title: Eleven novel mutations of the BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease in the Chinese population: Report on eight cases.
abstract: Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder that affects the degradation of branched chain amino acids (BCAAs). Only a few cases of MSUD have been documented in Mainland China, and prenatal diagnosis has not been performed so far. In this report, 8 patients (4 girls and 4 boys) with MSUD from 8 unrelated Chinese families were diagnosed at the age of 9 days to 1 year and 8 months. The diagnosis was confirmed by serum BCAAs and genetic analyses. Among the 8 patients, only one was detected by newborn screening. The remaining 7 patients were admitted because of neurological disorders and underwent selective screening. Significantly elevated BCAAs were observed in 7 patients. One patient was diagnosed by post-mortem study. 12 mutations were found in the BCKDHA, BCKDHB and DBT genes. 11 of these mutations were novel: c.178G > T, c.491T > C, c.740A > G, c.1214_1219dupCCAACC and IVS6+1delG in BCKDHA; c.482T > G, c.508C > T, c.767A > G, c.768C > G and IVS4,-2A > C in BCKDHB; and c.1A > G in DBT. Only one mutation, c.659C > T in the BCKDHA gene, had been previously reported. 7 patients were treated by dietary intervention and symptomatic therapy. 6 of them showed clinical improvement. The mother of one patient who died from MSUD underwent amniocentesis during her second pregnancy. The BCAAs level in her amniotic fluid was normal. Only one heterozygous mutation, IVS4,-2A > C in the BCKDHB gene, was detected in the cultured amniocytes. The results revealed that the fetus was not affected by MSUD. Normal development and the blood BCAAs profile confirmed the prenatal diagnosis after birth. Thus, we identified eleven novel mutations associated with MSUD in the Chinese population. Prenatal diagnosis of MSUD was successfully performed on one fetus by genetic analysis of the cultured amniocytes.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Xiyuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Jinqing
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Similan Clinic, Beijing 100070, China.
authors.forename: Mengqiu
authors.initials: M
authors.lastname: Li
authors.affiliation: Similan Clinic, Beijing 100070, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. Electronic address: yanlingy@vip.sina.com.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008375:Maple Syrup Urine Disease / Q000175:diagnosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation
keywords: BCKDHA gene; BCKDHB gene; Branched chain amino acids; DBT gene; Maple syrup urine disease; Prenatal diagnosis