The liver BCKDC activity in classic type children is often lower than 2% in healthy children, manifested as ketoacidosis, neurologic damage and mental retardation 2. The classic type is the most common and severe type in the neonatal period, accounting for 75% affected infants. According to the phenotype, MSUD can be divided into 5 types 1: classic, intermediate, intermittent, thiamine-responsive and dihydrolipoylamide dehydrogenase (E3) deficiency. Without timely intervention, the disease progresses rapidly, and the mortality and disability rate are very high. Common clinical manifestations of MSUD are feeding difficulties, epilepsy, mental retardation, ketonuria and maple-like body odor. Maple syrup urine disease (MSUD, OMIM # 248600) is a hereditary branched-chain amino acid metabolism disorder caused by branched chain α-ketoacid dehydrogenase multi-enzyme complex (BCKDC). Computational structural modeling indicated that these novel variations probably affect structural stability and considered as likely pathogenic variants. NGS plus Sanger sequencing detection is effective and accurate for gene diagnosis. In addition, 4 previously unidentified variants (p.Gly281Arg in BCKDHA gene, p.Ser171Pro, p.Gly95Ala and p.Lys222Thr in BCKDHB gene) were identified. Totally, 13 variants were detected, including 2 variants (p.Ala216Val and p.Gly281Arg) in BCKDHA gene, 10 variants (p.Gly95Ala, p.Ser171Pro, p.Phe175Leu, p.Arg183Trp, p.Lys222Thr, p.Arg285Ter, p.Arg111Ter, p.S184Pfs*46, p.Arg170Cys, p.I160Ffs*25) in BCKDHB gene, 1 variant (p.Arg431Ter) in DBT gene. Targeted NGS revealed 2 pedigrees with MSUD Ia, 5 pedigrees with Ib, 1 pedigree with MSUD II. All the coding regions and exon/intron boundaries of BCKDHA, BCDKHB, DBT and DLD genes were analyzed by targeted NGS in the 8 MSUD pedigrees. In this report, 8 patients (4 females and 4 males) with MSUD from 8 unrelated Chinese Han families were diagnosed at the age of 6 days to 4 months. Only a few cases of MSUD have been documented in Mainland China. Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder that affects the degradation of branched chain amino acids (BCAAs).
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