title: [Analysis of clinical features and GCDH gene mutations in four patients with glutaric academia type I].
abstract: OBJECTIVE
  To review clinical features of four male patients with glutaric academia type I and screen glutaryl-CoA dehydrogenase (GCDH) gene mutations.
  
  
  METHODS
  The 4 patients underwent brain computer tomography (CT) and magnetic resonance imaging (MRI) analyses. Blood acylcarnitine and urine organic acid were analyzed with tandem mass spectrometry and gas chromatographic mass spectrometry. Genomic DNA was extracted from peripheral blood samples. The 11 exons and flanking sequences of GCDH gene were amplified with PCR and subjected to direct DNA sequencing.
  
  
  RESULTS
  All patients have manifested macrocephaly, with head circumference measured 50 cm (14 months), 47 cm (9 months), 46 cm (5 months) and 51 cm (14 months), respectively. Imaging analyses also revealed dilation of Sylvian fissure and lateral ventricles, frontotemporal atrophy, subarachnoid space enlargement and cerebellar vermis abnormalities. All patients had elevated glutarylcarnitine (5.8 umol/L, 7.5 umol/L, 8.3 umol/L and 7.9 umol/L, respectively) and high urinary excretion of glutaric acid. Seven mutations were identified among the patients, among which c.146_149del4, IVS6-4_Ex7+4del8, c.508A>G (p.K170E), c.797T>C (p.M266T) and c.420del10 were first discovered.
  
  
  CONCLUSIONS
  Macrocephaly and neurological impairment are the most prominent features of glutaric academia type I. Blood tandem mass spectrometry and urine gas chromatographic mass spectrometry analysis can facilitate the diagnosis. The results can be confirmed by analysis of GCDH gene mutations.
authors.affiliation: Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen, Guangdong 518026, PR China.
authors.forename: Peng -qiang
authors.initials: P-
authors.lastname: Wen
authors.forename: Guo-bing
authors.initials: GB
authors.lastname: Wang
authors.forename: Xiao-hong
authors.initials: XH
authors.lastname: Liu
authors.forename: Zhan-ling
authors.initials: ZL
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Shang
authors.forename: Dong
authors.initials: D
authors.lastname: Cui
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.forename: Shu-li
authors.initials: SL
authors.lastname: Chen
authors.forename: Jian-xiang
authors.initials: JX
authors.lastname: Liao
authors.forename: Cheng-rong
authors.initials: CR
authors.lastname: Li
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D001928:Brain Diseases, Metabolic / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D050770:Glutaryl-CoA Dehydrogenase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment
chemical_list: D050770:Glutaryl-CoA Dehydrogenase