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Volume 113, Nº 1, July 2019


DOI: http://www.dx.doi.org/10.5935/abc.20190112


GLA Gene Mutation in Hypertrophic Cardiomyopathy with a New Variant Description: Is it Fabry's Disease?

Ândrea Virgínia Chaves-Markman

Manuel Markman

Eveline Barros Calado

Ricardo Flores Pires

Marcelo Antônio Oliveira Santos-Veloso

Catarina Maria Fonseca Pereira

Andréa Bezerra de Melo da Silveira Lordsleem

Sandro Gonçalves de Lima

Brivaldo Markman Filho

Dinaldo Cavalcanti de Oliveira

Figure 1 – Chromatogram of the novel GLA gene mutation: c.967C>A (p.Pro323Thr).


Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the alpha galactosidase A gene (GLA) that lead to the enzymatic deficiency of alpha galactosidase (α-Gal A), resulting in the accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3), causing multiple organ dysfunctions.

Objective: To perform GLA gene screening in a group of patients with echocardiographic diagnosis of hypertrophic cardiomyopathy (HCM).

Methods: A cross-sectional study was conducted with HCM patients from a university hospital. Patients with coronary artery disease and valvulopathies were excluded. Mutation analysis of the GLA gene was performed. In male subjects, the analysis was performed after evidence of low α-Gal A activity.

Results: 60 patients with echocardiographic diagnosis of HCM were included. Age ranged from 12 to 85 years and 60% were women. Mean myocardial fibrosis percentage on MRI was 10.7 ± 13.1% and mean ventricular thickness was18.7 ± 6.7 mm. Four patients had the following GLA gene mutations: c.967C>A (p.Pro323Thr), not yet described in the literature; c.937G>T (p.Asp313Tyr); and c.352C>T (p.Arg118Cys). All patients had normal levels of lyso-Gb3 and non-ischemic myocardial fibrosis on magnetic resonance imaging; one patient had proteinuria and one patient had ventricular tachycardia.

Conclusion: In this study, the frequency of mutation in the GLA gene in patients with HCM was 6.7%. A novel mutation in exon 6 of the GLA gene, c.967C>A (p.Pro323Thr), was identified. Patients with HCM may have GLA mutations and FD should be ruled out. Plasma (lyso-Gb3) levels do not seem to be sufficient to attain a diagnosis and organ biopsy should be considered. (Arq Bras Cardiol. 2019; 113(1):77-84)

Keywords: Fabry Disease/genetic; Cardiomyopathy, Hypertrophic; Hypertrophy, Left Ventricular; Glycosphingolipids.