MUTATION TYPES AND ENZYME LEVELS IN FABRY DISEASE IN A MULTICENTER STUDY

Abstract Background and Aims Fabry disease is a chronic, progressive and multi-systemic hereditary condition, related to a Xq22 mutation in X chromosome, which results in deficiency of acid alpha-galactosidase, hence reduced capacity of globotriaosylceramide (Gb3) degradation. Gb3 accumulates in lysosomes throughout virtually every organ, thus causing considerable morbidity and mortality. Objectives: To evaluate the types of Fabry disease mutations and enzyme levels of Alpha Galactosidase and Lyso Gb3 in a multicenter study; the RIM FABRY BRASIL PROJECT. Method We conducted a transversal study that consists of data analysis secondary to the multicenter project: Clinical and Epidemiological Analysis of Fabry's Disease in Dialysis Centers in Brazil, “PROJETO RIM FABRY BRASIL”. Included 854 dialysis centers throughout Brazil and 75059 individuals screened using a questionnaire and signing an Informed Consent Form. The data were entered into a computer program (algorithm) that filters the possible carriers of Fabry's disease. The program / algorithm discarded those who probably did not have Fabry's disease and sent blood suspects to filter enzyme dosage and genetic testing of those suspected of the disease. Results 75059 individuals from the RIM FABRY BRASIL project were screened, where 58.37% were men and 41.54% women. 408 individuals with mutations for Fabry disease were identified, including patients with kidney and Family history of the disease, 34.6% men and 65.4% women with a mean age of 42.7 years. 47 different mutations were identified, with a higher prevalence of c.352C> T p.Arg118Cys (24.8%), followed by c.376A> G p.Ser126Gly (13.1%), c.1102G> A p.Ala368Thr ( 7.8%), c.937G> T p.Asp313Tyr (7.8%), c.870G> C p.Met290Ile (7.3%). Alfa GalA dosage was performed in 120 men, with 90% of them showing decreased enzyme and Lyso Gb3 dosage of 320 individuals, (36.2% men and 63.8% women) 72.5% normal and 27.5% increased. Conclusion The most frequent mutations were: c.352C> T p.Arg118Cys, followed by c.376A> G p.Ser126Gly, c.1102G> A p.Ala368Thr, c.937G> T p.Asp313Tyr, c.870G> C p.Met290Ile. 90% of men showed a decrease in the enzyme Alpha GalA and 27.5% of individuals had increased Lyso Gb3.