Childhood hyperuricemia and acute renal failure resulting from a missense mutation in the HPRT gene.
Document Type
Article
Publication Date
3-15-2002
Identifier
DOI: 10.1002/ajmg.10217
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.
Journal Title
American journal of medical genetics
Volume
108
Issue
3
First Page
219
Last Page
222
MeSH Keywords
Acute Kidney Injury; Base Sequence; Cell Division; Child; DNA; DNA Mutational Analysis; Erythrocytes; Humans; Hypoxanthine Phosphoribosyltransferase; Male; Mutation, Missense; T-Lymphocytes; Thioguanine; Uric Acid
Recommended Citation
Srivastava, T., O'Neill, J. P., Dasouki, M., Simckes, A. M. Childhood hyperuricemia and acute renal failure resulting from a missense mutation in the HPRT gene. American journal of medical genetics 108, 219-222 (2002).
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