title: Two novel compound heterozygous mutations in the BCKDHB gene that cause the intermittent form of maple syrup urine disease.
abstract: Intermittent maple syrup urine disease (MSUD) is a potentially life-threatening metabolic disorder caused by a deficiency of branched chain α-ketoacid dehydrogenase (BCKD) complex. In contrast to classic MSUD, children with the intermittent form usually have an atypical clinical manifestation. Here, we describe the presenting symptoms and clinical course of a Chinese boy with intermittent MSUD. Mutation analysis identified two previously unreported mutations in exon 7 of the BCKDHB gene: c.767A > G (p.Y256C) and c.768C > G (p.Y256X); the parents were each heterozygous for one of these mutations. In silico analysis predicted Y256C probably affects protein structure; Y256X leads to a premature stop codon. This case demonstrates intermittent MSUD should be suspected in cases with symptoms of recurrent encephalopathy, especially ataxia or marked drowsiness, which usually present after the neonatal period and in conjunction with infection. symmetrical basal ganglia damage but normal myelination in the posterior limb will assist differential diagnosis; alloisoleucine is a useful diagnostic marker and mutation analysis may be of prognostic value. These novel mutations Y256C and Y256X result in the clinical manifestation of a variant form of MSUD, expanding the mutation spectrum of this disease.
authors.affiliation: Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China, 400014. yig0274@aliyun.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China. Liming_liu@163.com.
authors.forename: Liu
authors.initials: L
authors.lastname: Liming
authors.affiliation: Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China, 400014. dr_jiangli@126.com.|Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China. dr_jiangli@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000235:genetics*; D019943:Amino Acid Substitution; D001479:Basal Ganglia / Q000473:pathology; D001921:Brain / Q000473:pathology; D003062:Codon / Q000235:genetics; D003198:Computer Simulation; D038524:Diffusion Magnetic Resonance Imaging; D005091:Exons / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008375:Maple Syrup Urine Disease / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009186:Myelin Sheath / Q000473:pathology; D011379:Prognosis
chemical_list: D003062:Codon; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
keywords: BCKDHB gene; Maple syrup urine disease; Mutation; Variant form