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1. The metabolic fate of high dietary intakes of nicotinamide, nicotinic acid and tryptophan, and of acute doses of nicotinamide and nicotinic acid, has been studied in the rat. A new high-pressure liquid chromatography method for measurement of the principal urinary metabolites of niacin is described.2. Administration to rats of a single oral dose of nicotinamide or nicotinic acid (up to 100 mg/kg body-weight), or maintenance for 3 weeks on diets providing 150 mg nicotinamide or nicotinic acid/kg diet, resulted in only a small increase in the liver content of nicotinamide nucleotide coenzymes (NAD and NADP). The quantitative metabolism of nicotinamide and nicotinic acid differed, suggesting that intestinal bacterial deamidation is not the major fate of nicotinamide.3. A high dietary intake of tryptophan (5.9 g/kg diet) led to a considerable increase in liver NAD(P) and also in urinary excretion of niacin metabolites. The results suggest that, as indicated by enzyme kinetic studies (Bender et al. 1982), the utilization of nicotinamide and nicotinic acid for nucleotide synthesis is limited, while there is little or no limitation of NAD(P) synthesis from the tryptophan metabolite quinolinic acid.

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In hypoxanthine (guanine) phosphoribosyltransferase- (HPRT; EC 2.4.2.8) deficient lymphoblasts, ATP but not nicotinamide-adenine dinucleotide coenzyme concentrations are reduced by limited nutrition. Such reduced ATP concentrations are correlated with reduced poly(ADP-ribose) synthetase (polyADPRT; EC 2.4.2.30) activity; this reduces the breakdown of nicotinamide-adenine dinucleotide coenzymes and thus explains their normal intracellular concentrations. Since reductions in poly(ADP-ribose) synthetase activity reduce DNA repair, alterations in DNA could accumulate even in non-multiplying cells such as neurons, especially in the continuously active 'respiratory centre'. Our Lesch-Nyhan patients suffered respiratory deaths between 15 and 20 years of age.

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.

director 4 , Michael Machesney chair 5 , Colin Rees vice president (chair of endoscopy) 2 , Stephen P Halloran member, bowel screening advisory committee 6 , Muti Abulafi chair 7 , Deborah Alsina chief executive 8

Our patient was found to be hypouricaemic, 31/~molL -a (normal 100-425/lmolL -1) during a survey of 1000 consecutive pregnant women. At 16 weeks (w) gestation her urinary urate was low, 0.3mmo124h -1 (normal 2.1-4.4mmo124h -1) and plasma xanthine (xan) was high at 9/~molL -1 (normal <2/imol L-i), confirming a diagnosis of xanthine oxidase deficiency (McKusick 27830). Normal pregnancy ended in the spontaneous onset of labour at 41w, and a normal vaginal delivery of a fit 3.39 kg girl who was breastfed.Maternal plasma urate (/~mol L -1) rose to 47 at 27w, 54 at 31w and 120 in labour at 41w, and fell after delivery to 25-35. Maternal plasma xan concentrations (/lmolL -i) rose slightly in pregnancy from 9 at 16w to 12 at 31w and returned to 10 six weeks after delivery. In the 2 days after delivery xan concentrations fell from 30 to 23. Plasma hypoxanthine (hyp) concentrations (/~mol L -~) were at the upper limits of the normal range, being 4 at 16w and 5 at 31W. Labour markedly raised concentrations of hyp to 20 and of xan to 21; the hyp elevation is greater than the normal approximate doubling of concentration during labour to a mean (SD) 3.5 (1.6), n = 12. Six weeks after delivery plasma hyp had returned to a normal value of 3.After delivery the mixed cord blood (fetal) concentrations (/lmol L -i) of hyp were 25 (normal <10) and ofxan were 7 (normal <4). Amniotic fluid concentrations (/~molL -i) of hyp were 11 and of xan were 14 (normal after labour <10)o Maternal renal excretion of xan (nmol per h per kg body weight) rose from 580 at 16w to 1020 at 31w and 990 at 41w, falling to 490 six weeks after delivery with no systematic change in hyp excretion (107-180 nmol per h per kg body weight). Maternal weight was 73.5kg. Hyp would be efficiently recycled by the mother despite her inability to metabolize xan. No rise in urinary excretion of urate was detected. Calculated renal clearances for hyp and xan were similar to previous values (Harkness et al., 1983) although creatinine outputs were low. The minimal urinary excretion values suggest a transfer of purines hyp and xan from fetus to mother throughout the last 3 months of pregnancy. The rises in plasma urate are also consistent with such a transfer of urate and agree with previous results in 4 pregnancies (Uzan et al., 1980, Simmonds et aI., 1982.The fetus and infant had normal xanthine oxidase activity since urate concentrations (/lmolL -~) of 204 in amniotic fluid (normal range 200-520), and of 192 in cord blood plasma were normal and were higher than the urate concentration of 120 in maternal blood plasma at delivery; in addition, the infant's excretions (nmol per h per kg body weight) of hyp, 8, and xan, 10, were normal. However, fetal (cord) blood plasma concentrations of hyp and of xan were more than twice the 1Division

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