Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


Xanthinuria hereditary (Hereditary Xanthinuria) - Genes XDH and snot.

Hereditary xanthinuria is a disease that most often affects the kidneys, characterized by high concentrations of xanthine and very low concentrations of uric acid in the blood and urine. Xanthine excess can accumulate in the kidneys and other tissues. Kidney, xanthine form small crystals that occasionally lead to kidney stones. These calculations can impair kidney function and eventually cause kidney failure. Some signs and symptoms related may include abdominal pain, recurrent urinary tract infections and hematuria. Less often, xanthine crystals accumulate in the muscles, causing pain and cramps. In some people with hereditary xanthinuria, the disease does not cause any health problems.

They described two main forms of hereditary xanthinuria, designated as types I and II. The types are distinguished by the enzymes involved, although they have the same signs and symptoms.

Xanthinuria hereditary type I is caused by mutations in the XDH gene, located on the short arm of chromosome 2 (2p23.1). This gene encodes xanthine dehydrogenase enzyme involved in normal breakdown of purines. Specifically, xanthine dehydrogenase carries out the final two steps in the process, including the conversion of hypoxanthine to xanthine and xanthine conversion into uric acid, which is excreted in urine and feces. In addition, it is believed that the xanthine dehydrogenase may be involved in the production of superoxide radicals. Specifically, xanthine dehydrogenase becomes sometimes otherwise called xanthine oxidase which produces superoxide radicals. These molecules are byproducts of normal cellular processes, and must be broken down regularly to prevent cell damage. It is believed that the superoxide radicals play a role in many diseases, including hypertension diseases. Have identified at least 12 XDH gene mutations cause hereditary xanthinuria as type I. XDH gene mutations reduce or eliminate the activity of xanthine dehydrogenase. As a result, the enzyme is not available to help carry out the final two stages of the breakdown of purines. Because no xanthine into uric acid, affected individuals have high levels of xanthine and very low concentrations of uric acid in the blood and urine. Xanthine excess can cause damage to the kidneys and other tissues.

Xanthinuria hereditary type II is due to mutations in the gene snot, located on the long arm of chromosome 18 (18q12). This gene encodes the enzyme cofactor sulfurase molybdenum. This enzyme is required for normal function of xanthine dehydrogenase, described above, and another enzyme called aldehyde oxidase. They have identified at least four mutations in the gene responsible for hereditary xanthinuria type II. Mutations in the gene Moços prevent xanthine dehydrogenase and aldehyde oxidase are activated. The loss of activity of xanthine dehydrogenase inhibits the conversion of xanthine into uric acid, leading to an accumulation of xanthine kidney and other tissues. Loss of aldehyde oxidase activity does not appear to cause health problems.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with hereditary xanthinuria, by complete PCR amplification of the exons of the XDH and snot, respectively, and subsequent sequencing genes.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).