A therapeutic trial withN-acetylcysteine in subjects with hereditary glutathione synthetase deficiency (5-oxoprolinuria)


In a therapeutic trial, the effect of short-term low-dosageN-acetylcysteine supplementation on glutathione metabolism was investigated in two patients with hereditary glutathione deficiency (5-oxoprolinuria). Clinical and neurophysiological examinations of the patients indicated progressive neurological damage. The pretreatment concentrations of total and free glutathione in leukocytes were 15–20% of normal, whereas the corresponding γ-glutamylcysteine levels were increased. In plasma, the glutathione concentrations were similarly decreased, but no γ-glutamylcysteine was detected. Total glutathione in erythrocytes was markedly decreased. Low urinary excretion of cysteinylglycine, cyst(e)ine, taurine,N-acetylcysteine, mercaptolactate and mercaptoacetate and reduced leukocyte taurine levels constituted additional evidence of decreased intracellular availability of cysteine, i.e. glutathione. Oral supplementation withN-acetylcysteine (5 mg/kg × 3/day) had no effect on acid-base balance, erythrocyte glutathione levels or 5-oxoproline concentrations in plasma and urine. In leukocytes, the glutathione concentrations were increased by 20–30%, whereas the γ-glutamylcysteine levels were essentially unaltered. In parallel, the urinary excretion of cysteinylglycine was increased and the leukocyte levels and urinary outputs of sulphur amino acids were restored. No side-effects of the treatment were noted. The results indicate thatN-acetylcysteine may be of value in increasing the low intracellular glutathione concentrations and cysteine availability in patients with hereditary glutathione synthetase deficiency.

DOI: 10.1007/BF01800713

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@article{Mrtensson1989ATT, title={A therapeutic trial withN-acetylcysteine in subjects with hereditary glutathione synthetase deficiency (5-oxoprolinuria)}, author={Ph.D. J. M{\aa}rtensson and J. Gustafsson and A. Larsson}, journal={Journal of Inherited Metabolic Disease}, year={1989}, volume={12}, pages={120-130} }