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Previous Volume 333:288-293 August 3, 1995 Number 5 Next

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ABSTRACT

Background fabry's disease is an x-linked recessive disorder that results from a deficiency of -galactosidase. Left ventricular hypertrophy is one of the common manifestations in men with classic hemizygous disease. Recently, several cases of an atypical variant of hemizygous Fabry's disease, with manifestations limited to the heart, have been reported. Therefore, we assessed the incidence of hemizygosity for Fabry's disease among male patients with left ventricular hypertrophy.

Methods We measured plasma -galactosidase activity in 230 consecutive male patients with left ventricular hypertrophy. Clinical manifestations were assessed, endomyocardial biopsies were performed, and the patients were screened for mutations in the -galactosidase gene.

Results Seven of the 230 patients with left ventricular hypertrophy (3 percent) had low plasma -galactosidase activity (4 to 14 percent of the mean value in normal controls). These seven unrelated patients, ranging in age from 55 to 72 years, did not have angiokeratoma, acroparesthesias, hypohidrosis, or corneal opacities, which are typical manifestations of Fabry's disease. Endomyocardial biopsy was performed in five patients and revealed marked sarcoplasmic vacuolization in all five. samples from four patients were examined by electron microscopy and revealed typical lysosomal inclusions with a concentric lamellar configuration in all four. Two patients had novel missense mutations in exon 1 and exon 6. The remaining five had no mutations in the coding region of the -galactosidase gene, but the amounts of the -galactosidase messenger RNA were markedly lower than normal.

Conclusions Seven unrelated patients with atypical variants of hemizygous Fabry's disease were found among 230 men with left ventricular hypertrophy. Fabry's disease should be considered as a cause of unexplained left ventricular hypertrophy.

Source Information

From the First Department of Internal Medicine (S.N., T.T., M.M., C.K., A.T., M.T., H.T.), the First Department of Pathology (A.Y.), and the Third Department of Internal Medicine (M.K.), Faculty of Medicine, Kagoshima University, Kagoshima, Japan; and the Department of Clinical Genetics, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan (H.H., H.S.).

Address reprint requests to Dr. Hiromitsu Tanaka at the First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890, Japan.

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