevers ) is a large international registry collecting variants reported in ...

KH176 under development for rare mitochondrial disease: a first in man randomized controlled clinical trial in healthy male volunteers

Mitochondrial disorders are a clinically, biochemically and genetically heterogeneous group of multi-system diseases, with an unmet medical need for treatment. KH176 is an orally bio-available small molecule under development for the treatment of mitochondrial(−related) diseases. The compound is a member of a new class of drugs, acting as a potent intracellular redox-modulating ...

Unmet clinical needs and burden in Angelman syndrome: a review of the literature

Angelman syndrome (AS) is a rare disorder with a relatively well-defined phenotype. Despite this, very little is known regarding the unmet clinical needs and burden of this condition, especially with regard to some of the most prevalent clinical features—movement disorders, communication impairments, behavior, and sleep. A targeted literature review using electronic medical ...

The complete European guidelines on phenylketonuria: diagnosis and treatment

Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism caused by deficiency in the enzyme phenylalanine hydroxylase that converts phenylalanine into tyrosine. If left untreated, PKU results in increased phenylalanine concentrations in blood and brain, which cause severe intellectual disability, epilepsy and behavioural problems. PKU management ...

Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter outcome survey (HOS)

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare, X-linked disorder caused by deficient activity of the enzyme iduronate-2-sulfatase (I2S). Treatment is available in the form of enzyme replacement therapy (ERT) with recombinant I2S. Clinical outcomes following ≥3 years of ERT with idursulfase were investigated in a broad population of patients with MPS II enrolled ...

Transient yellow discoloration of the nails for differential diagnosis with yellow nail syndrome

A differential diagnosis must be made between transient yellow discoloration of the nails and yellow nail syndrome. We highlight some practical aspects of yellow nail discoloration.

A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhood

Based on the hypothesis of a brain energy deficit, we investigated the safety and efficacy of triheptanoin on paroxysmal episodes in patients with alternating hemiplegia of childhood due to ATP1A3 mutations. We conducted a randomized, double-blind, placebo-controlled crossover study of triheptanoin, at a target dose corresponding to 30% of daily calorie intake, in ten patients with ...

The impact of lipoprotein lipase deficiency on health-related quality of life: a detailed, structured, qualitative study

Lipoprotein lipase deficiency (LPLD) is an autosomal recessive inherited disorder caused by loss-of-function mutations in genes involved in the lipoprotein lipase pathway. It is characterised by chylomicronaemia, severe hypertriglyceridaemia and an increased risk of recurrent pancreatitis that often requires hospitalisation. This research aimed to improve our understanding of the ...

A quantitative assessment of the evolution of cerebellar syndrome in children with phosphomannomutase-deficiency (PMM2-CDG)

We aim to delineate the progression of cerebellar syndrome in children with phosphomannomutase-deficiency (PMM2-CDG) using the International Cooperative Ataxia Rating Scale (ICARS). We sought correlation between cerebellar volumetry and clinical situation. We prospectively evaluated PMM2-CDG patients aged from 5 to 18 years through ICARS at two different time points set apart by at ...

Evaluation of pre-symptomatic nitisinone treatment on long-term outcomes in Tyrosinemia type 1 patients: a systematic review

Tyrosinemia type 1 (TYR1) is a rare autosomal recessive disorder of amino acid metabolism that is fatal without treatment. With medication (nitisinone) and dietary restrictions outcomes are improved. We conducted a systematic review to investigate if treatment with nitisinone following screening provides better long-term outcomes than treatment with nitisinone following symptomatic ...

Prevalence of Amyloidosis in Korea

The aim of this study was to assess in amyloidosis prevalence in Korea between 2006 and 2015. Primary diagnoses related to amyloidosis, regardless of subtype, were collected from the Korean National Health Insurance Service from 2006 through 2015. Overall, the age-standardized prevalence of amyloidosis was 0.93 (95% confidence interval (CI) 0.81, 1.04) persons per 100,000 persons ...

Exome sequences versus sequential gene testing in the UK highly specialised Service for Limb Girdle Muscular Dystrophy

Limb girdle muscular dystrophies are a group of rare and genetically heterogeneous diseases that share proximal weakness as a common feature; however they are often lacking very specific phenotypic features to allow an accurate differential diagnosis based on the clinical signs only, limiting the diagnostic rate using phenotype driven genetic testing. Next generation sequencing ...

Fabry disease and incidence of cancer

Fabry disease is an X-linked lysosomal storage disorder caused by deficient activity of α-galactosidase A and the resulting accumulation of the glycosphingolipid globotriaosylceramide (Gb3) and its derivatives, including globotriaosylsphingosine (Lyso-Gb3). Increased cellular and plasma levels of Gb3 and Lyso-Gb3 affect multiple organs, with specific clinical consequences for the ...

Lucerastat, an iminosugar with potential as substrate reduction therapy for glycolipid storage disorders: safety, tolerability, and pharmacokinetics in healthy subjects

Background Lucerastat, an inhibitor of glucosylceramide synthase, has the potential to restore the balance between synthesis and degradation of glycosphingolipids in glycolipid storage disorders such as Gaucher disease and Fabry disease. The safety, tolerability, and pharmacokinetics of oral lucerastat were evaluated in two separate randomized, double-blind, placebo-controlled, ...