Molecular Genetics and Metabolism

Texto completo. Acesso restrito. p. 60Mucopolysaccharidosis VI (MPS VI) is caused by deficiency of N-acetylgalactosamine 4-sulfatase (ARSB) resulting in storage of dermatan-sulphate in lysosomes and leading to progressive and severe bone dysplasia and to problems in many organs and systems. MPS VI is a very rare condition, which has a relatively high incidence in the county of Monte Santo, in Northeast Brazil (50,000 inhabitants, with 13 MPS VI cases identified thus far). A common mutation (H178L) was identified in all cases. As MPS VI can be treated with ERT and as there are indications that a better outcome may be expected in early treated cases, a newborn screening program for MPS VI was added to the program already in place for PKU, hypothyroidism and hemoglobin disorders, including ARSB assay and detection of the common mutation on DBS. The project started in January, 2011 and a total of 1,000 samples were analyzed through June, 2012. During this period, 55 samples showed ARSB enzyme activity below normal reference values, and 19 of them presented the specific mutation in heterozygosity. With these results we conclude that the methodology developed for MPS VI newborn screening is effective for early detection of the disease in the studied region. The frequency of heterozygotes found for the population of Monte Santo was considered significant, taking into account the disease rarity. The program is in progress, as an increased sample size will allow us to estimate more precisely the frequency of the mutation and the expected number of heterozygotes and homozygotes in the region, which will be important for a population medical genetics approach to the community, including genetic counseling, prenatal, diagnosis and early treatment