Abstract 917: Fabry’s Disease Mimicking Hypertrophic Cardiomyopathy (HCM)- Screening For Galactosidase (GAL) Gene Mutations in a HCM Cohort
Introduction: Hypertrophic cardiomyopathy (HCM) is caused by mutations in genes encoding cardiac sarcomere proteins. However, ECG and echocardiographic changes seen in Fabry’s disease - that is caused by mutations in the galactosidase (GAL) gene - may resemble HCM due to changes in cardiac sarcomere proteins. A differentiation is important because of therapeutic options.
Methods: A consecutive cohort of 90 HCM probands and their relatives (460 persons) was evaluated by patient and family histories, physical examinations, ECG and echocardiography. All probands were genetically screened by a combination of single strand conformation / heteroduplex analysis and direct sequencing.
Results: Among the 90 probands 33 (37%) had mutations in one or more of 9 sarcomere genes screened. Three probands had mutations in the GAL gene. One female proband (55 years of age) with pronounced asymmetric septal hypertrophy, atrial fibrillation and bi-atrial enlargement was heterozygous for the novel G239S mutation in GAL. Her serum alpha-galactosidase activity was reduced to 11 U/mg protein (reference 18–54). No other clinical findings pointed towards Fabry’s disease. Another female proband (57 years of age) with asymmetric septal hypertrophy, a significant LVOT gradient and COPD with intermittent haemoptysis was heterozygous for the novel N139T mutation in GAL. Finally, one male proband (52 years of age) with pronounced asymmetric septal hypertrophy was hemizygous for the A156T in GAL. This mutation has previously been reported. His 29 years old daughter was heterozygous for the A156T mutation. She was asymptomatic without any cardiac signs or symptoms. Her serum alpha-galactosidase activity was normal (35 U/mg protein).
Conclusions: The finding of mutations in the GAL gene in 3 of 90 patients (3%) with HCM emphasizes the importance of thorough evaluation for possible differential diagnoses in cardiac hypertrophy. However, only 1 of the 3 probands had other symptoms associated with Fabry’s disease. This - in combination with the putative reversibility of cardiac changes in Fabry’s disease by enzyme substitution with alpha-galactosidase - strongly supports the use of genetic screening.