Long-term clinical outcome in patients with glutathione synthetase deficiency.
OBJECTIVE
The objective was to determine the long-term clinical outcome and the effects of treatment of patients with glutathione synthetase (GS) deficiency (n = 28).


METHODS
The diagnosis was based on demonstration of a marked decrease in GS activity in erythrocytes or cultured fibroblasts in all patients and was supported by finding a decrease in erythrocyte or fibroblast glutathione, presence of 5-oxoprolinuria, or both. The treatment varied but usually included correction of acidosis and supplementation with vitamins C and/or E.


RESULTS
Sixteen patients were severely affected with neurologic symptoms such as seizures and psychomotor retardation; 7 had died at the time of the study. None of the severely affected patients had been treated with both vitamins C and E from the neonatal period. No significant difference was found in GS activity between patients with or without neurologic symptoms or in erythrocyte or fibroblast glutathione levels. Five patients had recurrent bacterial infections.


CONCLUSIONS
On the basis of clinical symptoms, patients with GS deficiency can be classified into 3 phenotypes: mild, moderate, and severe. Our results indicate that early supplementation with vitamins C and E may improve the long-term clinical outcome.
Ristoff
E
E
Department of Pediatrics, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
Mayatepek
E
E
Larsson
A
A
D000138:Acidosis / Q000188:drug therapy; D000328:Adult; D000743:Anemia, Hemolytic / Q000235:genetics; D001205:Ascorbic Acid / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005808:Genes, Recessive; D005981:Glutathione Synthase / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D009422:Nervous System Diseases / Q000235:genetics; D011596:Psychomotor Disorders / Q000235:genetics; D013997:Time Factors; D014810:Vitamin E / Q000627:therapeutic use
D014810:Vitamin E; D005981:Glutathione Synthase; D001205:Ascorbic Acid