New insights into the genetics of 5-oxoprolinase deficiency and further evidence that it is a benign biochemical condition.
Eur J Pediatr
; 174(3): 407-11, 2015 Mar.
Article
in En
| MEDLINE
| ID: mdl-25129617
ABSTRACT
UNLABELLED 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyroglutamate Hydrolase
/
Mutation, Missense
/
Amino Acid Metabolism, Inborn Errors
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
/
Infant
Language:
En
Journal:
Eur J Pediatr
Year:
2015
Document type:
Article