RESUMO
BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by the deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by four genes: BCKDHA, BCKDHB, DBT, and DLD. MSUD is predominantly caused by mutations in the BCKDHA, BCKDHB, and DBT genes which encode the E1α, E1ß, and E2 subunits of the BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD in a cohort of Chilean MSUD patients by identifying point mutations in the BCKDHA, BCKDHB, and DBT genes and to describe their impact on the phenotypic heterogeneity of these patients. METHODS: This manuscript describes a cross-sectional study of 18 MSUD patients carried out using PCR and DNA sequencing. RESULTS: Four novel pathogenic mutations were identified: one in BCKDHA (p.Thr338Ile), two in BCKDHB (p.Gly336Ser e p.Pro240Thr), and one in DBT (p.Gly406Asp). Four additional pathogenic mutations found in this study have been described previously. There were no correlations between the genotype and phenotype of the patients. CONCLUSION: If MSUD is diagnosed earlier, with a newborn screening approach, it might be possible to establish genotype-phenotype relationships more efficiently.
Assuntos
Doença da Urina de Xarope de Bordo/genética , Mutação , 3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/genética , Aciltransferases/genética , Criança , Chile , Di-Hidrolipoamida Desidrogenase/genética , Testes Genéticos/estatística & dados numéricos , Humanos , Doença da Urina de Xarope de Bordo/patologiaRESUMO
Foi determinado o grau de incapacidade em 189 pacientes hansenianos virgens de tratamento, sendo 39 Tuberculóides, 16 Indeterminados, 91 Dimorfos e 43 Virchowianos. Apenas 62 (32,8%) dos pacientes apresentavam grau 0, nos 127 (67,2%) restantes, os graus I, II e III determinados indicam a necessidade de educaçao sanitária e técnicas simples de fisioterapia, para evitar a instalaçao de sequelas irreversíveis
Assuntos
Avaliação da Deficiência , HanseníaseRESUMO
Foi determinado o grau de incapacidade em 189 pacientes hansenianos virgens de tratamento, sendo 39 Tuberculóides, 16 Indeterminados, 91 Dimorfos e 43 Virchowianos. Apenas 62 (32,8) dos pacientes apresentavam grau 0, nos 127 (67,2) restantes, os graus I, II e III determinados indicam a necessidade de educação sanitária e técnicas simples de fisioterapia, para evitar a instalação de sequelas irreversíveis