Xanthinuria

An inherited disorder of purine metabolism that can be asymptomatic or revealed clinically by renal manifestations. Characterized by the excretion of large amounts of xanthine in the urine and tendency to form xanthine stones.

Xanthine Oxidase Deficiency; Xanthic Urolithiasis; Xanthine Dehydrogenase Deficiency.

Not exactly known; estimated to be from 1:6000 to 1:60,000 live births. Proportion of each of the two types is 50%.

Autosomal recessive.

Deficiency of the enzyme xanthine oxidase, which mediates the oxidation of hypoxanthine to xanthine and of xanthine to uric acid. This leads to an increased urinary excretion of hypoxanthine and xanthine, with a tendency to form xanthine stones. Uric acid is strikingly diminished in the serum and urine. Two distinct forms of xanthinuria are recognized: type I (caused by mutations in the gene encoding xanthine dehydrogenase [XDH] located on 2p23-p22), with isolated deficiency of xanthine dehydrogenase; type II, with deficiency of xanthine dehydrogenase and aldehyde oxidase. Only type I patients can metabolize allopurinol. Additionally, xanthinuria occurs in molybdenum cofactor deficiency, where sulfite oxidase (SO) is also inactive.

Twenty percent of patients are asymptomatic. Symptoms are not specific. Irritability, vomiting, and failure to thrive may be the presenting symptoms. The patient may present at any age with hematuria, pyuria, renal colic, dysuria, urinary frequency, urine incontinence, polyuria, abdominal pain, or symptoms of a urinary tract infection. Laboratory findings include low or absent uric acid replaced by xanthine in concentrations from 10 to 40 μmol/L. Hypoxanthine concentrations are lower than 5 μmol/L. Xanthine and hypoxanthine can be find in the urine, xanthine calculi in the urinary tract, and crystalline deposits in skeletal muscles.

Xanthine stones may lead to renal colic, hematuria, voiding dysfunction, irritability, orange-red urinary sediment, hydronephrosis, and pyelonephritis. A unique type of myopathy is associated with crystalline deposits in skeletal muscles. Joint pain and muscle cramps or muscle pain are symptoms of the arthropathy and myopathy.

Adequate hydration must be ensured to minimize the urinary concentration of xanthine and hypoxanthine. Evaluate renal function (clinical, echography, laboratory including urea, creatinine, and electrolytes).

It is essential to maintain adequate hydration and intravascular volume. Succinylcholine should not be used in patients presenting with associated myopathy. Although there are no reports in the literature suggesting that there is an increased risk of hyperkalemia and/or malignant hyperthermia in these patients, the presence of severe muscle cramps may be enough to raise significant concern.

Succinylcholine is best avoided because of myopathy.

Molybdenum Cofactor Deficiency: Autosomal recessive; present in the neonatal period with microcephaly and central nervous system manifestations. It is caused by a congenital defect of a molybdenum-containing cofactor essential for the function of three distinct enzymes (xanthine dehydrogenase, aldehyde oxidase, sulfite oxidase). Generally lethal in the first year of life because of sulfite oxidase deficiency. Anesthetic implications of this form concern enflurane, which is best avoided ...