[Clinical spectrum of hypoxanthine-guanine phosphoribosyltransferase deficiency: study of 12 cases].

BACKGROUND: The hypoxanthine-guanine phosphoribosyltransferase deficiency (HGPRT) may have two clinical forms: that of the Lesch-Nyhan syndrome (complete HGPRT deficiency) and that of the Kelley-Seegmiller syndrome (partial HGPRT deficiency). The clinical and biochemical features of the HGPRT deficiency are not completely known.

METHODS: A series of 12 patients, 8 with the Lesch-Nyhan syndrome and 4 with the Kelley-Seegmiller syndrome are described. The plasma and urine concentrations of hypoxanthine, xanthine and uric acid were compared with those obtained in 20 normal subjects and 41 patients with primary gout. The molecular defect which determines the deficient HGPRT activity was studied in one patient with the Kelley-Seegmiller syndrome.

RESULTS: The 8 patients with the Lesch-Nyhan syndrome presented choreoathetosis, corticospinal motor system dysfunction, mental retardation and signs of self mutilation. The neurologic manifestations of the patients with the Kelley-Seegmiller syndrome were very heterogeneous: two patients had psychomotor retardation with spastic movement, one was mentally retarded with generalized dystonia and one patient only had gout with no neurologic manifestations. The erythrocytic HGPRT activity ranged between 0.28 and < 0.01 nmol/h and mg of hemoglobin in all the patients. Plasma and urine purine concentrations were very high, being greater than those in normal subjects and patients with gout (p < 0.01). A mutation was identified in exon 3 (substitution of guanine with thymine) conditioning the substitution of the normal glycine amino acid by valine (HGPRT Madrid) on molecular study.

CONCLUSIONS: The hypoxanthine-guanine phosphoribosyltransferase deficiency has a heterogeneous clinical expression. The activity of this enzyme in erythrocytes and the results of the metabolism of the purines do not allow prediction of the severity of the clinical manifestations.