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 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%.
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
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,
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 ...