In patients with defects in the synthesis, breakdown and metabolism of glutathione (GSH), like glutathione synthetase deficiency (GSD) and 5-oxoprolinase deficiency, urinary excretion of 5-oxoproline, an intermediate of the gamma-glutamyl cycle, is increased. We identified 20 patients with significantly elevated urinary excretion of 5-oxoproline (> or =150 mmol/mol creatinine) during 5 years of selective screening for organic acidurias. In 6 of them, 5-oxoprolinuria was a constant finding including three patients with GSD and one with 5-oxoprolinase deficiency. One patient with constant 5-oxoprolinuria had GM2 gangliosidosis and one was clinically unaffected. In 14 patients, 5-oxoprolinuria was a transient abnormality and most often associated with an inborn error of metabolism outside the gamma-glutamyl cycle. In 9 of them 5-oxoprolinuria was associated with a neonatal urea cycle defect, with tyrosinaemia type I or occurred during metabolic decompensation in propionic acidaemia or methylmalonic acidaemia. Additionally, transient 5-oxoprolinuria was associated with homocystinuria, Stevens-Johnson syndrome, paracetamol intoxication, vigabatrin medication or extreme prematurity.
Conclusion: 5-Oxoprolinuria is a more common condition than hitherto thought and is primarily associated with defects in the gamma-glutamyl cycle. However, several other inborn errors of metabolism and pathophysiological conditions must be taken into account when discovering 5-oxoprolinuria.