An atypical p.N215S variant of Fabry disease with end-stage renal failure

摘要

Fabry disease is an X-linked metabolic disorder resulting in widespread deposition of Globotriaosylceramide within a variety of human tissues. The classical Fabry phenotype is one of early onset disease, with extensive tissue involvement resulting in acroparaesthesia, gastrointestinal disturbances, angiokeratoma, cornea verticillata renal failure, and cardiovascular disease.We describe two brothers exhibiting the GLA p.N215S mutation, a variant most often conferring a late-onset disease confined to the myocardium.The proband was diagnosed aged 34, following investigation into proteinuria.Despite Enzyme Replacement Therapy, he progressed to end-stage renal failure, and subsequently received a renal transplant. He also developed hypertrophic cardiomyopathy.His sibling however, whose disease was detected aged 32 following screening, exhibits mild left ventricular hypertrophy, and no evidence of renal disease. He remains clinically asymptomatic.This case report details a discordant phenotype in brothers with Fabry disease and p.N215S mutation. Despite the fact that in the majority of patients this mutation is associated with a late onset presentation with hypertrophic cardiomyopathy, we have clearly demonstrated that patients with GLA p.N215S mutation can present with the classical phenotype. Further studies are required to elucidate the underlying modifying factors that influence clinical presentation with a more severe phenotype. Keywords: Fabry disease, p.N215S, Genetics, Metabolic disease