Hyperuricaemia and choreoathetosis in a child without mental retardation or self‐mutilation — a new HPRT variant

Abstract

A thirteen‐year‐old boy is described who had uric acid nephrolithiasis, spasticity and choreoathetosis, but no self‐mutilation or mental retardation. Initial studies suggested the presence of the classic Lesch‐Nyhan enzymatic defect; study of the metabolism of [8‐14C]hypoxanthine and [8‐14C]guanine in intact fibroblasts and careful analysis of the data indicated that this was not the case. This child represents a newly identified variant of the HPRT locus.

Genotype–phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder

“…Although it is important to acknowledge such exceptional cases, it also is important to avoid placing too much weight on unconfirmed and isolated reports, A B Figure 5 Correlations between residual enzyme activity and clinical severity in patient cells. Panel A is a box-whisker plot showing residual activities for Hprt as measured by the intact fibroblast assay for 56 patients previously reported (Itiaba et al, 1978;Bakay et al, 1979;Gottlieb et al, 1982;Warzok et al, 1982;Fattal et al, 1984;Lorentz et al, 1984;Mitchell and McInnes, 1984;Hersh et al, 1986;Tarle et al, 1991;Gilbert et al, 1992;Sege-Peterson et al, 1992;Jenkins et al, 1994;Erhard et al, 1997;Puig et al, 2001;Zoref-Shani et al, 2003Cherian and Crompton, 2005;Cossu et al, 2006;Jinnah et al, 2010;Sarafoglou et al, 2010;Torres et al, 2010). Panel B is a box-whisker plot showing residual activities for Hprt as measured by the intact erythrocyte assay for 54 patients previously reported (Shnier et al, 1972;Ludman et al, 1992;Sege-Peterson et al, 1992;Davidson et al, 1994;Willers et al, 1999;Puig et al, 2001;Augoustides-Savvopoulou et al, 2002;Bertelli et al, 2004;Kassimatis et al, 2005;Cossu et al, 2006;Garcia et al, 2008;de Gemmis et al, 2010;Corrigan et al, 2011).…”

Lesch‐nyhan variant: Dystonia, ataxia, near‐normal intelligence, and no self‐mutilation

“…Laboratory studies revealed an absence of HPRT enzyme activity in erythrocyte and fibroblast lysates, and in hair follicle assays (2). There was some ability to salvage purines, although only slightly more than typical Lesch-Nyhan patients, in an intact skin fibroblast metabolic assay ( 2 ) .…”