Summary about Disease
Xanthine dehydrogenase deficiency (Xanthinuria) is a rare genetic disorder characterized by a deficiency in the enzyme xanthine dehydrogenase. This enzyme is crucial for the breakdown of purines, which are building blocks of DNA and RNA. Its deficiency leads to an accumulation of xanthine in the blood and urine, and may result in the formation of xanthine crystals, potentially causing kidney problems. There are two main types: Type I, where xanthine dehydrogenase alone is deficient, and Type II, where both xanthine dehydrogenase and aldehyde oxidase are deficient. A third type has also been described related to molybdenum cofactor deficiency (the cofactor is required by both xanthine dehydrogenase and aldehyde oxidase).
Symptoms
Many individuals with xanthinuria are asymptomatic. When symptoms do occur, they can include:
Hematuria: Blood in the urine
Renal Colic: Severe pain caused by kidney stones
Xanthine Crystals in Urine: Presence of xanthine crystals during urination
Urinary Tract Infections: Increased susceptibility to infections
Kidney Stones (Xanthine): Formation of stones composed of xanthine
Muscle pain (rare): can occur after exercise.
Arthritis (rare)
Causes
Xanthinuria is caused by mutations in the XDH gene (for Type I) or the *MOCOS* gene (for Type II). These genes provide instructions for making xanthine dehydrogenase and molybdopterin synthase cofactor, respectively. The condition is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for their child to be affected. Molybdenum cofactor deficiency can also cause secondary xanthinuria.
Medicine Used
There is no specific medication to replace the deficient enzyme. Treatment focuses on managing symptoms and preventing complications. Common approaches include:
Allopurinol: This medication, paradoxically, is typically avoided in xanthinuria as it inhibits xanthine oxidase, the enzyme that converts xanthine to uric acid. While effective in other conditions, it could increase xanthine buildup in this case.
Alkaline Citrate (Potassium Citrate/Sodium Citrate): Used to increase urine pH, making xanthine more soluble and reducing the risk of crystal formation.
Increased Fluid Intake: To dilute urine and help flush out xanthine.
Is Communicable
No, xanthinuria is not a communicable disease. It is a genetic disorder inherited from parents. It cannot be transmitted from person to person through any infectious means.
Precautions
Precautions for individuals with xanthinuria focus on managing their diet and lifestyle to minimize xanthine accumulation and prevent kidney stone formation. These include:
High Fluid Intake: Drink plenty of water throughout the day.
Dietary Modifications: May require restriction of purine-rich foods (such as organ meats, seafood, and some legumes) in some individuals, but severe restriction is generally not necessary.
Regular Monitoring: Regular urine and kidney function tests to monitor xanthine levels and detect any complications early.
Avoid Dehydration: Dehydration can increase the risk of xanthine crystal formation.
Consultation with a Nephrologist: Work closely with a kidney specialist to manage the condition.
How long does an outbreak last?
Xanthinuria is a chronic, lifelong condition. There are no outbreaks in the traditional sense. Symptoms, such as renal colic from a kidney stone, may occur intermittently and last for hours to days until the stone passes or is treated. The underlying condition persists indefinitely.
How is it diagnosed?
Diagnosis typically involves:
Urine Analysis: Detecting elevated xanthine levels and/or xanthine crystals in the urine.
Blood Tests: To measure xanthine and uric acid levels.
Enzyme Assay: Measurement of xanthine dehydrogenase activity in a liver or intestinal biopsy (rarely performed).
Genetic Testing: To identify mutations in the XDH or *MOCOS* genes.
Kidney Imaging: Ultrasound or CT scan to detect kidney stones.
Timeline of Symptoms
Symptoms can manifest at any age, from infancy to adulthood. Some individuals remain asymptomatic throughout their lives. If symptoms develop, there is no fixed timeline:
Infancy/Childhood: Possible detection through routine urine tests or the presence of hematuria.
Adulthood: Symptoms may appear later in life, triggered by factors like dehydration or a diet high in purines.
Variable: The onset and progression of symptoms are highly variable and depend on individual factors such as genetics, diet, and fluid intake.
Important Considerations
Genetic Counseling: Important for families with a history of xanthinuria, as the condition is inherited.
Differential Diagnosis: It is crucial to differentiate xanthinuria from other causes of kidney stones, such as uric acid stones or calcium oxalate stones.
Long-Term Management: Requires ongoing monitoring and management to prevent complications.
Individualized Approach: Dietary and lifestyle recommendations should be tailored to the individual's needs and symptoms.
Rare Condition: Due to its rarity, xanthinuria may be overlooked or misdiagnosed.
Type II implication : If diagnosed, it is crucial to find out the type of Xanthine dehydrogenase deficiency since Type II also requires aldehyde oxidase deficiency which can cause neurological effects.