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Fabry disease
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  1. S F Nagueh
  1. Correspondence to:
    Sherif F Nagueh, MD, Section of Cardiology, 6550 Fannin Street, SM-1246, Houston, TX 77030-2717, USA;
    sherifn{at}bcm.tmc.edu

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It is incumbent upon physicians evaluating men with unexplained left ventricular hypertrophy—particularly those without severe outflow tract obstruction—to consider Fabry disease in the differential diagnosis

Fabry disease is a rare X linked recessive disorder resulting from a deficiency of the lysosomal enzyme α galactosidase A. Accordingly, hemizygous males have the most severe form of the disease and heterozygous females usually have a more benign presentation.1 The enzymatic defect in this lysosomal storage disease leads to the accumulation of globotriaosylceramide in several organs including the skin, kidney, nervous system, cornea, and the heart. Patients with the classic form suffer from acroparesthesias, hypohidrosis, angiokeratomas, corneal opacities, cerebrovascular lesions, cardiac disorders, and renal dysfunction. More than 160 mutations in the α galactosidase A gene have been reported. Depending on the mutation, the enzyme activity may be reduced or abolished. In the more benign mutations, the enzyme activity and stability are reduced but the active site is still capable of binding to the substrate. These mutant forms of the protein may be stabilised by chemical chaperones such as galactose that bind to the active site of the enzyme.2,3 This in turn promotes some folding and stability of the protein until it is transported into the lysosomes. There, the accumulated globotriaosylceramide molecules displace the chaperone and are hydrolysed by the enzyme. Therefore in selected patients where the enzyme active site is still capable of binding to the substrate, galactose can be used to increase the enzyme activity and decrease the accumulation of the globotriaosylceramide molecules.3

CARDIAC MANIFESTATIONS OF FABRY DISEASE

There are two forms of cardiac disease: one where the heart is affected along with other organs; and …

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