ab2006

Kelley-Seegmiller syndrome in a patient with complete hypoxanthine-guanine phosphoribosyltransferase deficiency

A. Cossu¹, V. Micheli², G. Jacomelli², A. Carcassi¹

¹Dipartimento-Struttura Clinica Medica-Patologia Speciale Medica, Cattedra e Scuola di Specializzazione in Reumatologia, Universitˆ degli Studi di Sassari; ²Dipartimento di Biologia Molecolare, Universitá degli Studi di Siena, Italy.

ABSTRACT
Different degrees of hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency are associated with hyperuricemia, uric acid nephrolithiasis and severe gout. Up to 25-30% of HPRT deficient patients, indicated as neurological variants or HPRT-related hyperuricemia with neurological dysfunction (HRND), may develop neurological manifestation, from mild to severe; the most serious ones manifesting in the devastating Lesch-Nyhan syndrome, characterized by choreoathetosis or self-mutilation. Here we present a 30 years old male patient suffering from gout and mild psycho-motor impairment without Lesch Nyhan disease despite severe HPRT deficiency residual activity 0.02% with hypoxanthine, no activity at all with guanine as a substrate. The Curto's theory that neurologic impairment is dependent on VGPRT/VHPRT ratio is not confirmed by our observations. The finding of such a severe HPRT deficiency in a non-Lesch-Nyhan patient needs further investigation. G6PD deficiency was also referred together with b-thalassemic trait. We have studied purine and pyridine nucleotide metabolism in the erythrocytes and discussed the literature. The bone marrow sample shows a megaloblastyc aspect.

Key words
HPRT, Lesch-Nyhan syndrome, Kelley-Seegmiller syndrome, gout.

This paper is supported from a grant of Sassari University (ex 60%).
Please address correspondence and reprint requests to: Prof. Aldo Carcassi, Istituto di Patologia Medica, Cattedra di Reumatologia, Universitˆ degli Studi di Sassari, Viale San Pietro 8, 07100 Sassari, Italy.
E-mail: carcassi@ssmain.uniss.it