CLINICAL SPECTRUM OF HYPOXANTHINE-GUANINE PHOSPHORRIBOSYLTRANSFERASE DEFICIENCY - STUDY OF 12 CASES

BACKGROUND: The hypoxanthine-guanine phosphorribosyltransferase defici ency (HGPRT) may have two clinical forms: that of the Lesch-Nyhan synd rome (complete HGPRT deficiency) and that of the Kelley-Seegmiller syn drome (partial HGPRT deficiency). The clinical and biochemical feature s 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 obta ined in 20 normal subjects and 41 patients with primary gout The molec ular defect which determines the deficient HGPRT activity was studied in one patient with the Kelley-Seegmiller syndrome. RESULTS: The 8 pat ients with the Lesch-Nyhan syndrome presented choreoathetosis, cortico spinal motor system dysfunction, mental retardation and signs of self mutilation. The neurologic manifestations of the patients with the Kel ley-Seegmiller syndrome were very heterogeneous: two patients had psyc homotor retardation with spastic movement one was mentally retarded wi th generalized dystonia and one patient only had gout with no neurolog ic manifestations. The erythrocytic HGPRT activity ranged between 0.28 and < 0.01 nmol/h and mg of hemaglobin in all the patients. Plasma an d 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) conditioni ng the substitution of the normal glycine aminoacid by valine (HGPRT M adrid) on molecular study. CONCLUSIONS: The hypoxanthine-guanine phosp horribosyltransferase deficiency has a heterogeneous clinical expressi on. 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.