title: 5-Oxoprolinuria in patients with and without defects in the gamma-glutamyl cycle.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Division of Metabolic Diseases, University Children's Hospital, Heidelberg, Germany. ertan_mayatepek@ukl.uni-heidelberg.de
authors: E
authors: E
authors: Mayatepek
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005978:Glutathione / Q000378:metabolism*; D005981:Glutathione Synthase / Q000172:deficiency*; D006801:Humans; D007223:Infant; D008661:Metabolism, Inborn Errors / Q000652:urine*; D011752:Pyroglutamate Hydrolase / Q000172:deficiency*; D011761:Pyrrolidonecarboxylic Acid / Q000652:urine*
chemical_list: D011752:Pyroglutamate Hydrolase; D005981:Glutathione Synthase; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid