Fabry disease in patients under dialysis: A screening study and identification of a novel mutation

• Autor(a) principal: Silva, Francisca Gomes
• Data de Publicação: 2021
• Outros Autores: Pestana, Nicole, Durães, José, Silva, Gil
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.26/38780
• topic: Genetic Screening; X‑Linked genetic screening; Chronic Renal Failure; End‑Stage renal Kidney Disease; Hereditary Ventricular Hypertrophy; Madeira Island; Região Autonoma da Madeira; Portugal

Fabry disease (FD) is a rare systemic disease, with a large spectrum of disease severity. A GLA gene mutation in X‑chromosome leads to progressive accumulation of globotriaosylceramide (Gb3) in various organs. We screened all patients under dialysis from a single center for GLA gene changes. Enzymatic activity of alpha galactosidase A (α‑Gal A) and concentration of lyso‑Gb3 were determined in dried blood spots. Genetic study was performed in male patients with low α‑Gal A activity and in all female subjects. For all positive patients, a complete family study was performed. A total of 72 dialysis patients were screened. Sequence analysis was carried out in 53 patients (25 males). Heterozygous variants of the GLA gene were found in 4 patients (7.5%): c.937G>T (D313Y) in exon 6; c.352C>T (R118C) in exon 2; c.870G>C (M290I) in exon 6 and c.580A>G (T194A) in exon 4. Family screening was performed in a total of 17 subjects, with a GLA genetic variant prevalence of 58.8%. Unlike p.D313Y and p.R118C, well‑known non‑pathogenic polymorphisms, p.M290I is a controversial poorly described mutation. Reports about its phenotypic expression are crucial for a better understanding of its behavior. The recognition of the novel mutation p.T194A is importante for better knowledge of FD and its spectrum of clinical manifestations. These affected patients are expected to develop a classic and life‑threatening FD phenotype and an early diagnosis is essential for their treatment success.