Pregnancy in and incidence of xanthine oxidase deficiency

Abstract

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

Molybdenum in Human Health and Disease

“…Type I xanthinuria patients carry mutations in the XDH gene [ 23 ]; up to date only a handful cases have been genetically classifi ed. The combined incidence for classical type I and type II xanthinuria has been estimated to 1/69,000 [ 24 ].…”

A Case of Hereditary Xanthinuria Type 1 Accompanied by Bilateral Renal Calculi

“…Classical xanthinuria has recently been classified into two subtypes (4,5). Type 1 lacks only xanthine dehydrogenase activity and is characterized by hypouricemia accompanying xanthine dehydrogenase deficiency, while type 2 lacks both xanthine dehydrogenase and aldehyde oxidase activity.…”

Identification of two mutations in human xanthine dehydrogenase gene responsible for classical type I xanthinuria.

“…Classical xanthinuria types I and II are rare autosomal recessive disorders and the combined incidence has been reported to be 1/69,000 (5). The affected individuals may develop urinary tract calculi, acute renal failure, or myositis due to tissue deposition of xanthine, but some subjects with homozygous xanthinuria remain asymptomatic (2).…”