Combined adenine phosphoribosyltransferase and N-acetylgalactosamine-6-sulfate sulfatase deficiency

We describe a Czech patient with combined adenine phosphoribosyltransferase (APRT) deficiency (2,8-dihydroxyadenine urolithiasis) and N-acetylgalactos amine-6-sulfate sulfatase (GALNS) deficiency (mucopolysaccharidosis Type IV A, Morquio disease A). Adenine and its extremely insoluble derivative, 2,8- dihydroxyadenine, were identified in the urine, and APRT deficiency was con firmed in erythrocytes. There was excessive excretion of keratan sulfate in the urine, and GALNS deficiency was confirmed in leukocytes. GALNS and APR T are both located on chromosome 16q24.3, suggesting that the patient had a deletion involving both genes. PCR amplification of genomic DNA indicated that a novel junction was created by the fusion of sequences distal to GALN S exon 2 and proximal to APRT exon 3, and that the size of the deleted regi on was approximately 100 kb. The deletion breakpoints were localized within GALNS intron 2 and APRT intron 2. Several other genes, including the alpha subunit of cytochrome B (CYBA), which is deleted or mutated in the autosom al form of chronic granulomatous disease, are located in the 16q24.3 region , but PCR amplification showed that this gene was present in the proband. A patient with hemizygosity for GALNS deficiency and APRT deficiency has bee n reported from Japan recently. These findings indicate that: (i) APRT is l ocated telomeric to GALNS; (ii) GALNS and APRT are transcribed in the same orientation (centromeric to telomeric); and (iii) combined APRT/GALNS defic iency may be more common than hitherto realized. (C) 1999 Academic Press.