title: 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.
authors.affiliation: Section of Pediatric Nephrology, Children's Mercy Hospital, and University of Missouri-Kansas City School of Medicine, Kansas City, Missouri 64108, USA.
authors.forename: Tarak
authors.initials: T
authors.lastname: Srivastava
authors.forename: J Patrick
authors.initials: JP
authors.lastname: O'Neill
authors.forename: Majed
authors.initials: M
authors.lastname: Dasouki
authors.forename: Ari M
authors.initials: AM
authors.lastname: Simckes
mesh_terms: D058186:Acute Kidney Injury / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002648:Child; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020125:Mutation, Missense; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D013866:Thioguanine / Q000494:pharmacology; D014527:Uric Acid / Q000097:blood*
chemical_list: D014527:Uric Acid; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine