A953

JACC March 17, 2015

Volume 65, Issue 10S

Heart Failure and Cardiomyopathies

Prevalence of Clinically Apparent Hypertrophic Cardiomyopathy in 32 Patients with
the GLA A143T Mutation: Implications for Genetic Screening for Fabry Disease in
Patients with Hypertrophic Cardiomyopathy
Poster Contributions
Poster Hall B1
Sunday, March 15, 2015, 9:45 a.m.-10:30 a.m.

Session Title: World of Cardiomyopathies

Abstract Category: 14.  Heart Failure and Cardiomyopathies: Clinical
Presentation Number: 1184-229

Authors: Christopher Cook, Eric Farber-Eger, Thomas Wang, Quinn Wells, Vanderbilt University, Nashville, TN, USA
Background: Fabry disease is a lysosomal storage disorder caused by mutations in the GLA gene that classically presents with
multisystem involvement. One specific mutation, GLA A143T, has been proposed to cause a “cardiac variant” of Fabry disease which
presents with isolated cardiac manifestations resembling hypertrophic cardiomyopathy (HCM). However, the pathogenicity of this mutation
has been questioned and its contribution to the HCM phenotype has not been firmly established.
Methods: Using BioVU, a Vanderbilt University biorepository that links DNA to a de-identified electronic medical record, we identified
30,181 subjects who had been genotyped with the Illumina Infinium Exome Chip, which included the GLA A143T variant. Carriers of
this mutation were identified and a chart review was performed to determine the prevalence of clinically apparent HCM, defined as an
echocardiographic diagnosis of left ventricular hypertrophy (LVH) in the absence of an identified cause.
Results: Of the 30,181 DNA samples genotyped, 32 adult carriers of the GLA A143T mutation were identified. Carriers were 69% female,
94% white, and the median age was 68 (interquartile age range 58-77). No carriers had a diagnosis of Fabry disease. Echocardiography
had been performed on 14 of 32 carriers. Nine carriers were diagnosed with LVH, but all of these patients had hypertension. Two patients
had heart failure; one patient was a 91 year old male with ischemic cardiomyopathy and the other patient was a 79 year old male
diagnosed with non-ischemic cardiomyopathy in the setting of hypertension. None of the 18 carriers who did not undergo echocardiography
had a diagnosis of heart disease beyond hypertension.
Conclusion: The prevalence of clinically apparent HCM among carriers of the GLA A143T mutation was low in this study population. This
may be due to a lack of pathogenicity of the mutation, low penetrance, or the presence of only subclinical manifestations. Though this
study is limited by reliance on clinically obtained data with potential underestimation of disease burden, caution should be applied before
attributing HCM to this mutation when it is identified in screening studies.