Is 5-Oxoprolinase Deficiency More than Just a Benign Condition?

<b><i>Introduction:</i></b> Inherited 5-oxoprolinase (OPLAH) deficiency is a rare inborn condition characterized by 5-oxoprolinuria. The inherited condition of 5-oxoprolinuria, or pyroglutamic aciduria, is primarily caused by mutations in the genes that encode glutathione synthetase (GSS) and 5-oxoprolinase (OPLAH), which are enzymes involved in the gamma-glutamyl cycle in glutathione metabolism. We report a 3-year-old male patient with epilepsy and speech difficulty diagnosed as primary 5-oxoprolinuria due to a novel <i>OPLAH</i> gene mutation. <b><i>Case Presentation:</i></b> A 3-year-old boy who was delivered at full term in an uncomplicated birth to consanguineous parents presented with epilepsy at the age of 2 years. He did not speak fluently. He was using 5–10 words with decreased language fluency. His past medical history revealed postnatal macrocephaly, hydrocephalus, and well-controlled epilepsy with levetiracetam. Progressive cerebral atrophy, hypomyelination, ventriculomegaly, and corpus callosum hypoplasia were striking features in brain MRI. A urine sample was sent for organic acid analysis by gas chromatography-mass spectrometry (GC-MS); quantitation of 5-oxoproline by stable isotope dilution gave a value of 177.9 mmol/mol creatinine (reference values 25.8–92.2). Molecular genetic analysis of the OPLAH gene revealed a novel homozygous variant (<i>OPLAH</i> (NM_017570.5): c.1909C&gt;T p.Arg637Trp). <b><i>Conclusion:</i></b> We conclude that inherited 5-oxoprolinase deficiency is not a benign biochemical condition, and patients with 5-oxoprolinuria should be screened for it. The nature of this inherited metabolic disorder must be determined through long-term observation. We wish to emphasize the significance of molecular genetic analysis in symptomatic patients with persistently elevated levels of 5-oxoproline in the urine, as measured by organic acid analysis.