GLA Gene Mutation in Hypertrophic Cardiomyopathy with a New Variant Description: Is it Fabry's Disease? / Mutação do Gene GLA na Cardiomiopatia Hipertrófica com Descrição de Nova Variante: É Doença de Fabry?
Chaves-Markman, Ândrea Virgínia; Markman, Manuel; Calado, Eveline Barros; Pires, Ricardo Flores; Santos-Veloso, Marcelo Antônio Oliveira; Pereira, Catarina Maria Fonseca; Lordsleem, Andréa Bezerra de Melo da Silveira; Lima, Sandro Gonçalves de; Markman Filho, Brivaldo; Oliveira, Dinaldo Cavalcanti de.
Arq. bras. cardiol
; 113(1): 77-84, July 2019. tab, graf
Artículo
en Inglés
| LILACS | ID: biblio-1011241
Abstract
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.
Biblioteca responsable:
BR1.1
Texto completo
Documentos relacionados