Fabry disease / complications

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Editorial

Zebras Exist, Too!

Fabry disease (FD) is a rare X-linked hereditary lysosomal storage disease caused by deficient activity of the enzyme alpha-galactosidase A that leads to the accumulation of globotriasylceramide (Gb3) in affected tissues, including the heart, brain, and kidneys. In FD, cardiac damage begins early and progresses subclinically before the appearance of symptoms and generally manifests as left ventricular hypertrophy simulating hypertrophic cardiomyopathy (HCM). Recent studies have demonstrated a prevalence of FD of up to 5% in patients whose initial diagnosis was HCM. After the introduction of enzyme replacement therapy, FD deserves special attention in the differential diagnosis in patients with unexplained ventricular hypertrophy and HCM, as it is a heart disease that requires specific treatment. However, early diagnosis and treatment are essential to prevent the progression of the disease by reducing cardiovascular event rates.^–

With the aim of investigating the clinical and exam differences between HCM and DF, the study of Akhan et al. retrospectively evaluated 60 patients with HCM and 40 with FD. In this population, with a similar average age, the authors showed, in general, that the characteristics of the two cardiac conditions share more similarities than differences, making diagnosis a challenge in clinical practice.

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Original Article

Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

Ana Baptista et al. Pedro Magalhães Sílvia Leão Sofia Carvalho … Pedro Mateus Ilídio Moreira

Abstract

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.

Conclusion:

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).