The heart in Anderson Fabry disease.
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.
Kampmann
Christoph
C
Universitätskinderklinik Johannes-Gutenberg-Universität Langenbeckstr. 1 55131 Mainz, Germany. christoph.kampmann@uni-mainz.de
Wiethoff
Christiane M
CM
Perrot
A
A
Beck
Michael
M
Dietz
Rainer
R
Osterziel
Karl J
KJ
D000328:Adult; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000209:etiology; D001706:Biopsy; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000209:etiology; D002460:Cell Line; D002648:Child; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000209:etiology; D006224:Cricetinae; D003937:Diagnosis, Differential; D004452:Echocardiography; D004562:Electrocardiography; D004699:Endocardium / Q000473:pathology; D057487:Enzyme Therapy; D000795:Fabry Disease / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality / Q000473:pathology; D005260:Female; D005690:Galactose / Q000008:administration & dosage / Q000627:therapeutic use; D006331:Heart Diseases / Q000175:diagnosis / Q000209:etiology*; D006333:Heart Failure / Q000209:etiology; D006349:Heart Valve Diseases / Q000209:etiology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000209:etiology; D015994:Incidence; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D007527:Isoenzymes / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008945:Mitral Valve Prolapse / Q000209:etiology; D009206:Myocardium / Q000473:pathology; D012737:Sex Factors; D012907:Smoking; D000519:alpha-Galactosidase / Q000097:blood / Q000627:therapeutic use
D007527:Isoenzymes; D000519:alpha-Galactosidase; C459420:agalsidase beta; D005690:Galactose