Xanthinuria type I: a rare cause of urolithiasis

Xanthinuria type I is a rare disorder of purine metabolism caused by xanthine oxidoreductase or dehydrogenase (XDH) deficiency. We report a family with two affected children out of 335 pediatric stone patients studied since 1991 in Armenia. The propositus, a 13-month-old boy, presented with abdominal pain and urinary retention followed by stone passage (0.9x0.6 cm). Infrared spectroscopy in Yerevan revealed a pure xanthine stone. Family examination in the parents and brother was normal, but the propositus and his 8-year-old asymptomatic sister had hypouricemia, hypouricosuria, and high urinary excretion of hypoxanthine and xanthine. Ultrasonography in the index patient showed bilateral stones requiring pyelolithotomy. High fluid intake and purine restriction did not prevent further stone passages. The affected asymptomatic sister had a small pelvic stone (4 mm). Mutation analysis revealed a heterozygous novel base pair substitution in exon 25 of the XDH gene (c.2810C > T), resulting in an amino acid substitution (p.Thr910Met). The second mutation could not be detected. Despite this, the heterozygous mutation, the chemical findings, and the positive allopurinol test altogether prove xanthinuria type 1, which may present wide clinical intrafamilial variation. Diagnosis is suspected usually from low serum uric acid. No specific therapy is available.