eliglustat-tartrate and Cardiomyopathy--Hypertrophic

Anderson Fabry disease is a life threatening, X-linked inborn metabolic defect of the lysosomal enzyme áalpha-galactosidase A. The deficiency of alpha-galactosidase A leads to a progressive accumulation of globotriaosylceramide (Gb(3)), the major glycosphingolipid substrate of the enzyme, within vulnerable cells, tissues, and organs, including the cardiovascular system. Cardiac involvement is frequent and patients with cardiac affection develop progressive hypertrophic infiltrative cardiomyopathy, valvular abnormalities, arrhythmias, and conduction abnormalities and may develop coronary heart disease. Hemizygous male patients have no detectable alpha-galactosidase A activity, while affected heterozygous females may have normal level of alpha-galactosidase A activity. Death occurs in male patients at 45 to 50 years, about 15 to 20 years earlier than in female patients due to a vicious circle from chronic renal insufficiency, arterial hypertension, atherosclerotic lesions and cerebrovascular hemorrhage or insults, and cardiomyopathy. Cardiac involvement in hetero- and hemizygotes will be discussed as well as the influence of enzyme replacement of alpha-galactosidase A.

Topics: Adult; alpha-Galactosidase; Animals; Arrhythmias, Cardiac; Biopsy; Cardiomyopathy, Hypertrophic; Cell Line; Child; Clinical Trials as Topic; Coronary Disease; Cricetinae; Diagnosis, Differential; Echocardiography; Electrocardiography; Endocardium; Enzyme Therapy; Fabry Disease; Female; Galactose; Heart Diseases; Heart Failure; Heart Valve Diseases; Humans; Hypertrophy, Left Ventricular; Incidence; Infant, Newborn; Infusions, Intravenous; Isoenzymes; Magnetic Resonance Imaging; Male; Middle Aged; Mitral Valve Prolapse; Myocardium; Sex Factors; Smoking

Topics: Aged; alpha-Galactosidase; Cardiomyopathy, Hypertrophic; Echocardiography; Electrocardiography; Enzyme Replacement Therapy; Fabry Disease; Female; Humans; Hypertrophy, Left Ventricular; Isoenzymes

Fabry disease, an X-linked lysosomal storage disorder due to alpha-galactosidase A deficiency, leads to an accumulation of globotriaosylceramide resulting in a multisystemic disorder. The initial manifestations of the disease are not specific, leading to a delayed diagnosis. We report a patient in whom the diagnosis was obtained by family screening and the confrontation of clinical signs. We also present a 4 year follow-up under enzyme replacement therapy (agalsidase β, 1 mg/kg/14 days).

Topics: alpha-Galactosidase; Biomarkers; Cardiomyopathy, Hypertrophic; Fabry Disease; Follow-Up Studies; Genetic Testing; Humans; Isoenzymes; Male; Medical History Taking; Middle Aged; Mutation; Pedigree; Renal Insufficiency, Chronic; Treatment Outcome; Trihexosylceramides

Fabry disease is an inherited lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A. The enzyme deficiency results in accumulation of glycosphingolipids in the lysosomes n nearly all cell types and tissues leading to a multisystem disease. MANIFESTATIONS include painful crisis, angiokeratomas, corneal dystrophy, and hypohydrosis. The severe renal, cerebrovascular, and cardiac involvement is predominantly responsible for premature mortality in Fabry patients. The disease is X-linked and manifests primarily in hemizygous males but also heterozygous females can be affected. CARDIAC INVOLVEMENT is frequent in Fabry disease. Patients develop hypertrophic cardiomyopathy, arrhythmias, conduction abnormalities, and valvular abnormalities. Although Fabry disease leads to a complex clinical syndrome, there are studies indicating that manifestations can be limited to the heart. The isolated cardiac variant of Fabry disease seems to be more common than previously thought: around 3-6% of male patients with left ventricular hypertrophy seem to suffer from this disease variant.. Recent advances in molecular biology and genetic engineering have enabled the development of enzyme replacement therapy in Fabry disease. Results from two independent therapy studies are indeed promising: Infusion of the enzyme preparation seems to be well tolerated and effective in catabolizing the lipid deposits. This enzyme replacement therapy could be one of the first examples for causal treatment of left ventricular hypertrophy. Therefore, early diagnosis of hypertrophy patients with the cardiac variant of Fabry disease is important.

Topics: Adolescent; Adult; alpha-Galactosidase; Angina Pectoris; Animals; Arrhythmias, Cardiac; Cardiomyopathy, Hypertrophic; Cell Line; Child; Cricetinae; Diagnosis, Differential; Electrocardiography; Fabry Disease; Female; Genetic Engineering; Heart Diseases; Heart Valve Diseases; Heterozygote; Homozygote; Humans; Hypertrophy, Left Ventricular; Isoenzymes; Male; Randomized Controlled Trials as Topic; Sex Factors; Time Factors