Abstract
Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is a disorder of purine metabolism responsible for Lesch-Nyhan Disease (LND) and its variants, HPRT-related hyperuricemia with neurologic dysfunction (HND) and HPRT-related hyperuricemia (HRH). The objective of this study was to characterize a cohort of Argentine patients with HPRT deficiency diagnosed in a single center. Results: Twenty nine patients were studied, including 12 LND, 15 HND and 2 HRH. The average onset age was 0.64 years for LND with motor delay as the main manifestation, 8.84 years for HND and 2.5 years for HRH; nephrological manifestations predominated as presenting features in these variants. The average diagnosis age was 3.58 years for LND, 17.21 years for HND and 2.5 years for HRH. Clinical heterogeneity was more evident in HND, even in members of the same family. All patients presented hyperuricemia and no detectable HPRT activity in erythrocyte lysate. The molecular study allowed to identify 9 different mutations in HPRT1 gene from 24 patients (11 independent pedigrees) and to establish genotype-phenotype correlation. In conclusion, this study describes the genotypic/phenotypic spectrum of HPRT deficiency in Argentine patients and highlights the need to increase awareness about the suspicion of these diseases, especially the LND variants with high clinical heterogeneity.
Highlights
Hypoxanthine-guanine phosphoribosyltransferase (HPRT; EC 2.4.2.8) deficiency (MIM 308000) is an X-linked genetic defect of the purine salvage pathway whereby purine bases are recycled into nucleotides[1,2]
The present study describes a cohort of 29 Argentine patients with HPRT deficiency, including both Lesch-Nyhan Disease (LND) and its attenuated variants, diagnosed in a single referral center (CEMECO, Children’s Hospital of Córdoba, Argentina)
This study represents the serial recognition of HPRT deficiency with classical phenotype of LND and its variants in Argentina
Summary
Hypoxanthine-guanine phosphoribosyltransferase (HPRT; EC 2.4.2.8) deficiency (MIM 308000) is an X-linked genetic defect of the purine salvage pathway whereby purine bases are recycled into nucleotides[1,2]. The HPRT enzyme catalyzes the transfer of the 5-phosphoribosyl group from 5-phosphoribosyl-1-. Pyrophosphate (PRPP) to a purine base hypoxanthine or guanine Received November 30, 2020, and in revised form February 02, 2021. Accepted to form IMP or GMP, respectively. The metabolic consequence for publication February 09, 2021. Of HPRT deficiency is an increase of de novo purines synthesis, which leads to increased production of uric acid, causing a variety of renal and joint symptoms. HPRT deficiency causes an increased in the concentration of hypoxanthine, which is not reused, and contributes to uric acid increases[2,3]. Corresponding Author: Laura Laróvere, Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Hospital de Niños de la Santísima Trinidad Clínica Pediátrica, Centro de Estudio de las Metabolopatías Congénitas, Córdoba, Argentina
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