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Lesch‐Nyhan syndrome and its pathogenesis: Purine concentrations in plasma and urine with metabolite profiles in CSF
Author(s) -
Harkness R. A.,
McCreanor G. M.,
Watts R. W. E.
Publication year - 1988
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf01800365
Subject(s) - hypoxanthine , hypoxanthine guanine phosphoribosyltransferase , lesch–nyhan syndrome , allopurinol , xanthine , hypoxanthine phosphoribosyltransferase , purine , endocrinology , urinary system , medicine , creatinine , uric acid , urine , purine metabolism , chemistry , metabolite , renal function , adenine phosphoribosyltransferase , excretion , biochemistry , enzyme , biology , mutant , gene
Summary 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.