Childhood hyperuricemia and acute renal failure resulting from a missense mutation in the HPRT gene
- PMID: 11891689
- DOI: 10.1002/ajmg.10217
Childhood hyperuricemia and acute renal failure resulting from a missense mutation in the HPRT gene
Abstract
A 6-year-old boy was determined to have partial hypoxanthine phosphoribosyl transferase (HPRT) enzyme deficiency without the phenotypic features of Lesch-Nyhan syndrome. He presented with recurrent acute renal failure (ARF) from hyperuricemia. Treatment with allopurinol prevented further attacks of renal failure. T lymphocyte cultures were used to sequence the HPRT cDNA and a novel single nucleotide substitution at codon 65 in exon 3 was found (193C>T, 65leu>phe). This mutation was confirmed by genomic DNA sequencing and was also detected in his heterozygous, asymptomatic mother and sister. Unlike the cells from patients with classic Lesch-Nyhan syndrome, the in vitro cultures of our patient's T-lymphocytes did not proliferate in the presence of purine analogue 6-thioguanine (TG). This report highlights the unusual occurrence of recurrent ARF in a child with partial HPRT enzyme deficiency. The absence of TG resistance in vitro with this mutation shows that even small alterations in enzyme activity in vivo can result in disease symptoms, in this instance, hyperuricemia sufficient to cause ARF. Atypical HPRT mutations should also be considered in cases of unusual renal failure, because correct diagnosis can allow appropriate treatment, as well as informed genetic counseling.
Similar articles
-
Eighteen-year follow-up of a patient with partial hypoxanthine phosphoribosyltransferase deficiency and a new mutation.Pediatr Nephrol. 2005 Sep;20(9):1346-8. doi: 10.1007/s00467-005-1935-4. Epub 2005 Jun 18. Pediatr Nephrol. 2005. PMID: 15965771
-
The spectrum of inherited mutations causing HPRT deficiency: 75 new cases and a review of 196 previously reported cases.Mutat Res. 2000 Oct;463(3):309-26. doi: 10.1016/s1383-5742(00)00052-1. Mutat Res. 2000. PMID: 11018746 Review.
-
[A Japanese family with Lesch-Nyhan syndrome resulting from a new point mutation in hypoxanthine-guanine phosphoribosyltransferase gene].No To Shinkei. 1997 Nov;49(11):1009-13. No To Shinkei. 1997. PMID: 9396032 Japanese.
-
[Complete and partial deficiency of HPRT].Nihon Rinsho. 1996 Dec;54(12):3315-20. Nihon Rinsho. 1996. PMID: 8976112 Review. Japanese.
-
Genetic analysis of the HPRT mutation of Lesch-Nyhan syndrome in a Chinese family.Zhonghua Yi Xue Za Zhi (Taipei). 1995 Dec;56(6):359-66. Zhonghua Yi Xue Za Zhi (Taipei). 1995. PMID: 8851475
Cited by
-
Effect of hypoxanthine, antioxidants and allopurinol on cholinesterase activities in rats.J Neural Transm (Vienna). 2013 Sep;120(9):1359-67. doi: 10.1007/s00702-013-0989-x. Epub 2013 Feb 12. J Neural Transm (Vienna). 2013. PMID: 23400363
-
Genotype-phenotype correlations in Lesch-Nyhan disease: moving beyond the gene.J Biol Chem. 2012 Jan 27;287(5):2997-3008. doi: 10.1074/jbc.M111.317701. Epub 2011 Dec 7. J Biol Chem. 2012. PMID: 22157001 Free PMC article.
-
Attenuated variants of Lesch-Nyhan disease.Brain. 2010 Mar;133(Pt 3):671-89. doi: 10.1093/brain/awq013. Epub 2010 Feb 22. Brain. 2010. PMID: 20176575 Free PMC article. Review.
-
Lesch-Nyhan syndrome presenting with acute renal failure in a 3-day-old newborn.Pediatr Nephrol. 2008 Jan;23(1):155-8. doi: 10.1007/s00467-007-0588-x. Epub 2007 Aug 16. Pediatr Nephrol. 2008. PMID: 17701224
-
Partial hypoxanthine-guanine phosphoribosyltransferase deficiency presenting as acute renal failure.Pediatr Nephrol. 2005 Dec;20(12):1811-3. doi: 10.1007/s00467-005-2065-8. Epub 2005 Oct 21. Pediatr Nephrol. 2005. PMID: 16240158
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous