title: Clinical and mutational spectra of 23 Chinese patients with glutaric aciduria type 1.
abstract: OBJECTIVE
  Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder caused by glutaryl-CoA dehydrogenase deficiency due to GCDH gene mutations. In this study, the clinical presentation and molecular aspects of 23 Chinese patients (11 males and 12 females) were investigated.
  
  
  METHODS
  All patients were diagnosed by elevated urinary glutaric acid and GCDH gene analysis. Protein-restricted diet supplemented with special formula, l-carnitine and GABA analog were initialed after diagnosis. The clinical and biochemical features were analyzed. Mutational analysis of GCDH was conducted.
  
  
  RESULTS
  Clinical manifestations of 23 patients varied from asymptomatic to severe encephalopathy, with notable phenotypic differences between siblings with the same mutations. One case was detected by newborn screening, while 22 Cases were diagnosed between the ages of 5 months and 51 years. 29 mutations in GCDH were identified. Among them, 11 were novel, including seven missense mutations (c.406G > T, C.416C > G, c.442G > A, c.640A > G, c.901G > A, c.979G > A, and c.1207C > T), three frameshift mutations (c.873delC, c.1172-1173insT and c.1282-1285ins71) and one nonsense mutation (c.411C > G). In exon 5, c.553G > A and c.148T > C were found in four alleles (8.7%) and three alleles (6.5%) of the patients, respectively.
  
  
  CONCLUSIONS
  In 23 Chinese patients with GA1, 11 novel GCDH mutations were identified. This may indicate that the genetic profiles of Chinese patients are different from those of other populations.
  
  
  CONCLUSIONS
  23 Chinese GA1 patients with varied clinical manifestations have been reported. 11 novel mutations in their GCDH gene were identified, indicating that the genetic profiles of Chinese GA1 patients differ from those of other populations.
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors: Qiao
authors: Q
authors: Wang
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors: Xiyuan
authors: X
authors: Li
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors: Yuan
authors: Y
authors: Ding
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors: Yupeng
authors: Y
authors: Liu
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors: Jinqing
authors: J
authors: Song
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. Electronic address: yanlingy@vip.sina.com.
authors: Yanling
authors: Y
authors: Yang
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000592:Amino Acid Metabolism, Inborn Errors / Q000178:diet therapy / Q000235:genetics* / Q000503:physiopathology*; D044466:Asian People / Q000235:genetics; D001928:Brain Diseases, Metabolic / Q000178:diet therapy / Q000235:genetics* / Q000503:physiopathology*; D002648:Child; D002681:China; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D050770:Glutaryl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017385:Sequence Homology
chemical_list: D050770:Glutaryl-CoA Dehydrogenase
keywords: Dystonia; Glutaric aciduria type 1 (GA1); Glutaryl-CoA dehydrogenase (GCDH); Late onset; Organic aciduria; Outcome