Glutathione synthetase deficiency

Debieu D, Deschavanne PJ, Midander J, Larsson A, Malaise EP (1985) Survival curves of glutathione synthetase deficient human fibroblasts correlation between radiosensitivity in hypoxia and glutathione synthetase activity. Int J Radiat Biol 48 525-543 Debije MG, Milano MT, Bernhard WA (1999) DNA responds to ionizing radiation as an insulator not as a molecular wire". Angew Chem Int Ed Engl 38 2752-2756 Debije MG, Razskazovskiy Y, Bernhard AW (2001) The yield of strand breaks resulting from direct-type effects in crystalline DNA X-irradiated at 4 K and room temperature. J Am Chem Soc 123 2917-2918... 

Denison L, Haigh A, D Cunha G, Martin RF (1992) DNA ligands as radioprotectors Molecular studies with Hoechst 33342 and Hoechst 33258. Int J Radiat Biol 61 69-81 Deschavanne PJ, Debieu D, Chavaudra N, Malaise EP (1985) Radiosensitizing and cytotoxic properties of misonidazole on glutathione synthetase deficient human fibroblasts. Int J Radiat Biol 48 213-221... 

Corrons JL, Alvarez R, Pujades A, Zarza R, Oliva E, Lasheras G, et al. Hereditary non-spherocytic haemolytic anaemia due to red blood cell glutathione synthetase deficiency in four unrelated patients from Spain clinical and molecular studies. Br J Haematol 2001 112 475-82. 

Spielberg SP, Garrick MD, Corash LM, Butler JD, Tietze F, Rogers L, et al. Biochemical heterogeneity in glutathione synthetase deficiency. J Chn Invest 1978 61 1417-20. 

Larrson A, Anderson ME. Glutathione synthetase deficiency and other disorders of the y-glutamyl cycle. In Scriver CR, Beaudet AL, Valle D, Sly WS, et al., eds. The Metabolic and Molecular Bases of Inherited Disease, vol II, 8th Ed. New York McGraw-Hill, 2001 2205-2216. 

Oxoprolinase deficiency has been identified in eight patients, who lack a consistent clinical syndrome. Urinary excretion of 5-oxoproline is elevated but less than in glutathione synthetase deficiency. Erythrocytes contain an incomplete y-glutamyl cycle they lack both y-glutamyl transpeptidase and 5-oxoprolinase. 

Table 9 2 2. Glutathione synthetase deficiency (moderate, severe)...

The only disorder of the y-glutamyl cycle for which treatment principles have been developed is glutathione synthetase deficiency (9.2) [1]. The initial symptoms in the neonatal period may be metabolic acidosis and jaundice. Acidosis usually needs to be corrected with sodium bicarbonate, THAM or sodium citrate. Patients may benefit from oral administration of vitamin E (10 mg/kg/day) and vitamin C (100 mg/kg/day). Trials have also been made with N-acetylcysteine and glutathione esters which increased glutathione in leukocytes and plasma. Both these compounds lead to increased intracellular levels of glutathione. However, no decrease in the excretion of 5-oxoprolinuria has been reported. 

Ristoff E, Mayatepek E, Larsson A (2001) Long-term clinical outcome in patients with glutathione synthetase deficiency. / Fed 139(1) 79-84. 

Njalsson R, Carlsson K, Olin B, Carlsson B, Whitbred A, Polekhina G, Parker MW, Norgren S, Mannervik B, Board P, Larsson A (2000) Analysis of key missense mutations in patients with glutathione synthetase deficiency. Biochem. J. 349 275-279. 

Wellner, V.P., Sekura, R., Meister, A. andLarsson, A. (1974), Glutathione synthetase deficiency, an inborn error of metabolism involving the y-glutamyl cycle in patients with 5-oxoprolinuria (pyroglutamic aciduria). Proc. Natl. Acad. Sci. U.S.A., 71, 2505. 

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