Hereditary xanthinuria
Hereditary xanthinuria is a rare genetic condition characterized by high levels of xanthine and low levels of uric acid, which can lead to the formation of kidney stones, muscle pain, and potential kidney failure.
Overview
Hereditary xanthinuria is a condition that most often affects the kidneys. It is characterized by high levels of a compound called xanthine and very low levels of another compound called uric acid in the blood and urine. The excess xanthine can accumulate in the kidneys and other tissues. In some people with hereditary xanthinuria, the condition does not cause any health problems.
Symptoms
When the condition does cause symptoms, they are typically related to the accumulation of xanthine in body tissues:
- Kidney Issues: In the kidneys, xanthine forms tiny crystals that occasionally build up to create kidney stones. These stones can impair kidney function and ultimately cause kidney failure. Related signs and symptoms can include abdominal pain, recurrent urinary tract infections, and blood in the urine (hematuria).
- Muscle Issues: Less commonly, xanthine crystals build up in the muscles, causing pain and cramping.
Types of Hereditary Xanthinuria
Researchers have described two major forms of this condition, which share the same signs and symptoms but are distinguished by the specific enzymes involved:
- Type I: Distinguished by the specific loss of the enzyme xanthine dehydrogenase.
- Type II: Distinguished by the loss of both xanthine dehydrogenase and aldehyde oxidase activity.
Frequency
The combined incidence of hereditary xanthinuria types I and II is estimated to be about 1 in 69,000 people worldwide. However, researchers suspect that the true incidence may be higher because some affected individuals have no symptoms and are never diagnosed. The condition appears to be more common in people of Mediterranean or Middle Eastern ancestry. About 150 cases have been reported in the medical literature.
Causes
Hereditary xanthinuria is caused by genetic mutations that disrupt the normal breakdown of purines, which are building blocks of DNA and RNA:
- Hereditary xanthinuria type I is caused by mutations in the XDH gene. This gene provides instructions for making an enzyme called xanthine dehydrogenase. This enzyme carries out the final two steps in the purine breakdown process, including the conversion of xanthine to uric acid (which is excreted in urine and feces). Mutations reduce or eliminate the activity of this enzyme, preventing the conversion of xanthine to uric acid and leading to high levels of xanthine and very low levels of uric acid in the blood and urine.
- 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 both xanthine dehydrogenase and another enzyme called aldehyde oxidase. Mutations prevent these enzymes from being activated. The loss of xanthine dehydrogenase activity leads to the accumulation of xanthine, while the loss of aldehyde oxidase activity does not appear to cause any health problems.
Inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- Combined deficiency of xanthine dehydrogenase and aldehyde oxidase
- Xanthine dehydrogenase deficiency
- Xanthine oxidase deficiency
- Xanthinuria
- XDH deficiency