Abstract
Hereditary hypouricemia is generally caused by renal hypouricemia, an autosomal recessive disorder that is characterized by impaired renal tubular uric acid transport, or by xanthinuria, a rare autosomal recessive disorder caused by a deficiency of xanthine dehydrogenase (XDH; xanthinuria type I) or by a deficiency of both XDH and aldehyde oxidase (xanthinuria type II). In contrast to renal hypouricemia, which sometimes leads to exercise-induced acute kidney injury (EIAKI), xanthinuria has not been associated with this disorder. We report here a case of xanthinuria type I due to a compound heterozygous mutation. A 46-year-old woman was found to have undetectable plasma and urinary levels of uric acid. She had no symptoms and no history of EIAKI. Xanthinuria type I was diagnosed following the allopurinol loading test. Mutation analysis revealed a compound heterozygous mutation [c.305A>G (p.Gln102Arg) and c.2567delC (p.Thr856Lysfs*73)] in the XDH gene. Of these two mutations, the former is novel. The patient did not exhibit EIAKI. However, because xanthinuria is a rare disease, the identification of additional cases is necessary to determine whether this disease is complicated with EIAKI.
Similar content being viewed by others
References
Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha SH, Hosoyamada M, Takeda M, Sekine T, Igarashi T, Matsuo H, Kikuchi Y, Oda T, Ichida K, Hosoya T, Shimokata K, Niwa T, Kanai Y, Endou H. Molecular identification of a renal urate anion exchanger that regulates blood urate levels. Nature. 2002;417:447–52.
Li S, Sanna S, Maschio A, Busonero F, Usala G, Mulas A, Lai S, Dei M, Orrù M, Albai G, Bandinelli S, Schlessinger D, Lakatta E, Scuteri A, Najjar SS, Guralnik J, Naitza S, Crisponi L, Cao A, Abecasis G, Ferrucci L, Uda M, Chen WM, Nagaraja R. The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts. PLoS Genet. 2007;3:e194.
Ichida K, Hosoyamada M, Hisatome I, Enomoto A, Hikita M, Endou H, Hosoya T. Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion. J Am Soc Nephrol. 2004;15:164–73.
Kojima T, Nishina T, Kitamura M, Hosoya T, Nishioka K. Biochemical studies on the purine metabolism of four cases with hereditary xanthinuria. Clin Chim Acta. 1984;137:189–98.
Ichida K, Amaya Y, Okamoto K, Nishino T. Mutations associated with functional disorder of xanthine oxidoreductase and hereditary xanthinuria in humans. Int J Mol Sci. 2012;13:15475–95.
Ichida K, Amaya Y, Kamatani N, Nishino T, Hosoya T, Sakai O. Identification of two mutations in human xanthine dehydrogenase gene responsible for classical type Ixanthinuria. J Clin Invest. 1997;99:2391–7.
Ichida K, Matsumura T, Sakuma R, Hosoya T, Nishino T. Mutation of human molybdenum cofactor sulfurase gene is responsible for classical xanthinuria type II. Biochem Biophys Res Commun. 2001;282:1194–200.
Boulieu R, Bory C, Baltassat P, Gonnet C. Hypoxanthine and xanthine levels determined by high-performance liquid chromatography in plasma, erythrocyte, and urine samples from healthy subjects: the problem of hypoxanthine level evolution as a function of time. Anal Biochem. 1983;129:398–404.
Ichida K, Yoshida M, Sakuma R, Hosoya T. Two siblings with classical xanthinuria type 1: significance of allopurinol loading test. Intern Med. 1998;37:77–82.
Ichida K, Amaya Y, Noda K, Minoshima S, Hosoya T, Sakai O, Shimizu N, Nishino T. Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): structural analysis of the protein and chromosomal location of the gene. Gene. 1993;133:279–84.
