Xanthinuria, the presence of increased quantities of xanthine in the urine, is a genetic disorder characterized by a deficiency of the enzymes involved in purine metabolism, thereby leading to excessive accumulation of xanthine in the body.
Xanthinuria is a hereditary disease with two major forms- types I and II. Both forms show an autosomal recessive mode of inheritance and are differentiated by the purine metabolism enzyme that is deficient. The enzyme xanthine dehydrogenase is deficient in type I xanthinuria while a dual deficiency of xanthine dehydrogenase and aldehyde oxidase occurs in type II xanthinuria. The third type of xanthinuria, associated with molybdenum cofactor deficiency, has been described as a separate clinical entity due to the neurological involvement. In addition, iatrogenic xanthinuria may be rarely observed in patients treated with allopurinol during the course of aggressive chemotherapy [1] [2].
There is no difference in the clinical presentations of xanthinuria type I and type II. The enzyme deficiencies which are seen in xanthinuria prevent the transformation of hypoxanthine to xanthine and xanthine to uric acid. There is a salvage pathway for hypoxanthine, while a similar pathway for xanthine does not exist. Consequently, the xanthine accumulates and is excreted in the urine. Furthermore, excessive xanthine accumulates mostly within the kidneys, leading to nephropathy and urolithiasis, making the kidneys more prone to infections. Renal failure is the most severe consequence of xanthinuria [3] [4] [5].
Symptoms in patients with xanthinuria mimic the symptoms seen in any other condition presenting with the stone formation or urinary infection. Renal colic, dysuria, nocturia, polyuria, microscopic or macroscopic hematuria, and pyuria may be commonly observed in such patients.
Other less common sites of xanthine deposits are the muscles and the joints. Myopathy mainly occurs in older patients and results in muscle cramps and pain. The involvement of the joints clinically results in joint pain and stiffness [6].
Non-specific symptoms such as abdominal pain, nausea, vomiting, and irritability may be present in young children. Some pediatric patients may have growth retardation as a consequence of xanthinuria. However, two-thirds of patients may not have any symptoms at all and the disease is revealed accidentally [6] [7].
Xanthinuria is a rare cause of renal disease and other more common disorders must be ruled out first. However, if the diagnosis is suspected, it can be confirmed through laboratory and imaging techniques.
Urinalysis may reveal the presence of xanthine crystals along with other findings suggestive of kidney damage such as hematuria and pyuria. The levels of uric acid are extremely low. The 24-hour urine levels of xanthine and hypoxanthine, on the other hand, are significantly high. A urine culture may detect the microorganisms responsible for superadded infection [8].
Changes in serum chemistry are analogous to those seen in the urine. A low serum uric acid, coupled with increased levels of xanthine and hypoxanthine are usually seen. Other causes of a low serum uric acid should be considered while making a diagnosis of xanthinuria.
Imaging studies help support the diagnosis. Ultrasonography may detect stones larger than 1 cm in diameter. Xanthine stones are radiolucent and cannot be revealed via an X-ray. Computed tomography (CT) or magnetic resonance imaging (MRI) scans are recommended for patients presenting with the typical clinical features of nephrolithiasis but with a negative result on ultrasonography [9]. Histology may reveal renal parenchymal xanthine deposits, thereby leading to renal damage and fibrosis.