EFFECT OF ASCORBATE OR N-ACETYLCYSTEINE TREATMENT IN A PATIENT WITH HEREDITARY GLUTATHIONE SYNTHETASE DEFICIENCY

A 45-month-old girl with 5-oxoprolinuria (pyroglutamic aciduria), hemo lysis, and marked glutathione depletion caused by deficiency of glutat hione synthetase was followed before and during treatment with ascorba te or N-acetylcysteine. High doses of ascorbate (0.7 mmol/kg per day) or N-acetylcysteine (6 mmol/kg per day) were given for 1 to 2 weeks wi thout any obvious deleterious side effects. Ascorbate markedly increas ed lymphocyte (4-fold) and plasma (8-fold) levels of glutathione. N-Ac etylcysteine also increased lymphocyte (3.5-fold) and plasma (6-fold) levels of glutathione. After these treatments were discontinued, lymph ocyte and plasma glutathione levels decreased rapidly to pretreatment levels. Ascorbate treatment was extended for 1 year, and lymphocyte (4 -fold) and plasma (2- to 5-fold) glutathione levels remained elevated above baseline. In parallel, the hematocrit increased from 25.4% to 32 .6%, and the reticulocyte count decreased from 11% to 4%. The results demonstrate that ascorbate and N-acetylcysteine can decrease erythrocy te turnover in patients with hereditary glutathione deficiency by incr easing glutathione levels.