Glutathione Synthetase Deficiency: The clinical management of GS deficient patients is aimed at correction of acidosis, prevention of haemolytic crises and support of endogenous defence against reactive oxygen species (ROS). In the neonatal period, correction of metabolic acidosis, electrolyte imbalances, treatment of anaemia and excessive hyperbilirubinaemia are of crucial importance. Correction of acidosis can be reached through bicarbonate, citrate or tris-hydroxymethyl aminomethane (THAM). Doses of up to 10 mmol/kg/day, or even higher in episodes of acute infections, may be required. Repeated blood transfusions may be necessary in patients with massive haemolysis. Drugs and foods known to precipitate haemolytic crises in patients with glucose- 6-phosphatase dehydrogenase deficiency should be avoided. Successful treatment with erythropoietin has been reported in one patient. Early supplementation with vitamin E and vitamin C are thought to replenish the lack of GSH as a scavenger of free radicals. Recommended doses are 10 mg/kg/day for vitamin E and 100 mg/kg/day for vitamin C. A longterm follow-up study of 28 patients suggested that early supplementation with both vitamins may prevent CNS damage and improve the long-term clinical outcome in GS-deficient patients. The value of N-acetylcysteine, which is known to protect cells from oxidative stress in vitro, in the treatment of GS deficiency is controversial. It was suggested that the low intracellular GSH concentrations and cysteine availabilty might be increased by N-acetylcysteine. However, supplementation with N-acetylcysteine should not be recommended, because it was shown at least in cultured fibroblasts that patients with GS deficiency accumulate cysteine, which is known to be neurotoxic in excessive amounts. A therapeutic trial with orally administered GSH showed no lasting benefit in two patients with GS deficiency. GSH esters, lipid-soluble preparations which are easily transported into cells where they are converted into GSH, have been tried in animal models of GSH deficiency and in two patients with GS deficiency. However, associated toxic effects due to production of alcohols as a by-product during hydrolysis to release GSH make them of limited use. In vitro studies have shown that addition of S-acetylglutathione to the medium of cultured fibroblasts from patients with GS deficiency normalised intracellular GSH content. Owing to the rarity of the disease and the heterogeneity of the clinical condition the prognosis for individual patients is difficult to predict. Early diagnosis, correction of acidosis and early supplementation with vitamin E and vitamin C appear to be the most important factors regarding the survival and the long-term outcome. Hawkinsinuria: Symptoms in infancy respond to a return to breastfeeding or a diet restricted in tyrosine and phenylalanine along with vitamin C supplementation. The condition is asymptomatic after the 1st year of life, and affected infants are reported to have developed normally. 5-Oxoprolinase Deficiency: No specific treatment has been proposed or tried. (T527)