Progressive Neurologic Deterioration and Renal Failure Due to Storage of Glutamyl Ribose-5-Phosphate

• Published in: The New England journal of medicine Vol. 311; no. 3; pp. 152 - 155
• Main Authors: Williams, Julian C, Butler, Ian J, Rosenberg, Harvey S, Verani, Regina, Scott, Charles I, Conley, Susan B
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 19.07.1984
• Subjects: Adenosine diphosphate; ADP-ribosylation; Age; Amino acids; Atrophy; Biological and medical sciences; Biopsy; Brain - metabolism; Brain - ultrastructure; Brain Diseases, Metabolic - etiology; Brain Diseases, Metabolic - pathology; Carbohydrates; Child; Cytoplasm; Disease; DNA repair; EEG; Electron microscopy; Enzymes; Errors of metabolism; Gene expression; Genetic Linkage; Glycoproteins; Granular materials; Histones - metabolism; Humans; Kidney - metabolism; Kidney - ultrastructure; Kidney Failure, Chronic - etiology; Kidney Failure, Chronic - pathology; Kidneys; Lipids (lysosomal enzyme disorders, storage diseases); Liver - ultrastructure; Lysosomes; Lysosomes - enzymology; Male; Medical sciences; Metabolic diseases; Metabolic disorders; Microscopy; Optic atrophy; Organic acids; Pediatrics; Pentosephosphates - metabolism; Proteins; Proteinuria; Renal failure; Ribose; Ribosemonophosphates - metabolism; Ribosylation; Rodents; Seizures; Sex Chromosomes; Skin; Storage diseases; Urine; Human; Storage disease; Sex linked character; Nervous system diseases; Renal failure; Metabolic diseases; Hereditary; Child
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM198407193110305

A six-year-old boy presented with a history of seizures, progressive neurologic deterioration, and proteinuria. Physical examination revealed mildly coarse facies, failure to thrive, generalized hypotonia with muscle wasting, and optic atrophy; there was no organomegaly. The family history suggested an X-linked recessive inheritance. The electroencephalogram, electroretinogram, evoked potentials, and computed axial tomography of the brain were abnormal. Urine oligosaccharide chromatography, urine amino acids and organic acids, and results of leukocyte and fibroblast lysosomal-enzyme assays for the known storage diseases were normal; however, conjunctival and renal biopsy specimens contained enlarged lysosomes on electron microscopy. The patient had progressive neurologic deterioration and died of renal failure at eight years of age. A compound identified as glutamyl ribose-5-phosphate was purified from the brain (0.96 μmol per gram, wet weight) and kidney (0.60 μmol per gram, wet weight). This compound is the linkage group in ADP-ribosylation of proteins, an important regulatory process in gene expression and DNA repair. We believe this new disorder represents a glycoproteinosis that results in the cytoplasmic storage of glutamyl ribose-5-phosphate. (N Engl J Med 1984; 311:152–5.) THE elucidation of the molecular defect in Pompe's disease in 1963 led to the concept of lysosomal storage diseases. Since then, a number of inborn errors of metabolism have been shown to result in the accumulation of carbohydrate-containing compounds within the lysosome. 1 , 2 In addition to the mucopolysaccharidoses and gangliosidoses, a distinct class due to defects in the degradation of the carbohydrate moiety of glycoproteins has been recognized. 3 Although there are a number of known structurally different linkage groups for the attachment of carbohydrate to amino acids in glycoproteins, the only known disorder of catabolism of these linkage groups is aspartylglucosaminuria. . . .