Mild Lesch-Nyhan disease in a boy with a null-mutation in HPRT1: an exception to the known genotype-phenotype correlation: three-year follow up.

Lesch-Nyhan disease and its attenuated variants are caused by deficiency of the purine salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HPRT). HPRT deficiency results in a continuous spectrum of clinical phenotypes though all include overproduction of uric acid with nephrolithiasis, renal failure, gouty arthritis and tophi.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 have previously presented a 10-year-old boy with a LND variant phenotype due to a deletion of exon 5 of HPRT1 predicted to fully abolish HPRT activity. Metabolic analysis confirmed lack of significant residual enzyme activity. He presented with hyperuricemia, hypotonia, developmental delay, extrapyramidal and pyramidal involvement. 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. He is currently 13-years-old and has yet to show any signs of self-injurious or maladaptive behaviour. We furthermore present our experience with oral baclofen in this patient.