Fabry disease is a rare genetic lysosomal storage disease, inherited in an X-linked manner, characterized by lysosomal deposition of globotriaosylceramide due to deficient activity of the enzyme α-galactosidase A. Because the prevalence of this genetic disorder is unknown in the Emilia Romagna region, we conducted a screening study to assess the prevalence of Fabry disease in the city of Modena, Italy.
Material and Methods
A screening study has been conducted in patients on renal replacement therapy at University Hospital of Modena. Screening tests have been performed using dried blood spot method. Alpha-galactosidase A activity and Lyso-Gb3 levels were evaluated in peripheral blood of all men. In women test based on genetic analysis; Lyso-Gb3 was measured only in patients with mutation of gene GLA.
Screening tests have been performed on 388 subjects: 181 maintenance hemodialysis patients, 166 kidney transplant recipients and 41 peritoneal dialysis patients. About 40% of the patients did not had etiological diagnosis of renal disease. Lyso-Gb3 was more specific test than α- galactosidase A (100% vs. 82.5%) to diagnose Fabry disease. We found two different mutations: c.13 A>G p.(Asn5Asp), a variant likely benign and c.937 G>T p.(Asp313Tyr) a variant of uncertain significance. Both the patients carrying these genetic mutations had no symptoms or medical history compatible with Fabry disease.
Identification of variant of uncertain significance such as c.937G>Tp.(Asp313Tyr) showed the limits of genetic analysis to diagnose an inherit disease. Further studies are need to assess the diagnostic value of Lyso-Gb3 for screening for Fabry disease.
KEYWORDS: Fabry Disease, Screening; Lyso-Gb3; c.13 A>G p. Asn5Asp; c.937 G>T p.(Asp313Tyr); D313Y; α-galactosidase A