title: [Clinical and mutational study of a Chinese infant with isovaleric acidemia].
abstract: OBJECTIVE
  Isovaleric acidemia (IVA) is an autosomal recessive inborn error of leucine metabolism caused by a deficiency of the mitochondrial enzyme isovaleryl-CoA dehydrogenase (IVD) resulting in the accumulation of derivatives of isovaleryl-CoA. IVA is considered to be a severe, potentially life-threatening disorder that manifests with acute neonatal encephalopathy in approximately half of affected individuals, and recurrent episodes of vomiting, lethargy, coma and varying degrees of developmental delay in the other half of patients. This study was conducted to investigate the clinical features and IVD gene mutations of a Chinese patient with IVA.
  
  
  METHODS
  The clinical features, routine laboratory data, blood amino acid and acylcarnitine profiles and urinary organic acid profiles of a patient with IVA were reviewed. Whole coding exons of IVD gene were PCR-amplified for DNA sequencing. The novel mutation c.466G > C (G127A) was confirmed by RFLP with restriction endonuclease Hph I.
  
  
  RESULTS
  The patient was a 2 year and 7 month-old boy. At 3 days of age, he began to show severe vomiting and acidosis. He was treated with pyloromyotomy at 10 days of age. His recurrent vomiting was not ameliorated until beginning transition to a diet that included more carbohydrate from 4 months. He had 3 recurrent severe vomiting and acidosis later and showed obvious psychomotor retardation. Blood spot acylcarnitine profiles by MS-MS demonstrated an elevation of C5-carnitine with a peak concentration of 12.89 micromol/L (< 0.5 micromol/L). Organic acid analysis of urine by GC-MS revealed a relatively high level of isovaleric glycine. Mutational analysis of the patient's IVD gene revealed heteroallelic mutations of c.149G > A (R21H) and c.466G > C (G127A) which is a novel missense mutation. G127A mutation was not detected in any of 50 normal controls.
  
  
  CONCLUSIONS
  From the clinical course, obvious elevation of blood C5-carnitine and urine isovaleric glycine, this patient's disorder should be classified as "metabolically severe" type of IVA which suggest that c.466G > C (G127A) mutation could severely damage the function of the IVD protein. To our knowledge, this is the first characterization of IVD gene mutations in the mainland of China.
authors.affiliation: Department of Pediatric Endocrinology, Genetics and Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Wen-juan
authors.initials: WJ
authors.lastname: Qiu
authors.forename: Xue-fan
authors.initials: XF
authors.lastname: Gu
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
authors.forename: Lian-shu
authors.initials: LS
authors.lastname: Han
authors.forename: Hai-tao
authors.initials: HT
authors.lastname: Bai
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Xiao-lan
authors.initials: XL
authors.lastname: Gao
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Hui-wen
authors.initials: HW
authors.lastname: Zhang
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D050769:Isovaleryl-CoA Dehydrogenase / Q000235:genetics*; D008297:Male; D009154:Mutation; D053719:Tandem Mass Spectrometry
chemical_list: D050769:Isovaleryl-CoA Dehydrogenase