Hypoxanthine-guanine phosphoribosyltransferase (
HPRT) deficiency results in a continuous spectrum of clinical phenotypes though all include overproduction of
uric acid with hyperuricaemia,
urate nephrolithiasis and
gout. HPRT1 mutations that result in very low or no
HPRT enzyme activities are generally associated with the classic
Lesch-Nyhan disease (LND) phenotype with
intellectual disability, motor handicap and self-injurious behaviour. Mutations that permit a higher residual
HPRT activity are seen in some patients with the milder LND variant phenotypes with varying degrees of cognitive, motor handicap and maladaptive behaviour without recurrent self-injury. We present a boy with a LND variant phenotype due to a deletion of exon 5 of HPRT1 predicted to fully abolish
HPRT activity. Metabolic analysis confirms lack of significant residual
enzyme activity. The boy, currently age 10, presented with hyperuricaemia,
hypotonia, developmental delay and extrapyramidal and pyramidal involvement. He has never shown any signs of self-injurious or maladaptive behaviour. This boy is one of the rare cases with a suspected null mutation in HPRT1 that associates with a milder than expected phenotype with lack of self-injurious behaviour. Key Clinical Message HPRT1 mutations that result in very low or no
hypoxanthine-guanine phosphoribosyltransferase enzyme activities are generally associated with the classic
Lesch-Nyhan disease. This report presents one of the rare cases with a null mutation in the HPRT1 gene that associates with a milder than expected phenotype with lack of self-injurious behaviour.