Screening for Fabry disease in left ventricular hypertrophy: documentation of a novel mutation.
BACKGROUND
Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy.


OBJECTIVE
To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy.


METHODS
The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m2 for women or ≥ 116 g/m2 for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased.


RESULTS
A total of 47 patients with a mean left ventricular mass index of 141.1 g/m2 (± 28.5; 99.2 to 228.5 g/m2] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test - [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation.


CONCLUSIONS
In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5).
Unidade de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, PT.
Ana
A
Baptista
Unidade de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, PT.
Pedro
P
Magalhães
Unidade de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, PT.
Sílvia
S
Leão
Unidade de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, PT.
Sofia
S
Carvalho
Unidade de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, PT.
Pedro
P
Mateus
Unidade de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, PT.
Ilídio
I
Moreira
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D059788:Dried Blood Spot Testing; D000795:Fabry Disease / Q000201:enzymology* / Q000453:epidemiology*; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011174:Portugal / Q000453:epidemiology; D015995:Prevalence; D000519:alpha-Galactosidase / Q000097:blood / Q000235:genetics*
D000519:alpha-Galactosidase