Background: Maple syrup urine disease (MSUD) is caused by decreased activity of the branched-chain alpha-ketoacid dehydrogenase complex (BCKAD), the second enzymatic step in the degradative pathway of the branched-chain amino acids (BCAAs). Mutations in any of the three different genes BCKDHA, BCKDHB, and DBT encoding for the E1alpha, E1beta, and E2 catalytic components of the BCKAD complex can cause MSUD. The disease presents heterogeneous clinical and molecular phenotypes. Severity of the disease ranges from the classical to the mildest variant types. Objective: The aims of the study is to describe the phenotype and to identify mutations of BCKDHA, BCKDHB and DBT in a cohort of 18 Vietnamese patients with MSUD. Methods: this is a case series study. Clinical manifestations, biochemistry were evaluated at Vietnam National Hospital of Pediatrics (NHP) in Hanoi, Vietnam. Tandem mass spectrometry (MS/MS)-based amino acid profiling of dried blood spots and analysis of urine organic acids by gas chromatography-mass spectrometry were performed at Shimane University - Japan. Mutation analysis of BCKDHA, BCKDHB, and DBT were perfomed for 7 cases using PCR and direct sequencing. Results: 18 cases from 16 unrelated families included 10 boys and 8 girls. Age of onset was from 2 days to 15 days of age for 16 case with classic type and 4 to 6 months of age for intermediate type. 10/16 proband had family history. Clinical manifestations at initial hospitalization were maple syrup odor In cerumen (15/18); poor feeding (12/18), lethargy/iritability (15/18), coma (2/18), focal dystonia (8/18), oplsthotonus (4/18), full fontanel (3/18), central respiratory failure (9/18) in the neonatal period. Two cases with intermediate had mental retardation and maple syrup odor in cerumen at the initial hospitalization. Biochemistry changes were hyponatremla, metabolic acidosis, increased plasma concentrations of leucine and large quantity branched-chain ketoacids of leucine and isoleucine in the urine. 5 patients have only one identified mutant allele in BCKDHA (c.868GA; p.Gly290Arg, and c.1211AG; p.Asn404Ser), BCKDHB (c. 1159CT; p.Arg387X and c.1159C T; p.Arg387X), or DBT (c.263_265deIAAG; p.Glu88del) while only 2 cases are homozygous for either BCKDHA (novel mutation c.1280_1282defTGG; p.Leu427 _Ala428delinsPro) or BCKDHB (c.564TA; p.Cys188X). Conclusions: The results of this study indicate heterogeneous clinical and molecular phenotypes in Vietnamses patients with MSUD.
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