Search results for "Fabry disease"

Identification of a novel mutation in the alpha-galactosidase A gene in patients with Fabry disease.

2012

Abstract Objectives Mutation analysis of the alpha-galactosidase A (GLA) gene is a valuable tool for the diagnosis of affected families. In our work, we analyze about one thousand samples per year from patients suspected of having Fabry disease (FD). Design and methods We carried out high resolution melting analysis (HRM) and DNA sequencing of all the exons of the GLA gene. We also assayed the alpha-galactosidase A activity in patients' blood. Results In some members of one family, we identified a new mutation in the GLA gene, c.614delC. This is a deletion of a single nucleotide, a cytosine, in exon 4 of the gene which causes a frameshift mutation. Conclusions Patients with the c.614delC mu…

Angiokeratoma: decision-making aid for the diagnosis of Fabry disease

2012

Isolated angiokeratomas are common benign cutaneous lesions, generally deemed unworthy of further investigation. In contrast, diffuse angiokeratomas should alert the physician to a possible diagnosis of Fabry disease, a rare X-linked lysosomal storage disorder, characterized by a-galactosidase deficiency. Glycosphingolipids accumulate in cells throughout the body resulting in progressive multi-organ failure. Difficulties are encountered when trying to interpret the significance of angiokeratomas because they may also occur in other lysosomal storage disorders and rarely in an isolated manner in Fabry disease. We present an algorithm for the classification of angiokeratomas which might prove…

Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey.

2007

Aims Anderson–Fabry disease (AFD) is an uncommon X-linked disorder caused by deficient activity of the lysosomal enzyme α-galactosidase A. The Fabry Outcome Survey is a European database designed to monitor the long-term efficacy and safety of enzyme replacement therapy (ERT) with agalsidase alfa. The aim of this study was to determine the prevalence and characteristics of cardiac disease in AFD patients. Methods and results Clinical and laboratory data were available in 714 patients from 11 countries (mean age 35 ± 17 years, 369 women, 336 treated). The prevalence of angina was 23 vs. 22%; palpitations and arrhythmias 27 vs. 26%; exertional dyspnoea 23 vs. 23%; and syncope 2 vs. 4%, in wom…

Safety of agalsidase alfa in patients with Fabry disease under 7 years

2011

Aim:  To evaluate the safety and explore the efficacy of enzyme replacement therapy (ERT) for Fabry disease with agalsidase alfa in young children enrolled in the Fabry Outcome Survey (FOS). Methods:  This retrospective chart review identified eight children (mean age = 5.0 ± 1.6 [mean ± SD]) in FOS who began treatment with agalsidase alfa (0.2 mg/kg, i.v., every other week) when <7 years old. Vital signs and adverse events were monitored throughout the study period. Glomerular filtration rate (GFR) was estimated, and left ventricular mass indexed to height2.7 (LVMi) was assessed with echocardiography. Patients received 1.2–6.7 years of treatment (mean = 4.2 years). Results:  Infusion react…

Treatment of Fabry's Disease With Migalastat: Outcome From a Prospective Observational Multicenter Study (FAMOUS).

2019

Fabry's disease (FD) is an X-linked lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme alpha-galactosidase A (alpha-Gal A) leading to intracellular accumulation of globotriaosylceramide (Gb3). Patients with amenable mutations can be treated with migalastat, a recently approved oral pharmacologic chaperone to increase endogenous alpha-Gal A activity. We assessed safety along with cardiovascular, renal, and patient-reported outcomes and disease biomarkers in a prospective observational multicenter study after 12 months of migalastat treatment under real-world conditions. Fifty-nine (28 females) patients (34 (57.6%) pretreated with enzyme replacement therapy) w…

Editorial (Thematic Issue: Anderson Fabry Disease: A Multiorgan Metabolic Disease Susceptible of Treatment)

2013

Functional characterisation of alpha-galactosidase a mutations as a basis for a new classification system in fabry disease.

2013

Fabry disease (FD) is an X-linked hereditary defect of glycosphingolipid storage caused by mutations in the gene encoding the lysosomal hydrolase α-galactosidase A (GLA, α-gal A). To date, over 400 mutations causing amino acid substitutions have been described. Most of these mutations are related to the classical Fabry phenotype. Generally in lysosomal storage disorders a reliable genotype/phenotype correlation is difficult to achieve, especially in FD with its X-linked mode of inheritance. In order to predict the metabolic consequence of a given mutation, we combined in vitro enzyme activity with in vivo biomarker data. Furthermore, we used the pharmacological chaperone (PC) 1-deoxygalacto…

A 15-Year Perspective of the Fabry Outcome Survey

2016

Abstract The Fabry Outcome Survey (FOS) is an international long-term observational registry sponsored by Shire for patients diagnosed with Fabry disease who are receiving or are candidates for therapy with agalsidase alfa (agalα). Established in 2001, FOS provides long-term data on agalα safety/efficacy and collects data on the natural history of Fabry disease, with the aim of improving clinical management. The FOS publications have helped establish prognostic and severity scores, defined the incidence of specific disease variants and implications for clinical management, described clinical manifestations in special populations, confirmed the high prevalence of cardiac morbidity, and demon…

Pharmacokinetics of agalsidase alfa in male and female patients with Fabry disease

2007

CNS manifestations of Fabry's disease

2006

Summary Background Fabry's disease is a rare hereditary lysosomal storage disease with multiorgan involvement. Deficiency of α-galactosidase A activity leads to accumulation of neutral glycosphingolipids, especially in vascular endothelial and smooth-muscle cells. Along with progressive renal and cardiac dysfunction, stroke is a major and often life-threatening burden of the disease. Cerebral vasculopathy, confirmed by neuropathological, neuroradiological, and functional studies, occurs commonly and leads to ischaemic cerebrovascular events at an early age. Recent developments Fabry's disease is an X-linked disease and women have been regarded as only mildly affected carriers. However, rese…