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: Xiyuan Li, Yuan Ding, Yupeng Liu, Yanyan Ma, Jinqing Song, Qiao Wang, Yanling Yang
• Journal: Brain & development (Brain Dev) Vol. 37 Issue 10 Pg. 952-9 (Nov 2015) ISSN: 1872-7131 [Electronic] Netherlands
• PMID: 25851806 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Pyroglutamate Hydrolase
• Glutathione Synthase
• Hydroxyproline

Topics

• Amino Acid Metabolism, Inborn Errors (diagnosis, genetics, metabolism, urine)
• Asian People
• Case-Control Studies
• Child, Preschool
• China
• Female
• Genetic Predisposition to Disease
• Glutathione Synthase (deficiency, genetics, metabolism, urine)
• Humans
• Hydroxyproline (urine)
• Infant
• Infant, Newborn
• Male
• Mutation
• Pyroglutamate Hydrolase (deficiency, genetics, metabolism, urine)