Pyroglutamic aciduria

There are two distinct types of GSH-S deficiency, both associated with mild chronic hemolysis in one type, hemolysis is the only clinical manifestation. In the other, the major clinical features are mental retardation, severe generalized muscle weakness, tremors, incoordination, hemolytic anemia, and metabolic acidosis. This second and much more severe type of GSH-S deficiency is also known as 5-oxopro-linurta or pyroglutamic aciduria. The difference in severity of these disorders reflects the fact that in the mild form, GSH-S deficiency is confined to the RBCs because in this disorder the GSH-S is unstable. GSH-S activity is present in adequate quantity in young RBCs, but it rapidly declines as the cells age, because the cells are unable to synthesize new molecules of GHS-S. Other cells of the body that have nuclei and ribosomes can compensate for accelerated denaturation of GSH-S by synthesizing more. On the other hand, in the severe systemic form of GSH-S deficiency, aE cells of the body have low activities of GSH-S because they cannot form this enzyme in adequate amounts. In both types of GSH-S deficiency, RBCs exhibit notable reduction in GSH concentration. 

The second newly discovered inborn error of amino acid metabolism, pyroglutamic aciduria, was reported by Jellum and co-workers (J3) late... 

Jellum, E., Marstein, L., Skullerud, K. and Munthe, E. (1983) Glutathione in pyroglutamic aciduria (5-oxoprolinuria) and rheumatoid arthritis. In A. Larsson (Ed.), Functions of Glutathione Biochemical, Physiological, Toxicological, and Clinical Aspects, Raven Press, New York, pp. 347-353. 

Glutathione synthetase deC Pyroglutamic aciduria (5 Oxoprolinuria Citrullinemia... 

Anemia (Hb) 4 Tyrosinemia type 1 Methylmalonic acidemia Pyroglutamic aciduria (5-oxoprolinuria) y-Glutamylcysleine synthetase def. Cobalamin C and D... 

Pseudo-corpus luteum deficiency Pseudo-neonatal adrenoleukodystrophy Pseudo-vaginal perineoscrotal hypospadia Pseudo-Zellweger syndrome Pterin carbinolamine-4a-dehydratase deficiency Purine nucleoside phosphorylase deficiency Pyroglutamic aciduria... 

Jellum, E., Kluge,T., Borresen, H.C., Stokke, O. andEldjam,L. (1970 Pyroglutamic aciduria - a new inborn error of metabolism. Scand. J. Clin. Lab. Invest., 26,327. 

Pyroglutamic aciduria (5-oxoprolinaemia) Pyroglutamic (L-2-pyrrolidine-5-carboxylic) acid Glutathione synthetase (EC6.3.2.3) 16.1... 

Larsson, A., Zetterstrom, R., Hagenfeldt, L., Anderson, R., Dreborg, S. and Homell, H. (1974), Pyroglutamic aciduria (5-oxoprolinuria), an inborn error of glutathione metabolism. Pediatr. Res., 8,852. 

Pyroglutamic aciduria (pyrrolidonecarboxylic aciduria, 5-oxo-L-prolinuria) (McKusick 26 613) was first reported by Jellum et aL (1970), who described a mentally subnormal 19-year-old man with spastic tetraparesis and cerebellar ataxia who was found to excrete 24 to 35 g of pyroglutamic acid per day in his urine, with blood and cerebrospinal fluid concentrations of 50 mg (100 ml) and 30 mg (100 ml) respectively. Amino acids were normal in all fluids... 

Fig. 16.1 The y-glutamyl cycle and pyroglutamic aciduria. Pyroglutamic acidura occurs because of a generalized deficient activity of glutathione (y-glutamyl) synthetase (EC 6.323).

Eldjarn, L., Jellum, E. and Stokke, O. (1972), Pyroglutamic aciduria studies on the enzyme block and on the metabolic origins of pyroglutamic acid. Clin. Ckim. Acta, 40,461. 

Griffith, O.W., Larsson, A. and Meister, A. (1977), Inhibition of y-glutamylcysteine synthetase by cystamine an approach to a therapy of 5-oxoprolinuria (pyroglutamic aciduria). Biochem. Biophys. Res. Commun., 79,919. 

Porath, U. and Schreier (1978), A family with pyroglutamic aciduria. Dtsch. Med. Wochenschr., 103,939. 

Stromme, J.H. and Eldjam, L. (1972), The metabolism of L-pyroglutamic acid in fibroblasts from a patient with pyroglutamic aciduria. The demonstration of a L-pyroglutamate hydrolase system. Scand. J. Clin. Lab. Invest., 29,335. 

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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