Search results for "globotriaosylceramide"
showing 10 items of 25 documents
Cutaneous complications of Anderson-Fabry disease.
2013
Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by a defect in the -galactosidase A gene, which leads to the deficiency of the hydrolytic enzyme -galactosidase A. The consequent inability to catabolize glycosphingolipids causes progressive accumulation of globotriaosylceramide in the vascular endothelium throughout the body. Fatalities in the classical phenotype may usually occur as a consequence of cerebral, cardiac or renal disease. Dermatological manifestations are a relevant feature of Fabry disease and include angiokeratomas, telangiectasiae, lymphedema, anhidrosis or hypohidrosis and pseudo-acromegalic facial appearance. The actual causal treatment for Fabry …
Enzyme replacement therapy with agalsidase alfa in children with Fabry disease.
2006
Aim: To assess the effects of enzyme replacement therapy (ERT) in children with Fabry disease. Methods: Safety and efficacy of ERT with agalsidase alfa, 0.2 mg/kg infused over 40 minutes every 2 weeks for 23 weeks, were studied in a multicentre open-label trial in nine boys and four girls. Median age at the start of the study was 11.0 years (range 3.5–18 years). Results: Fifty-four adverse events were reported in 11 patients. No serious adverse events related to ERT were reported. Twelve of the 54 adverse events were considered possibly or probably related to ERT. Infusion reactions (8 mild, 3 moderate) occurred in four boys, in seven infusions. One boy developed IgG antibodies, although he…
Treatment of Fabry Disease management with migalastat-outcome from a prospective 24 months observational multicenter study (FAMOUS).
2020
Abstract Aims Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (GLA/AGAL), resulting in the lysosomal accumulation of globotriaosylceramide (Gb3). Patients with amenable GLA mutations can be treated with migalastat, an oral pharmacological chaperone increasing endogenous AGAL activity. In this prospective observational multicentre study, safety as well as cardiovascular, renal, and patient-reported outcomes and disease biomarkers were assessed after 12 and 24 months of migalastat treatment under ‘real-world’ conditions. Methods and results A total of 54 patients (26 females) (33 of these [61.1%] pre-treated with en…
Clinical manifestations of Fabry disease in children: data from the Fabry Outcome Survey.
2006
Background Fabry disease is a rare X-linked disorder caused by deficient activity of the enzyme alpha-galactosidase A. This produces progressive lysosomal accumulation of globotriaosylceramide throughout the body, leading to organ failure and premature death. Aim Here, we present the clinical manifestations of Fabry disease in children enrolled in FOS--the Fabry Outcome Survey--a European database of the natural history of Fabry disease and the effects of enzyme replacement therapy with agalsidase alfa (Replagal). Methods Currently, there are 545 patients in FOS, from 11 European countries. We analysed the baseline demographic and clinical characteristics of 82 of these patients (40 boys, 4…
Fabry disease: enzyme replacement therapy
2003
Fabry disease is a multisystem disorder associated with wide variability in clinical expression. Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase A. The enzyme defect leads to the systemic accumulation of glycosphingolipids with alpha-galactosyl moieties consisting predominantly of globotriaosylceramide, galabiosylceramide and two additional glycosphingolipids. Four hemizygotes patients with a family history of Fabry disease and deficiency of the enzyme alpha-galactosidase A were selected. Each patient received purified alpha-galactosidase by intravenous infusion (0.2 mg/kg). The infusion was administered every 2 weeks, for 40 min, for a …
Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey.
2004
Background Fabry disease is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme α-galactosidase A. Progressive accumulation of the substrate globotriaosylceramide in cells throughout the body leads to major organ failure and premature death. In response to the recent introduction of enzyme replacement therapy, the Fabry Outcome Survey (FOS) was established to pool data from European clinics on the natural history of this little-known disease and to monitor the long-term efficacy and safety of treatment. This paper presents the first analysis of the FOS database and provides essential baseline data against which the effects of enzyme replacement can be measured. De…
Frequency of Fabry disease in patients with small-fibre neuropathy of unknown aetiology: a pilot study
2010
Background: Early occurrence of small-fibre neuropathy (SFN) is a common feature of Fabry disease (FD) – an X-linked storage disorder caused by reduced activity of the α-galactosidase A (α-GAL). Although SFN may result from different disorders, the cause is often unclear. Therefore, we investigated the frequency of FD in patients with SFN of unknown aetiology. Methods: Patients with idiopathic SFN, established by sensory quantitative testing and/or skin biopsy, were examined for mutations in the α-GAL gene. Where mutations in the α-GAL gene were identified, levels of globotriaosylceramide (Gb3) were measured in urine and blood and the α-GAL activity was evaluated. When new mutations were …
Cerebrovascular involvement in fabry disease: current status of knowledge.
2014
Fabry disease (FD) is a rare and highly debilitating lysosomal storage disorder that results from a total lack of, or deficiency in, the enzyme α-galactosidase A (α-Gal A) because of mutations in the GLA gene.1 FD is inherited as an X-linked trait; many of the male patients develop a classic severe phenotype with early onset of symptoms, whereas heterozygous females exhibit phenotypes ranging from asymptomatic to major involvement of vital organs.2 Most families inherit private mutations; to date, >600 mutations have been identified and are listed in the online FD database (Fabry-database.org).3 The deficiency in α-Gal A causes the accumulation of globotriaosylceramide (GL-3; also abbreviat…
Pathogenesis and molecular mechanisms of anderson–fabry disease and possible new molecular addressed therapeutic strategies
2021
Anderson–Fabry disease (AFD) is a rare disease with an incidenceof approximately 1:117,000 male births. Lysosomal accumulation of globotriaosylceramide (Gb3) is the element characterizing Fabry disease due to a hereditary deficiency α-galactosidase A (GLA) enzyme. The accumulation of Gb3 causes lysosomal dysfunction that compromises cell signaling pathways. Deposition of sphingolipids occurs in the autonomic nervous system, dorsal root ganglia, kidney epithelial cells, vascular system cells, and myocardial cells, resulting in organ failure. This manuscript will review the molecular pathogenetic pathways involved in Anderson–Fabry disease and in its organ damage. Some studies reported that i…
Fabry nephropathy: 5 years of enzyme replacement therapy-a short review.
2007
Fabry disease is an X-linked lysosomal storage disease, resulting from a deficiency of the enzyme α-galactosidase A and subsequent cellular storage of the enzyme substrate globotriaosylceramide (Gb3) [1]. Estimates of the incidence of Fabry disease vary markedly, from 1:<5000 male births in a newborn screening study in Italy [2] to 1:117 000 male births in Australia [3] and 1:833 000 male births in northern Portugal [4]. In general, hemizygous males are more severely affected than heterozygous females. In males, life expectancy is reduced by an average of 20 years [5] and in females by 15 years [6]. Although males tend to suffer symptoms earlier than females, both boys and girls can be affe…