|Five Chinese patients with 5-oxoprolinuria due to glutathione synthetase and 5-oxoprolinase deficiencies|
|Li, Xiyuan; Ding, Yuan; Liu, Yupeng; Ma, Yanyan; Song, Jinqing; Wang, Qiao; Yang, Yanling|
|关键词||5-Oxoprolinuria Pyroglutamic aciduria Glutathione synthetase deficiency 5-Oxoprolinase deficiency GSS gene OPLAH gene|
|刊名||BRAIN & DEVELOPMENT|
|WOS标题词||Science & Technology|
|研究领域[WOS]||Neurosciences & Neurology|
|关键词[WOS]||GAP METABOLIC-ACIDOSIS ; INBORN-ERRORS|
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 3 years in Peking University First Hospital. OPLAH and GSS genes were analyzed.
Results: Patients were hospitalized between the age of 13 days to 1 year and 3 months 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_2815 delGGG 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 Q(10), 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. (C) 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
|项目编号||81471097 ; 2012BAI09B04|
|资助机构||National Nature Science Foundation of China ; 12th Five-year Plan National Key Technology R & ; D Program from the Ministry of Science and Technology|
|作者单位||Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China|
|Li, Xiyuan,Ding, Yuan,Liu, Yupeng,et al. Five Chinese patients with 5-oxoprolinuria due to glutathione synthetase and 5-oxoprolinase deficiencies[J]. BRAIN & DEVELOPMENT,2015,37(10):952-959.|
|APA||Li, Xiyuan.,Ding, Yuan.,Liu, Yupeng.,Ma, Yanyan.,Song, Jinqing.,...&Yang, Yanling.(2015).Five Chinese patients with 5-oxoprolinuria due to glutathione synthetase and 5-oxoprolinase deficiencies.BRAIN & DEVELOPMENT,37(10),952-959.|
|MLA||Li, Xiyuan,et al."Five Chinese patients with 5-oxoprolinuria due to glutathione synthetase and 5-oxoprolinase deficiencies".BRAIN & DEVELOPMENT 37.10(2015):952-959.|