Modern diagnostic approach to hereditary xanthinuria

Urolithiasis. 2015 Feb;43(1):61-7. doi: 10.1007/s00240-014-0734-4. Epub 2014 Nov 6.


Hereditary xanthinuria (HX) is a rare inherited disorder caused by a deficiency of xanthine dehydrogenase/oxidase (XDH/XO). Missing XDH/XO activity leads to undetectable levels of uric acid excessively replaced by xanthine in serum/urine. The allopurinol loading test has been traditionally used to differentiate between HX types I and II. Final confirmation of HX has been based on the biopsy finding of the absent XDH/XO activity in the small intestine or liver. We present the clinical, biochemical, ultrasound and molecular genetics findings in three new patients with HX and suggest a simple three-step approach to be used for diagnosis, typing and confirmation of HX. In the first step, the diagnosis of HX is determined by extremely low serum/urinary uric acid excessively replaced by xanthine. Second, HX is typed using urinary metabolomics. Finally, the results are confirmed by molecular genetics. We advocate for this safe and non-invasive diagnostic algorithm instead of the traditional allopurinol loading test and intestinal or liver biopsy used in the past.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol / metabolism
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Male
  • Metabolism, Inborn Errors / diagnosis*
  • Metabolomics
  • Uric Acid / blood
  • Uric Acid / urine
  • Xanthine Dehydrogenase / deficiency*


  • Uric Acid
  • Allopurinol
  • Xanthine Dehydrogenase

Supplementary concepts

  • Xanthinuria, Type I