Xanthinuria

Xanthinuria literally means (excess) xanthines(purines) in urine.

Other Names

Xanthine dehydrogenase deficiency; XDH deficiency; Xanthine oxidase deficiency

Xanthine dehydrogenase

Types

Type I xanthinuria, a type of classical xanthinuria, is a rare autosomal recessive disorder of purine metabolism. Hereditary xanthinuria type II results from mutations in the MOCOS gene

Type I xanthinuria

It is caused by a genetic deficiency of xanthine dehydrogenase.

Pathophysiology

Hereditary xanthinuria type I is caused by mutations in the XDH gene. This gene provides instructions for making an enzyme called xanthine dehydrogenase.

Function of xanthine dehydrogenase

• Xanthine dehydrogenase is an enzyme is involved in the normal breakdown of purines, which are building blocks of DNA and its chemical cousin, RNA.
• Xanthine dehydrogenase carries out the final two steps in the process, including the conversion of xanthine to uric acid.
• Mutations in the XDH gene reduce or eliminate the activity of xanthine dehydrogenase.
• The enzyme is not available to help carry out the last two steps of purine breakdown.
• Because xanthine is not converted to uric acid, affected individuals have high levels of xanthine and very low levels of uric.

Hereditary xanthinuria type II

Hereditary xanthinuria type II results from mutations in the MOCOS gene. This gene provides instructions for making an enzyme called molybdenum cofactor sulfurase. This enzyme is necessary for the normal function of xanthine dehydrogenase, described above, and another enzyme called aldehyde oxidase. Mutations in the MOCOS gene prevent xanthine dehydrogenase and aldehyde oxidase from being turned on (activated) . The loss of xanthine dehydrogenase activity prevents the conversion of xanthine to uric acid, leading to an accumulation of xanthine in the kidneys and other tissues. The loss of aldehyde oxidase activity does not appear to cause any health problems.

Clinical features

It is characterized by the isolated deficiency of xanthine dehydrogenase, causing hyperxanthinemia with low or absent uric acid and xanthinuria, leading to urolithiasis, hematuria, renal colic and urinary tract infections, while some patients are asymptomatic and others suffer from kidney failure.

Less common manifestations include arthropathy, myopathy and duodenal ulcer.

Symptoms

• Hydronephrosis
• Hyperxanthinemia
• Myopathy
• Pyelonephritis
• Reduced xanthine dehydrogenase level
• Xanthine nephrolithiasis
• Xanthinuria

Inheritance

Autosomal recessive inheritance

Diagnosis

Reduced or absent uric acid, reduced xanthine dehydrogenase levels and genetic testing

Treatment

There is no specific treatment beyond maintaining a high fluid intake and avoiding foods that are high in purine.

NIH genetic and rare disease info

• NIH info on Xanthinuria

Xanthinuria is a rare disease.

Xanthinuria Resources
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