Novel mutations in xanthine dehydrogenase/oxidase cause severe hypouricemia: biochemical and molecular genetic analysis in two Czech families with xanthinuria type I.

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The article describes the clinical , biochemical , enzymological and molecular genetics findings in two patients from two families with xanthinuria type I .Biochemical analysis using high performance liquid chromatography , allopurinol loading test and analysis of xanthine oxidase activity in plasma and of uromodulin excretion in urine were performed . Sequencing analysis of the xanthine dehydrogenase gene and the haplotype and statistical analyses of consanguinity were performed .Probands showed extremely low concentrations of uric acid , on seven occasions under the limit of detection . The concentration of uric acid in 38 -year -old female was 15 μmol /L in serum and 0 .04 mmol /L in urine . Excretion of xanthine in urine was 170 mmol /mol creatinine . The concentration of uric acid in 25 -year -old male was 0 .03 mmol /L in urine . Excretion of xanthine in urine was 141 mmol /mol creatinine . The allopurinol loading test confirmed xanthinuria type I . The xanthine oxidase activities in patients were 0 and 0 .4 pmol /h /mL of plasma . We found three nonsense changes : p .P 214 QfsX 4 and unpublished p .R 825 X and p .R 881 X .We found two nonconsanguineous compound heterozygotes with xanthinuria type I caused by three nonsense changes . The methods used did not confirm consanguinity in the probands , thus there might be an unconfirmed biological relationship or mutational hotspot .