Hereditary xanthinuria

Hereditary xanthinuria is a rare inborn error of purine metabolism characterized by a deficiency of the enzyme xanthine dehydrogenase (also called xanthine oxidase), which is responsible for converting hypoxanthine to xanthine and xanthine to uric acid. This deficiency leads to very low or undetectable levels of uric acid in the blood and urine, with a corresponding accumulation of xanthine and, in some cases, hypoxanthine. There are two main types: Type I (classical xanthinuria), caused by an isolated deficiency of xanthine dehydrogenase due to mutations in the XDH gene, and Type II, caused by a dual deficiency of xanthine dehydrogenase and aldehyde oxidase due to mutations in the MOCOS gene (molybdenum cofactor sulfurase). A third form, molybdenum cofactor deficiency, involves xanthine dehydrogenase deficiency along with sulfite oxidase deficiency and presents with severe neurological impairment. The condition primarily affects the urinary system. Approximately one-third of affected individuals develop xanthine urolithiasis (kidney stones composed of xanthine), which can cause renal colic, hematuria, urinary tract infections, and in severe cases, obstructive uropathy or renal failure. Some patients may also develop xanthine deposits in muscles, leading to myopathy with muscle pain and cramps. However, many individuals with hereditary xanthinuria remain completely asymptomatic throughout life and are diagnosed incidentally through the finding of very low serum uric acid levels (hypouricemia). There is no specific cure for hereditary xanthinuria. Management focuses on prevention of xanthine stone formation through high fluid intake to maintain dilute urine and dietary restriction of purine-rich foods (such as organ meats, certain fish, and legumes) to reduce xanthine production. Allopurinol, which is commonly used for gout, is contraindicated as it inhibits xanthine oxidase and would further increase xanthine accumulation. Prognosis is generally favorable, especially with appropriate preventive measures, and many patients lead normal lives.

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