Fabry disease: focus on cardiac manifestations and molecular mechanisms.
METHODS
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.
Perrot
Andreas
A
University Hospital Charité, Cardiology at Campus Virchow-Klinikum & Campus Buch, Humboldt University Berlin, Germany.
Osterziel
Karl Josef
KJ
Beck
Michael
M
Dietz
Rainer
R
Kampmann
Christoph
C
D000293:Adolescent; D000328:Adult; D000787:Angina Pectoris / Q000209:etiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D002312:Cardiomyopathy, Hypertrophic / Q000209:etiology; D002460:Cell Line; D002648:Child; D006224:Cricetinae; D003937:Diagnosis, Differential; D004562:Electrocardiography; D000795:Fabry Disease / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D005260:Female; D005818:Genetic Engineering; D006331:Heart Diseases / Q000209:etiology*; D006349:Heart Valve Diseases / Q000209:etiology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000209:etiology; D007527:Isoenzymes / Q000627:therapeutic use; D008297:Male; D016032:Randomized Controlled Trials as Topic; D012737:Sex Factors; D013997:Time Factors; D000519:alpha-Galactosidase / Q000627:therapeutic use
D007527:Isoenzymes; D000519:alpha-Galactosidase; C459420:agalsidase beta