title: Five novel mutations in ARG1 gene in Chinese patients of argininemia.
abstract: BACKGROUND
  Argininemia is an autosomal recessive genetic disorder caused by hepatocyte arginase deficiency. It could be detected by blood amino acids analysis (high arginine) and confirmed by molecular diagnosis. The clinical manifestations in patients are similar to cerebral palsy so the diagnosis is usually much delayed. Reports of argininemia from mainland China are few, and genetic analyses have not been reported.
  
  
  METHODS
  Five Chinese patients with argininemia were investigated. They had progressive spastic tetraplegia, poor physical growth from 1 month to 4 years. When argininemia was found at the ages of 4 to 12 years, four of patients had mental retardation, and three had seizures.
  
  
  RESULTS
  Elevated blood arginine and significantly decreased erythrocyte arginase activity in five patients confirmed the diagnosis of arginase deficiency. Liver dysfunction was found in four patients, two of whom had mildly elevated blood ammonia levels. Cranial magnetic resonance imaging showed progressive cerebral atrophy in three patients. Six mutations in the ARG1 gene were identified, of which only one (c.703 G>A, p.G235R) in exon 7 has been reported before; c.34 G>T (p.G12X) in exon 1, c.67delG (p.G23fsX31) in exon 2, c.539G>C (p.R180 T) in exon 5, c.374C>T (p.A125 V) in exon 4, and c.646-649del CTCA (p.T215fsX219) in exon 6 were novel mutations.
  
  
  CONCLUSIONS
  Argininemia is one of the few treatable causes of pediatric spastic paraparesis. Early metabolic investigation is very important to reach a diagnosis and better outcome. Five Chinese patients with late-diagnosed argininemia were reported. The mutation spectrum of ARG1 gene should be different from other populations.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Tong-Fei
authors.initials: TF
authors.lastname: Wu
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Liu
authors.forename: Xi-Yuan
authors.initials: XY
authors.lastname: Li
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ding
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Ma
authors.forename: Jin-Qing
authors.initials: JQ
authors.lastname: Song
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Yang
mesh_terms: D000596:Amino Acids / Q000097:blood; D001119:Arginase / Q000097:blood / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D020162:Hyperargininemia / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*
chemical_list: D000596:Amino Acids; C116917:acylcarnitine; C574619:ARG1 protein, human; D001119:Arginase; D002331:Carnitine