globotriaosylceramide and Arrhythmias--Cardiac

Fabry disease is a rare, progressive, X-linked inherited storage disorder due to absent or deficient of lysosomal alfa galactosidase A activity. Deficient activity of alfa-galactosidase A results in progressive accumulation of globotriaosylceramide in a variety of tissues and organs including myocardium, kidney and nerve system. This disorder predominantly affects males; however, female heterozygotes may also be affected with a less severe clinical picture. Classic Fabry disease is usually diagnosed in early age of childhood because of multiorgan involvement whereas cardiac and renal variants of Fabry are manifested in 30-50 years of age because of late onset of clinical picture in which other organs involvement are uncommon. Although Fabry is known as a very rare disease, its prevalence is reported to be higher in patients with ventricular hypertrophy, chronic kidney disease and cryptogenic stroke. From the cardiology point of view, the most important key finding of the disease is unexplained ventricular hypertrophy. However, in clinical practice, ventricular hypertrophy is usually thought to be due to hypertrophic cardiomyopathy in the absence of hypertension or aortic stenosis and Fabry disease is often undiagnosed or overlooked. Early diagnosis and enzyme replacement therapy have been shown to significantly improve prognosis. The aim of this paper is to provide a comprehensive review including epidemiology, prognosis, clinical presentation, diagnosis and therapeutic approaches of cardiac variant of Fabry based on the available data in the literature.

Topics: Age of Onset; alpha-Galactosidase; Arrhythmias, Cardiac; Cardiomegaly; Early Diagnosis; Echocardiography; Electrocardiography; Electrocardiography, Ambulatory; Enzyme Replacement Therapy; Fabry Disease; Female; Heart Diseases; Heterozygote; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Pedigree; Prognosis; Sex Factors; Symptom Assessment; Trihexosylceramides

Fabry disease is a metabolic disorder without a specific treatment, caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-gal A). Most patients experience debilitating neuropathic pain and premature mortality because of renal failure, cardiovascular disease, or cerebrovascular disease.. To evaluate the safety and efficacy of intravenous alpha-gal A for Fabry disease.. Double-blind placebo-controlled trial conducted from December 1998 to August 1999 at the Clinical Research Center of the National Institutes of Health.. Twenty-six hemizygous male patients, aged 18 years or older, with Fabry disease that was confirmed by alpha-gal A assay.. A dosage of 0.2 mg/kg of alpha-gal A, administered intravenously every other week (12 doses total).. Effect of therapy on neuropathic pain while without neuropathic pain medications measured by question 3 of the Brief Pain Inventory (BPI).. Mean (SE) BPI neuropathic pain severity score declined from 6.2 (0.46) to 4.3 (0.73) in patients treated with alpha-gal A vs no significant change in the placebo group (P =.02). Pain-related quality of life declined from 3.2 (0.55) to 2.1 (0.56) for patients receiving alpha-gal A vs 4.8 (0.59) to 4.2 (0.74) for placebo (P =.05). In the kidney, glomeruli with mesangial widening decreased by a mean of 12.5% for patients receiving alpha-gal vs a 16.5% increase for placebo (P =.01). Mean inulin clearance decreased by 6.2 mL/min for patients receiving alpha-gal A vs 19.5 mL/min for placebo (P =.19). Mean creatinine clearance increased by 2.1 mL/min (0.4 mL/s) for patients receiving alpha-gal A vs a decrease of 16.1 mL/min (0.3 mL/s) for placebo (P =.02). In patients treated with alpha-gal A, there was an approximately 50% reduction in plasma glycosphingolipid levels, a significant improvement in cardiac conduction, and a significant increase in body weight.. Intravenous infusions of alpha-gal A are safe and have widespread therapeutic efficacy in Fabry disease.

Topics: Adult; alpha-Galactosidase; Analysis of Variance; Arrhythmias, Cardiac; Body Weight; Double-Blind Method; Drug Administration Schedule; Fabry Disease; Heart Rate; Humans; Infusions, Intravenous; Kidney Function Tests; Male; Pain Measurement; Trihexosylceramides

Topics: alpha-Galactosidase; Arrhythmias, Cardiac; Biopsy; Cardiomyopathies; Fabry Disease; Humans; Lysosomes; Trihexosylceramides

Topics: Algorithms; Arrhythmias, Cardiac; Cardiomyopathy, Hypertrophic; Electrocardiography; Enzyme Therapy; Fabry Disease; Female; Fibrosis; Humans; Hypertrophy, Left Ventricular; Male; Myocardium; Sex Factors; Trihexosylceramides; Vascular Diseases