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Prevalence of hereditary xanthinuria is not known, but about 150 patients have been described so far. Annual incidence has been estimated to be between 1:6,000 and 1:69,000. These rough estimates are due to the high rate of asymptomatic cases leading to underdiagnosis and the lack of newborn screening.

Symptom onset may be at any age. Approximately 50 % of the patients with classical hereditary xanthinuria present with symptoms of urinary tract infection, hematuria, renal colic, acute renal failure, crystalluria or urolithiasis. In some rare patients, renal disease may evolve to renal failure, or may even induce arthropathy, myopathy or duodenal ulcer.

Hereditary xanthinuria is due to mutations in the xanthine dehydrogenase (XDH, 2p23.1) or molybdenum cofactor sulfurase (MOCOS, 18q12.2) genes, resulting in failure to degrade hypoxanthine and xanthine to uric acid and leading to the accumulation of xanthine and, to a lesser extent, of hypoxanthine. Classical hereditary xanthinuria encompasses xanthinuria type I and II: type I is a simple xanthine dehydrogenase/oxidase deficiency, due to mutations in XDH, whereas type II results from a combined deficiency of xanthine dehydrogenase and aldehyde oxidase, due to mutations in MOCOS. Both enzymatic deficiencies lead to an identical clinical phenotype.

Diagnosis is based on estimation of uric acid in blood and urine. If hypouricemia is confirmed, detailed purine metabolic investigation follows, and includes measurement of xanthine and hypoxanthine in urine and plasma. High urinary levels of xanthine are then typical for classical hereditary xanthinuria. In about half of patients, ultrasonography reveals the presence of xanthine urolithiasis. Additional methods for diagnostic confirmation and/or identification of the type of xanthinuria include allopurinol loading test, xanthine oxidase assay and molecular analysis.

Hereditary xanthinuria is a clinical feature of molybdenum cofactor deficiency (see this term). The clinical picture of this disease is however much more severe, given the associated neurological damage and frequent infant death. Hypouricemia is also a biochemical marker for primary hereditary renal hypouricemia (see this term). Unlike hereditary xanthinuria, the excretion fraction of uric acid is elevated in renal hypouricemia.

Hereditary xanthinuria is an autosomal recessive disease, with a subsequent 25% recurrence risk.

There is no curative treatment. Low purine diet and high fluid intake is recommended. Since the solubility of xanthine is not affected by urinary pH, alkalization is of no value. When calculi are present, a pyelolithotomy might be necessary.

The overall prognosis is favorable, even though, in some cases, the disease progresses to end-stage renal insufficiency.