maple syrup urine disease punnett square

Maple syrup urine disease (MSUD) (OMIM #24860), also known as leucinosis, is an inborn error of metabolism (IEM) caused by the deficiency of thiamine-dependent branched-chain α-ketoacid dehydrogenase (BCKD), composed of the subunits E1α, E1β, E2, and E3. Given that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity. Seventeen pathogenic variants were previously described and five variants showed no pathogenicity according to in silico analysis. ResultsĮight new variants predicted as pathogenic were found between 30 variants (damaging and non-damaging) identified in the 21 patients analyzed: one in the BCKDHA gene (p.Tyr120Ter) five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs * 13, p.Phe149Cysfs * 9, p.Cys207Phe, and p.Lys211Asn) and two in the DBT gene (p.Glu148Ter and p.Glu417Val). It is a descriptive cross-sectional study with 21 MSUD patients involving molecular genotyping by Sanger sequencing. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA, BCKDHB, and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. MSUD is predominantly caused by Variants in BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1β, and E2 subunits of BCKD complex, respectively.

BCKD is a mitochondrial complex encoded by BCKDHA, BCKDHB, DBT, and DLD genes. Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. Orphanet Journal of Rare Diseases volume 15, Article number: 309 ( 2020) Maple syrup urine disease in Brazilian patients: variants and clinical phenotype heterogeneity

Maple syrup urine disease punnett square