Glutamyl ribose 5-phosphate storage disease. A hereditary defect in the degradation of poly(ADP-ribosylated) proteins.

A patient with a lysosomal storage disease, progressive neurologic degeneration, and renal failure was found to have accumulated a low molecular weight ninhydrin and phenol-H2SO4 reactive compound. Amino acid analysis and gas chromatography-mass spectrometry identified a glutamic acid moiety. Direct insertion mass spectrometry proved the carbohydrate portion to be a sugar phosphate. NaB3H4 reduction and borate electrophoresis, paper chromatography, and enzymatic digestion indicated the presence of ribose 5-phosphate. Quantitative analysis of the intact compound indicated a 1:1:1 ratio for glutamic acid: ribose:phosphate. Brain was found to contain 0.96 mumol/g, wet weight, and kidney 0.60 mumol/g, wet weight, of glutamyl ribose 5-phosphate. This substance is the linkage region in ADP-ribosylation of histones and other proteins. It is suggested that the primary defect in this patient is a genetic abnormality of ADP-ribose protein hydrolase (Okayama, H., Honda, M., and Hayaishi, O. (1978) Proc. Natl. Acad. Sci. U. S .A. 75, 2254-2257).