ABSTRACT
Female carriers of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency have somatic cell mosaicism of HPRT activity and are healthy. We report a 50-year-old woman without gout or nephrolithiasis. She was never on allopurinol. Normal serum uric acid concentrations, increased plasma hypoxanthine, and xanthine were found. HPRT activity in erythrocytes was surprisingly low: at 8.6 nmol h(-1) mg (-1) haemoglobin. Mutation analysis revealed a heterozygous HPRT gene mutation, c.215A > G (p.Tyr72Cys). Assessment of X-inactivation ratio has shown that > 75% of the active X-chromosome bears the mutant allele and could explain these unusual, previously undescribed findings.
Subject(s)
Hypoxanthine Phosphoribosyltransferase/deficiency , Lesch-Nyhan Syndrome/enzymology , Lesch-Nyhan Syndrome/genetics , Adult , Alleles , Female , Heterozygote , Humans , Hypoxanthine Phosphoribosyltransferase/genetics , Hypoxanthine Phosphoribosyltransferase/metabolism , Lesch-Nyhan Syndrome/metabolism , Lesch-Nyhan Syndrome/pathology , Male , Middle Aged , Mutation , Pedigree , Purines/blood , Syndrome , X Chromosome InactivationABSTRACT
In the present study, we have evaluated the effects of ethanol (ETOH) on luteinizing hormone releasing hormone (LHRH) secretion induced by N-methyl-DL-aspartic acid (NMA) in vitro and the ability of NMA to induce precocious puberty in vivo. For the in vitro experiments, the basal and NMA-stimulated release of LHRH from arcuate nucleus-median eminence (AN-ME) fragments obtained from immature female rats was measured by RIA following static incubation in medium consisting of Krebs-Ringer bicarbonate glucose buffer. Control vials contained medium only and the test vials contained medium plus ETOH doses of 30, 50, and 70 mM. These data demonstrate that ETOH did not alter basal LHRH release, but dose-dependently blocked (p < 0.01) the NMA-induced release of the peptide during anestrus, as well as first proestrus and estrus. For the in vivo experiment, 26-day-old females began receiving saline or saline-ETOH (3 g/kg) solution by gastric gavage daily at 12.30 p.m. Each day at 2.00 and 4.00 p.m., each of the animals received subcutaneous injections of a 40-mg/kg solution of NMA in saline. Other control animals received saline gastrically, as well as subcutaneously. The timing of puberty was assessed in all animals by monitoring vaginal opening (VO) and first diestrus (D1). The mean (+/- SEM) age at VO for animals in the non-ETOH group, which received NMA, was 31.7 +/- 0.40 days. Vaginal smears revealed that D1 occurred at a mean (+/- SEM) age of 33.0 +/- 0.42 days.(ABSTRACT TRUNCATED AT 250 WORDS)