Amaya Y, Yamazaki K, Sato M, Noda K, Nishino T, Nishino T. Proteolytic conversion of xanthine dehydrogenase from the NAD-dependent type to the O2-dependent type. Amino acid sequence of rat liver xanthine dehydrogenase and identification of the cleavage sites of the enzyme protein during irreversible conversion by trypsin. J Biol Chem. 1990;265:14170–5.
Nakamura M, Yuichiro Y, Sass JO, Tomohiro M, Schwab KO, Takeshi N, Tatsuo H, Ichida K. Identification of a xanthinuria type I case with mutations of xanthine dehydrogenase in an Afghan child. Clin Chim Acta. 2012;414:158–60.
Sakamoto N, Yamamoto T, Moriwaki Y, Teranishi T, Toyoda M, Onishi Y, Kuroda S, Sakaguchi K, Fujisawa T, Maeda M, Hada T. Identification of a new point mutation in the human xanthine dehydrogenase gene responsible for a case of classical type I xanthinuria. Hum Genet. 2001;108:279–83.
Jurecka A, Stiburkova B, Krijt J, Gradowska W, Tylki-Szymanska A. Xanthine dehydrogenase deficiency with novel sequence variations presenting as rheumatoid arthritis in a 78-year-old patient. J Inherit Metab Dis. 2010;33(Suppl 3):S21–4.
Stiburkova B, Krijt J, Vyletal P, Bartl J, Gerhatova E, Korinek M, Sebesta I. Novel mutations in xanthine dehydrogenase/oxidase cause severe hypouricemia: biochemical and molecular genetic analysis in two Czech families with xanthinuria type I. Clin Chim Acta. 2012;413:93–9.
Levartovsky D, Lagziel A, Sperling O, Liberman U, Yaron M, Hosoya T, Ichida K, Peretz H. XDH gene mutation is the underlying cause of classical xanthinuria: a second report. Kidney Int. 2000;57:2215–20.
Kudo M, Moteki T, Sasaki T, Konno Y, Ujiie S, Onose A, Mizugaki M, Ishikawa M, Hiratsuka M. Functional characterization of human xanthine oxidase allelic variants. Pharmacogenet Genomics. 2008;18:243–51.
Gok F, Ichida K, Topaloglu R. Mutational analysis of the xanthine dehydrogenase gene in a Turkish family with autosomal recessive classical xanthinuria. Nephrol Dial Transplant. 2003;18:2278–83.
Fujiwara Y, Kawakami Y, Shinohara Y, Ichida K. A case of hereditary xanthinuria type 1 accompanied by bilateral renal calculi. Intern Med. 2012;51:1879–84.
Arikyants N, Sarkissian A, Hesse A, Eggermann T, Leumann E, Steinmann B. Xanthinuria type I: a rare cause of urolithiasis. Pediatr Nephrol. 2007;22:310–4.
Ohta T, Sakano T, Ogawa T, Kato J, Awaya Y, Kihara H, Kinoshita Y. Exercise-induced acute renal failure with renal hypouricemia: a case report and a review of the literature. Clin Nephrol. 2002;58:313–6.
Ohta T, Sakano T, Igarashi T, Itami N, Ogawa T. ARF Associated with Renal Hypouricemia Research Group. Exercise-induced acute renal failure associated with renal hypouricaemia: results of a questionnaire-based survey in Japan. Nephrol Dial Transplant. 2004;19:1447–53.
Yeun JY, Hasbargen JA. Renal hypouricemia: prevention of exercise-induced acute renal failure and a review of the literature. Am J Kidney Dis. 1995;25(6):937–46.
Ishikawa I. Acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise in patients with or without renal hypouricemia. Nephron. 2002;91(4):559–70.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have declared that no conflict of interest exists.
About this article
Cite this article
Iguchi, A., Sato, T., Yamazaki, M. et al. A case of xanthinuria type I with a novel mutation in xanthine dehydrogenase. CEN Case Rep 5, 158–162 (2016). https://doi.org/10.1007/s13730-016-0216-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13730-016-0216-3