Harkness R A, McCreanor G M, Watts R W
Division of Inherited Metabolic Diseases, MRC Clinical Research Centre, Middlesex, UK.
J Inherit Metab Dis. 1988;11(3):239-52. doi: 10.1007/BF01800365.
Purine metabolism in the Lesch-Nyhan syndrome has been re-examined in 10 patients. Hypoxanthine and xanthine concentrations in plasma and CSF and urinary excretion have been studied, on and off allopurinol treatment, using high performance liquid chromatographic methods. Accumulation of the substrate, hypoxanthine, of the missing hypoxanthine guanine phosphoribosyltransferase (HPRT) enzyme, is more marked in urine and in CSF than in plasma. The greater increase in CSF is consistent with the most metabolically active tissue, brain, showing the most marked functional changes. The function of HPRT seems to be the recycling of hypoxanthine which is released from tissues in increasing quantities as energy use, ATP 'turnover', in the tissue increases. The existing screening method for HPRT deficiency, the ratio of the urinary concentration of urate to that of creatinine, shows overlap between the values in severe HPRT deficiency and in controls; this overlap is not found with a urinary hypoxanthine/creatinine molar concentration ratio.
对10例莱施-奈恩综合征患者的嘌呤代谢进行了重新研究。采用高效液相色谱法，在使用别嘌呤醇治疗前后，对血浆、脑脊液中的次黄嘌呤和黄嘌呤浓度以及尿排泄情况进行了研究。缺失的次黄嘌呤鸟嘌呤磷酸核糖转移酶（HPRT）的底物次黄嘌呤在尿液和脑脊液中的蓄积比在血浆中更为明显。脑脊液中更大的增加与代谢最活跃的组织——大脑——显示出最明显的功能变化相一致。HPRT的功能似乎是次黄嘌呤的再循环，随着组织中能量利用（ATP周转）的增加，次黄嘌呤从组织中释放的量也在增加。现有的HPRT缺乏筛查方法，即尿酸与肌酐的尿浓度比值，在严重HPRT缺乏患者和对照组的值之间存在重叠；而尿次黄嘌呤/肌酐摩尔浓度比值则不存在这种重叠。
