• Martin S Maron, Winnie Xin, Katherine B Sims, Rita Butler, Tammy S Haas, Ethan J Rowin, Robert J Desnick, and Barry J Maron.
• Hypertrophic Cardiomyopathy Institute, Division of Cardiology, Tufts Medical Center, Boston, Mass. Electronic address: mmaron@tuftsmedicalcenter.org.
• Am. J. Med. 2018 Feb 1; 131 (2): 200.e1-200.e8.

BackgroundFabry disease is an X-linked lysosomal storage disorder caused by the deficient activity of α-galactosidase A due to mutations in the GLA gene, which may be associated with increased left ventricular wall thickness and mimic the morphologic features of hypertrophic cardiomyopathy. Management strategies for these 2 diseases diverge, with Fabry disease-specific treatment utilizing recombinant α-galactosidase A enzyme replacement therapy.MethodsWe studied a prospectively assembled consecutive cohort of 585 patients (71% male) from 2 hypertrophic cardiomyopathy tertiary referral centers by screening for low α-galactosidase A activity in dried blood spots. Male patients with low α-galactosidase A activity levels and all females were tested for mutations in the GLA gene.ResultsIn 585 patients previously diagnosed with hypertrophic cardiomyopathy, we identified 2 unrelated patients (0.34%), both with the GLA mutation encoding P.N215S, the most common mutation causing later-onset Fabry disease phenotype. These patients were both asymptomatic, a man aged 53 years and a woman aged 69 years, and demonstrated a mild cardiac phenotype with symmetric distribution of left ventricular hypertrophy. After family screening, a total of 27 new Fabry disease patients aged 2-81 years were identified in the 2 families, including 12 individuals who are now receiving enzyme replacement therapy.ConclusionsThese observations support consideration for routine prospective screening for Fabry disease in all patients without a definitive etiology for left ventriclar hypertrophy. This strategy would likely result, through cascade family testing, in the earlier identification of new Fabry disease-affected males and female heterozygotes who may benefit from monitoring and/or enzyme replacement therapy.Copyright © 2018 Elsevier Inc. All rights reserved.

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