title: Modern diagnostic approach to hereditary xanthinuria.
abstract: 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.
authors.affiliation: Department of Nephrology, Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Mraz
authors.forename: Olha
authors.initials: O
authors.lastname: Hurba
authors.forename: Josef
authors.initials: J
authors.lastname: Bartl
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Dolezel
authors.forename: Anthony
authors.initials: A
authors.lastname: Marinaki
authors.forename: Lynette
authors.initials: L
authors.lastname: Fairbanks
authors.forename: Blanka
authors.initials: B
authors.lastname: Stiburkova
mesh_terms: D000493:Allopurinol / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis*; D055432:Metabolomics; D014527:Uric Acid / Q000097:blood / Q000652:urine; D014968:Xanthine Dehydrogenase / Q000172:deficiency*
chemical_list: D014527:Uric Acid; D000493:Allopurinol; D014968:Xanthine Dehydrogenase