Abstract
Background
Fabry 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.
Methods
We 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.
Results
In 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.
Conclusions
These 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.
Keywords
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Article info
Publication history
Published online: September 21, 2017
Footnotes
Funding: This study was supported, in part, by a grant from Sanofi Genzyme.
Conflict of Interest: None.
Authorship: All authors had access to the data and a role in writing the manuscript.
Identification
Copyright
© 2018 Elsevier Inc. All rights reserved.
