title: Five Chinese patients with 5-oxoprolinuria due to glutathione synthetase and 5-oxoprolinase deficiencies.
abstract: OBJECTIVE
  5-Oxoprolinuria is a rare inherited metabolic disorder caused by a defective gamma-glutamyl cycle resulting from mutations in the genes encoding 5-oxoprolinase (OPLAH) and glutathione synthetase (GSS). No inherited 5-oxoprolinuria case has been reported in mainland China until now. In this study, clinical, biochemical, and genetic aspects of five Chinese 5-oxoprolinuria patients with OPLAH or GSS gene mutations were investigated.
  
  
  METHODS
  Three boys and two girls from five unrelated Chinese families with symptomatic 5-oxoprolinuria were identified within the past 3years in Peking University First Hospital. OPLAH and GSS genes were analyzed.
  
  
  RESULTS
  Patients were hospitalized between the age of 13days to 1year and 3months for hypersomnia, developmental retardation, feeding deficiency, vomiting, icterus and recurrent pneumonia. All patients had significantly elevated urine 5-oxoproline. Three novel mutations (c.1904G>A and c.2813_2815delGGG in Patient 1, c.2978G>T in Patient 2) on OPLAH, on GSS, one novel mutation (c.1252C>T in Patient 3) and a reported mutation (c.491G>A in Patients 3-5) were detected. Patient 4 has homozygous mutation c.491G>A, the others are heterozygous. After treatment by l-carnitine, vitamin E, B1, B2 and coenzyme Q10, three patients with GSS deficiency improved, but the two 5-oxoprolinase-deficient patients did not respond to treatment.
  
  
  CONCLUSIONS
  5-Oxoprolinase deficiency and GSS deficiency share some clinical and biochemical features. Genetic analysis is important for the deferential diagnosis. In this study, five Chinese patients had severe central nervous system damage. Antioxidant treatments were proved effective for the three patients with GSS deficiency but not for the two patients with 5-oxoprolinase deficiency.
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: Yanyan
authors: Y
authors: Ma
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.
authors: Qiao
authors: Q
authors: Wang
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: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000652:urine*; D044466:Asian People; D016022:Case-Control Studies; D002675:Child, Preschool; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D005981:Glutathione Synthase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism / Q000652:urine; D006801:Humans; D006909:Hydroxyproline / Q000652:urine*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D011752:Pyroglutamate Hydrolase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism / Q000652:urine
chemical_list: D011752:Pyroglutamate Hydrolase; D005981:Glutathione Synthase; D006909:Hydroxyproline
keywords: 5-Oxoprolinase deficiency; 5-Oxoprolinuria; GSS gene; Glutathione synthetase deficiency; OPLAH gene; Pyroglutamic aciduria