A therapeutic trial with N-acetylcysteine in subjects with hereditary glutathione synthetase deficiency (5-oxoprolinuria).
In a therapeutic trial, the effect of short-term low-dosage N-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 gamma-glutamylcysteine levels were increased. In plasma, the glutathione concentrations were similarly decreased, but no gamma-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 with N-acetylcysteine (5 mg/kg x 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 gamma-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 that N-acetylcysteine may be of value in increasing the low intracellular glutathione concentrations and cysteine availability in patients with hereditary glutathione synthetase deficiency.
Mårtensson
J
J
Department of Clinical Chemistry, University Hospital, Linköping, Sweden.
Gustafsson
J
J
Larsson
A
A
D000111:Acetylcysteine / Q000627:therapeutic use*; D000293:Adolescent; D000603:Amino Acids, Sulfur / Q000097:blood / Q000652:urine; D005260:Female; D005978:Glutathione / Q000097:blood / Q000652:urine; D005981:Glutathione Synthase / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D010453:Peptide Synthases / Q000172:deficiency*; D011761:Pyrrolidonecarboxylic Acid / Q000097:blood / Q000652:urine
D000603:Amino Acids, Sulfur; D010453:Peptide Synthases; D005981:Glutathione Synthase; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid; D000111:Acetylcysteine