Recessive X-linked hyperuricemia with gout and renal damage, normal activity of hypoxanthine phosphoribosyltransferase and resistance to azaguanine.
A family is reported where four males have developed hyperuricemia, renal damage and, except for the youngest person affected, gout at an early age. The disease appears to be inherited as an X-linked recessive metabolic error. Clinically the patients have developed classical, tophaceous gout before the age of 25 and have suffered repeated attacks of renal colic. Renal tubular damage with decreased ability to concentrate and acidify urine was seen in a family member of only 16 years of age. Progressive renal failure seems to develop slowly. None in the family has shown neurologic symptoms, and two of the four affected men are apparently of at least average intelligence, two slightly below average. One female carrier has repeatedly passed uric acid stones. Studies of the red blood cell lysate have shown a normal activity of enzyme hypoxanthine phosphoribosyltransferase, and an increased level of adenine phosphoribosyltransferase. Skin fibroblasts from affected family members grew normally in the presence of 8-azaguanine. Administration of azathioprine to the patients did not decrease their serum uric acid levels. This is the first family described with this type of disorder of the purine metabolism.
D000228:Adenine Phosphoribosyltransferase / Q000097:blood; D000293:Adolescent; D000328:Adult; D001375:Azaguanine / Q000494:pharmacology*; D001379:Azathioprine / Q000627:therapeutic use; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005808:Genes, Recessive; D006073:Gout / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000097:blood*; D007674:Kidney Diseases / Q000097:blood / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000097:blood / Q000235:genetics*; D014527:Uric Acid / Q000097:blood*
D014527:Uric Acid; D000228:Adenine Phosphoribosyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase; D001379:Azathioprine; D001375:Azaguanine