Unusual Presentation of Kelley-Seegmiller Syndrome

• Published in: Nucleosides, nucleotides & nucleic acids Vol. 27; no. 6-7; pp. 648 - 655
• Main Authors: Sebesta, I., StibÅrková, B., Dvorakova, L., Hrebicek, M., Minks, J., Stolnaja, L., Vernerova, Z., Rychlik, I.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis Group 01-06-2008
• Subjects: Adult; Alleles; Female; gout; Heterozygote; Humans; hyperuricemia; Hypoxanthine Phosphoribosyltransferase - deficiency; Hypoxanthine Phosphoribosyltransferase - genetics; Hypoxanthine Phosphoribosyltransferase - metabolism; Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency; Lesch-Nyhan disease variants; Lesch-Nyhan Syndrome - enzymology; Lesch-Nyhan Syndrome - genetics; Lesch-Nyhan Syndrome - metabolism; Lesch-Nyhan Syndrome - pathology; Male; Middle Aged; Mutation; Pedigree; Purines - blood; Syndrome; X Chromosome Inactivation
• ISSN: 1525-7770; 1532-2335
• DOI: 10.1080/15257770802143863

Female carriers of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency have somatic cell mosaicism of HPRT activity and are healthy. We report a 50-year-old woman without gout or nephrolithiasis. She was never on allopurinol. Normal serum uric acid concentrations, increased plasma hypoxanthine, and xanthine were found. HPRT activity in erythrocytes was surprisingly low: at 8.6 nmol h
−1
mg
−1
haemoglobin. Mutation analysis revealed a heterozygous HPRT gene mutation, c.215A > G (p.Tyr72Cys). Assessment of X-inactivation ratio has shown that > 75% of the active X-chromosome bears the mutant allele and could explain these unusual, previously undescribed findings.