Introduction
Purines are components of the deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) genetic materials. The purines get metabolized by the enzyme xanthine oxidoreductase (XOR). It is the catalytic oxidation of hypoxanthine into xanthine and then xanthine and uric acid. Uric acid is more soluble and is excreted in the urine.
What Is Xanthine Oxidoreductase Deficiency?
A genetic metabolic deficiency of the enzymes “xanthine dehydrogenase," “xanthine oxidase," or “xanthine oxidoreductase” is called xanthine oxidoreductase deficiency or xanthinuria. There is an overproduction of hypoxanthine and xanthine. So, the excess is excreted in the urine. Uric acid production is decreased, so uric acid levels are lower, and xanthine levels are higher in the urine.
What Are the Types of Xanthinuria?
There are two types of Xanthinuria:
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Type 1 Xanthinuria - There is a deficiency of only one enzyme involved in purine metabolism: xanthine dehydrogenase.
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Type 2 Xanthinuria - There is a combined deficiency of two enzymes, xanthine dehydrogenase, and aldehyde oxidase, or it can be a combined deficiency of xanthine dehydrogenase, aldehyde oxidase, and sulfite oxidase (molybdenum cofactor).
What Causes A Deficiency of Xanthine Oxidoreductase?
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Type I hereditary xanthinuria is a genetic disease. Mutations in the xanthine dehydrogenase (XDH) gene causes it. This gene codes for the xanthine dehydrogenase enzyme, which is responsible for the catabolic metabolism of purines (one of the main component of DNA and RNA). This enzyme catalyzes the final steps of purine metabolism, where xanthine is converted into uric acid. As a result of enzyme deficiency, xanthine does not get converted into uric acid. So, there is excess xanthine present in the urine and blood of the affected individuals and decreased elimination of uric acid in urine.
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Type 2 hereditary xanthinuria is a genetic deficiency of the molybdenum cofactor sulfurase enzyme caused by mutations in the molybdenum cofactor sulfurase (MOCOS) gene. This gene controls the instructions while producing the molybdenum cofactor sulfurase enzyme, and is also essential for the enzyme xanthine dehydrogenase to get activated. It activates other enzyme called aldehyde oxidase. The loss of function of xanthine dehydrogenase affects the conversion of xanthine into uric acid. So, there is an accumulation of xanthine in urine and blood and a decrease in uric acid levels in urine. Usually, a deficiency of aldehyde oxidase does not have any effect on the human body and will not show any signs of deficiency.
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Sometimes a third type of xanthinuria exists where all forms of molybdenum cofactors are deficient, along with xanthine dehydrogenase and molybdenum cofactor sulfurase.
What Is the Inheritance Pattern of Xanthine Oxidoreductase Deficiency?
This disease has an autosomal recessive pattern of inheritance. This means the affected individuals will have two copies of the mutated genes from each parent. The parents are carriers of the mutated gene.
Parents who carry the altered gene will each have a 25 percent chance of having a child with two altered genes who are affected, a 50 percent chance of having a child with only one copy of the altered gene who will also be a carrier, and a 25 percent chance of having an unaffected child who will have two copies of healthy, unchanged genes.
What Are the Signs and Symptoms of Xanthinuria?
Affected individuals may be symptomatic or will not show any signs and symptoms.
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Xanthinuria: Presence of high levels of xanthine in the blood and urine.
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Hematuria: Presence of blood in the urine.
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Urolithiasis or Renal Calculi: Presence of kidney stones.
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Abdominal Pain: Pricking or throbbing kind of pain.
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Urinary Infections: Repeated urinary tract infections leading to permanent kidney damage..
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Myopathy: There is a deposition of crystalline substances in skeletal muscle, which causes muscle weakness and difficulty in movements.
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Renal Failure: Acute renal failure.
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A rare type of xanthinuria with a combined efficiency of xanthine dehydrogenase and all forms of molybdenum factors and also molybdenum cofactor sulfurase shows some serious signs and symptoms, like seizures and feeding difficulties in newborns, disturbance in muscle tone, dislocation of the ocular lens, severely impaired intellectual functioning, and early death in infants.
How Is Xanthinuria Diagnosed?
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Blood Test: There are low levels of uric acid, less than 1 milligram per deciliter, and high levels of xanthine.
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Urine Test: Hypouricemia is present, as evidenced by lower levels of uric acid in the urine.
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Ultrasonography: It is used to view the presence of stones in different body organs with the application of high-energy sound waves.
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Ultrasound: It is a technique that uses ultrasound echoes to visualize kidneys for stones by demarcating objects based on density.
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Allopurinol Loading Test: A load of allopurinol is given, and the plasma concentration of its metabolites is tested after one hour. The levels help identify disease.
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Molecular Analysis: A sample of tissue, blood, or any other body fluid is taken for testing different components like proteins, biological markers, genes, and other molecules.
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Xanthine Oxidase Assay: This test uses a sample of blood, plasma, or serum to determine the level of activity of xanthine oxidase activity.
How Is Xanthine Oxidoreductase Deficiency Treated?
Since it is a hereditary condition, this deficiency cannot be cured. The only effective treatment involves consuming a diet low in purines like eggs, nuts, peanut butter, fruits and fruit juices, dairy products low in fat (cheese, yogurt, skimmed milk), potatoes, bread, pasta, and rice.
Foods high in purines like red meat, duck, anchovies, sardines, herring, mussels, codfish, high-fat dairy products, and beer should be avoided. Affected people should drink plenty of water and fluids to prevent formation of stones in the kidneys. The symptoms can be managed by lifestyle changes. There are no specific drugs to treat the deficiency.
What Is the Prognosis of Patients With Xanthine Oxidoreductase Deficiency?
Most affected people have no or few symptoms, but only a few have end-stage kidney failure requiring kidney transplantation. The prognosis is favorable.
Conclusion:
Since it is a rare metabolic disease, not much information related to its cause or treatment is available. However scope for finding new treatment options for this metabolic disorder is there as further studies are underway. The affected patients should have regular tests for renal functions and other major systems of the body. Further advanced treatments are currently under research for the condition.
