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(Circulation. 2004;110:1047-1053.)
© 2004 American Heart Association, Inc.

Original Articles

Prevalence of Fabry Disease in Female Patients With Late-Onset Hypertrophic Cardiomyopathy

Cristina Chimenti, MD PhD; Maurizio Pieroni, MD; Emanuela Morgante, MD; Daniela Antuzzi, PhD; Andrea Russo, MD; Matteo Antonio Russo, MD; Attilio Maseri, MD; Andrea Frustaci, MD

From the Cardio-Thoracic and Vascular Department (C.C., M.P., A.M.), San Raffaele Hospital, Milan, Italy; Pathology Department (E.M., M.A.R.), "La Sapienza" University, Rome, Italy; Pediatrics (D.A.) and Cardiology Department (A.F.), Catholic University, Rome, Italy; and Biopathology and Diagnostic Imaging Department, "Torvegata" University, and IRCC "Regina Elena" Institute (A.R.), Rome, Italy.

Reprint requests to Andrea Frustaci, MD, Cardiology Department, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy. E-mail biocard{at}rm.unicatt.it

Received September 19, 2003; de novo received January 12, 2004; revision received March 30, 2004; accepted April 2, 2004.

Background— Fabry disease (FD) has been recognized as the cause of left ventricular hypertrophy in 6% of men with late-onset hypertrophic cardiomyopathy (HCM). Although FD is considered a recessive X-linked disorder, affected women are increasingly reported. The aim of our study was to determine the prevalence of FD in female patients with HCM.

Methods and Results— Thirty-four consecutive women (mean age, 50±13.6 years) who received an ECG and echocardiographic diagnosis of HCM were submitted to an invasive cardiac study that included a biventricular endomyocardial biopsy. Tissue samples were analyzed for histology and electron microscopy. Peripheral blood activity of -galactosidase (-Gal) A was assessed in all patients. None of them had a family history of FD. Histology and electron microscopy showed in 4 patients (12%; mean age, 51.5±3.9 years) the presence of cell vacuoles characterized by the accumulation of glycolipid material organized in concentric lamellar structures, diagnostic for FD. In the remaining patients, histology was consistent with HCM. In all the female carriers, the heart was the only organ clinically involved in the disease, showing concentric hypertrophy in 2 patients, asymmetric hypertrophy in 1, and apical hypertrophy in 1. The -Gal A enzymatic activity was 44±14% of control values. Genetic analysis showed the presence of -Gal A gene mutation in all 4 cases.

Conclusions— FD may account for up to 12% of females with late-onset HCM. Those heterozygous for FD with left ventricular hypertrophy are potential candidates for enzyme enhancement/replacement therapy.

Key Words: biopsy • cardiomyopathy • hypertrophy

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