Glutamyl Ribose-5-Phosphate Storage Disease

Williams et al. (1984) reported the case of a 6-year-old boy with a history of seizures, progressive neurologic deterioration, and proteinuria. Physical examination showed mildly coarse facies, generalized hypotonia with muscle wasting, and optic atrophy. No organomegaly was found. The patient died of renal failure at age 8. X-linked recessive inheritance was suggested by the history of a similar disorder in a maternal uncle who had seizures at 9 months of age, followed by deterioration of speech and vision. He had had hypertension, nephrotic syndrome, optic atrophy, hyporeflexia, and severe retardation when he died in renal failure at 7 years of age. Electron microscopy of conjunctival and renal biopsies showed cytoplasmic storage and abnormal lysosomes. A compound identified as glutamyl ribose-5-phosphate was purified from the brain and kidney. This compound is the linkage group in ADP-ribosylation of proteins, a posttranslational modification which is an important regulatory process in gene expression and DNA repair. Williams et al. (1984) classified the disorder as a glycoproteinosis; classification as a lysosomal storage disease under stringent criteria requires identification of deficiency of a lysosomal enzyme. Deficiency of ADP-ribose protein hydrolase was postulated.