Journal of Inherited Metabolic Disease

, Volume 12, Issue 2, pp 120–130 | Cite as

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

  • J. Mårtensson
  • J. Gustafsson
  • A. Larsson


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.


Glutathione Taurine Sulphur Amino Acid Sulphur Amino Glutathione Concentration 
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Copyright information

© SSIEM and Kluwer Academic Publishers 1989

Authors and Affiliations

  • J. Mårtensson
    • 1
  • J. Gustafsson
    • 2
  • A. Larsson
    • 2
  1. 1.Department of Clinical ChemistryUniversity HospitalLinköping
  2. 2.Department of PediatricsUniversity HospitalUppsalaSweden

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