Novel α-galactosidase A mutation in patients with severe cardiac manifestations of Fabry disease.

Fabry disease (FD) is a hereditary metabolic disorder caused by the partial or total inactivation of α-galactosidase A (α-gal A), a lysosomal hydrolase. This inactivation is responsible for the accumulation of undegraded glycosphingolipids in the lysosomes with subsequent cellular and microvascular dysfunction. Fabry is considered a rare disease, with an incidence of 1:40,000; however, there are good reasons to believe that it is often seen but rarely diagnosed. To date, more than 600 mutations have been identified in human GLA gene that are responsible for FD. We describe the case of a 54-year-old male patient, who presented with left ventricular hypertrophy, chronic renal failure and acroparaesthesias, which are considered to be specific features of FD. Clinical and instrumental investigations showed several cardiovascular manifestations. The molecular analysis of GLA gene revealed a novel mutation in the fifth exon, called N249K, and the enzymatic analysis showed no α-galactosidase A activity. Family screening detected the same mutation in some relatives and also the enzymatic analysis confirmed the diagnosis of FD. In conclusion, these data suggest that the N249K mutation may be associated with cardiac manifestations of FD combined with other classical features of the disease.