This report describes xanthinuria, type I (XAN1), which is inherited as an autosomal recessive and is caused by defects in the xanthine dehydrogenase (XDH) gene. XDH is a key enzyme in purine degradation; its loss results in accumulation of high levels xanthine. There is a single fly ortholog, Dmel\ry, for which (many!) classical amorphic and loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
The human XDH gene has not been introduced into flies.
Animals homozygous for a null mutation of Dmel\ry are viable on standard culture medium and exhibit a darkened eye color; they are sensitive to purine-supplemented medium. Genetic interactions of ry have been described; see the ry gene report.
[updated Apr. 2017 by FlyBase; FBrf0222196]
[XANTHINURIA, TYPE I; XAN1](https://omim.org/entry/278300)
[XANTHINE DEHYDROGENASE; XDH](https://omim.org/entry/607633)
Xanthinuria is characterized by high levels of xanthine and very low levels of uric acid in the blood and urine. The excess xanthine can accumulate in the kidneys and other tissues. In the kidneys, xanthine forms crystals that occasionally build up to create kidney stones; kidney stones can impair kidney function and ultimately cause kidney failure. Less commonly, xanthine crystals build up in the muscles, causing pain and cramping. [from Genetic Home Reference, Hereditary xanthinuria; 2015.12.21] Hypoxanthine does not accumulate to an appreciable degree because it is recycled through a salvage pathway (by HGPRT). [from Medscape, http://emedicine.medscape.com/article/984002-overview; 2015.12.21]
Xanthinuria is characterized by excretion of large amounts of xanthine in the urine and a tendency to form xanthine stones. [from MIM:278300; 2015.12.21]
Xanthinuria, type I, is inherited as an autosomal recessive. Several missense mutations and one frameshift mapped to the XDH gene have been associated with xanthinuria, type I. [from MIM:607633; 2015.12.21] In type I there is an isolated deficiency in xanthine dehydrogenase (XDH); in type II there is a dual deficiency of xanthine dehydrogenase and aldehyde oxidase (AOX1). [from MIM:278300; 2015.12.21]
XDH is a key enzyme in purine degradation. It catalyzes the oxidation of hypoxanthine to xanthine and the oxidation of xanthine to uric acid, and it contributes to the generation of reactive oxygen species.[from UniProt:P47989; 2015.12.21]
Xanthine dehydrogenase belongs to the group of molybdenum-containing hydroxylases involved in the oxidative metabolism of purines (Xu et al., 1996; pubmed:8661045). [from MIM:607633; 2015.12.21]
One to one: 1 human to 1 Drosophila.
Ortholog of human XDH (1 Drosophila to 1 human). Dmel\ry shares 52% identity and 69% similarity with human XDH.
