Glutamyl Ribose 5-Phosphate Storage Disease

A patient with a lysosomal storage disease, progressive neurologic degeneration, and renal failure was found to have accumulated a low molecular weight nin-hydrin and phenol-HzS04 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 5phosphate. Quantitative analysis of the intact compound indicated a 1:l:l ratio for glutamic acid: ribose:phosphate. Brain was found to contain 0.96 pmol/g, wet weight, and kidney 0.60 pmol/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 ADPribose protein hydrolase (Okayama, H., Honda, M., and Hayaishi, 0. (1978) Proc. Nutl. Aeud. Sei. U. S. A. 75, 2254-2257).