New insights into the genetics of 5-oxoprolinase deficiency and further evidence that it is a benign biochemical condition

Inherited 5-oxoprolinase (OPLAH) deficiency is a rare inborn condition characterised by 5-oxoprolinuria. To date, three OPLAH mutations have been described: p.H870Pfs in a homozygous state, which results in a truncated protein, was reported in two siblings, and two heterozygous missense changes, p.S...

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Bibliographic Details
Published in:European journal of pediatrics 2015-03, Vol.174 (3), p.407-411
Main Authors: Calpena, Eduardo, Deshpande, Anup Arunrao, Yap, Sufin, Kumar, Akhilesh, Manning, Nigel J., Bachhawat, Anand K., Espinós, Carmen
Format: Article
Language:English
Subjects:
Amino Acid Metabolism, Inborn Errors - genetics
Antibiotics
Chromatography
Creatinine
Diagnostic tests
Female
Genes, Recessive
Genetic Predisposition to Disease
Genetics
Heterozygote
Humans
Infant
Mass spectrometry
Medicine
Medicine & Public Health
Metabolism
Mutation
Mutation, Missense
Patients
Pediatrics
Proteins
Pyroglutamate Hydrolase - deficiency
Pyroglutamate Hydrolase - genetics
Scientific imaging
Short Communication
Siblings
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Summary:Inherited 5-oxoprolinase (OPLAH) deficiency is a rare inborn condition characterised by 5-oxoprolinuria. To date, three OPLAH mutations have been described: p.H870Pfs in a homozygous state, which results in a truncated protein, was reported in two siblings, and two heterozygous missense changes, p.S323R and p.V1089I, were independently identified in two unrelated patients. We describe the clinical context of a young girl who manifested 5-oxoprolinuria together with dusky episodes and who is compound heterozygote for two novel OPLAH variations: p.G860R and p.D1241V. To gain insight into the aetiology of the 5-oxoprolinase deficiency, we investigated the pathogenicity of all the reported missense mutations in the OPLAH gene. A yeast in vivo growth assay revealed that only p.S323R, p.G860R and p.D1241V affected the activity of the enzyme. Conclusion : Taken together, this report further suggests that hereditary 5-oxoprolinase deficiency is a benign biochemical condition caused by mutations in the OPLAH gene, which are transmitted in an autosomal recessive manner, but 5-oxoprolinuria may be a chance association in other disorders.
ISSN:0340-6199
1432-1076
DOI:10.1007/s00431-014-2397-0