Xanthinuria

At a glance

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 and severe hypouricemia.

Synonyms

Xanthine Oxidoreductase Deficiency; Xanthic Urolithiasis; Xanthine Dehydrogenase Deficiency.

Incidence

First reported in 1954; estimated incidence between 1:6,000 and 1:60,000 live births with equal proportion of Type I and Type II.

Genetic inheritance

Autosomal recessive.

Pathophysiology

Deficiency of the enzyme xanthine oxidoreductase, which catalyzes the hydroxylation 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 oxidoreductase [XOR] located on 2p23-p22), with isolated deficiency of xanthine oxidoreductase; Type II (caused by mutation of human MoCo sulfurase gene), with deficiency of xanthine oxidoreductase and aldehyde oxidase. Xanthinuria occurs in molybdenum cofactor deficiency, where sulfite oxidase (SO) is also inactive in addition to xanthine oxidoreductase and aldehyde oxidase.

Diagnosis

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 found in the urine, xanthine calculi in the urinary tract, and crystalline deposits in skeletal muscles.

Clinical aspects

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

Precautions before anesthesia

There are no specific reports relating to anesthesia. 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).

Anesthetic considerations

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

Pharmacological ...