Xanthinuria – Causes, Symptoms and Treatment

What is Xanthinuria?

Xanthinuria is a rare inherited or acquired metabolic disorder in which the compound xanthine – a breakdown product of purine metabolism – cannot be adequately processed and therefore accumulates in the blood and urine. Under normal circumstances, xanthine is converted to uric acid by the enzyme xanthine oxidase. In xanthinuria, this enzyme is defective or completely absent.

Causes

There are two main forms of xanthinuria:

• Type I (classical xanthinuria): Caused by an inherited deficiency of xanthine oxidase due to a mutation in the XDH gene. The condition follows an autosomal recessive inheritance pattern.
• Type II (combined molybdenum cofactor deficiency): In addition to xanthine oxidase, the enzyme aldehyde oxidase is also absent, resulting from a defect in the shared cofactor molybdopterin.
• Acquired form: Secondary xanthinuria can be triggered by treatment with allopurinol, a xanthine oxidase inhibitor used in the management of gout.

Symptoms

Many individuals with xanthinuria are asymptomatic and the condition is discovered incidentally. Possible symptoms include:

• Kidney stones (xanthine stones): The most common clinical complication, as xanthine is poorly soluble in urine and tends to crystallize.
• Muscle problems (myopathy): Pain and weakness in muscles due to xanthine crystal deposits.
• Joint inflammation (arthropathy): Similar to gout, xanthine crystals can deposit in the joints.
• Renal impairment: Repeated stone formation may permanently compromise kidney function in severe cases.
• In Type II, additional neurological abnormalities may be present.

Diagnosis

Xanthinuria is diagnosed through a combination of tests:

• Urine analysis: Detection of elevated xanthine concentrations and reduced uric acid levels in urine.
• Blood tests: Low serum uric acid levels (hypouricaemia).
• Enzyme activity assay: Measurement of xanthine oxidase activity in a biopsy sample (e.g., from the intestinal mucosa or liver).
• Genetic testing: Molecular genetic identification of the causative mutation in the XDH gene.
• Imaging: Ultrasound or X-ray to detect kidney stones.

Treatment

There is currently no curative therapy available. Treatment focuses on preventing complications:

• High fluid intake: Drinking plenty of fluids (at least 2–3 litres per day) dilutes the urine and reduces crystal formation.
• Low-purine diet: Reducing purine-rich foods (e.g., meat, organ meats, legumes) decreases xanthine production.
• Urine alkalinisation: Sodium bicarbonate or potassium citrate can raise urinary pH and improve xanthine solubility.
• Treatment of kidney stones: Depending on size and location, conservative management, lithotripsy (shock wave therapy), or surgical procedures may be required.
• In the acquired form (allopurinol-induced), dose adjustment of the medication may be necessary.

References

1. Reiter S. et al. - Xanthinuria type I: a rare but important differential diagnosis of renal calculi. Nephrology Dialysis Transplantation, 2010.
2. Orphanet – Xanthinuria. Online database for rare diseases. www.orpha.net (accessed 2024).
3. Scriver C.R. et al. (eds.) - The Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill, 8th edition, 2001.