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.