Combined Xanthine Oxidase and Aldehyde Oxidase Deficiency

Combined xanthine oxidase and aldehyde oxidase deficiency is a very rare inherited problem with body chemistry. In this condition, two enzymes called xanthine oxidase (or xanthine dehydrogenase) and aldehyde oxidase do not work properly or are completely missing. These enzymes usually help break down purines (building blocks of DNA) into uric acid and also help break down many drugs and natural chemicals in the body. When both enzymes are weak or absent, xanthine and hypoxanthine build up, and uric acid in blood and urine becomes very low. [1]

Combined xanthine oxidase and aldehyde oxidase deficiency is usually called hereditary xanthinuria type II. It is a very rare genetic disease where the body cannot properly break down purines (building blocks of DNA and RNA), because both the enzyme xanthine dehydrogenase/oxidase (XDH/XO) and the enzyme aldehyde oxidase (AOX) do not work well. This happens most often due to changes in a gene called MOCOS, which is needed to activate both enzymes. As a result, uric acid in blood and urine becomes very low, and xanthine builds up and can form stones in the kidneys and urinary tract, causing pain, blood in urine, and sometimes kidney damage. [1]

Doctors group this condition as a purine-metabolism disorder and as a form of “classical xanthinuria.” Type II is special because both XDH/XO and AOX are deficient, while type I usually affects XDH/XO alone. Studies using allopurinol “loading” tests and enzyme measurements showed that some patients cannot convert the drug allopurinol into its active form oxipurinol, which led scientists to discover the combined loss of both enzymes. [2]

Sometimes this combined deficiency happens by itself, mainly affecting xanthine and aldehyde oxidase (this is often called hereditary xanthinuria type II). In other cases, it happens as part of a more serious problem called molybdenum cofactor deficiency, where a common “helper” called molybdenum cofactor is missing, and three enzymes (xanthine oxidase, aldehyde oxidase, and sulfite oxidase) all fail. [2]

In many people with only combined xanthine oxidase and aldehyde oxidase deficiency, there may be no symptoms or only kidney-related problems such as stones. In contrast, when the problem is part of full molybdenum cofactor deficiency, babies often have severe brain damage, seizures, and early death if not treated. [3]

Other names

Doctors and scientists use several other names for this condition or for very closely related disorders. These names can appear in articles, lab reports, or genetic test results:

1. Hereditary xanthinuria type II – the classic term when the problem is mainly with xanthine dehydrogenase/oxidase and aldehyde oxidase. [4]

2. Combined xanthine oxidase and aldehyde oxidase deficiency – a descriptive name used in some medical databases. [5]

3. Hereditary xanthinuria, type 2 – another label that points to the same enzyme defect. [6]

4. Xanthine oxidase–sulfite oxidase deficiency or combined molybdoflavoprotein enzyme deficiency – used when xanthine oxidase, aldehyde oxidase, and sulfite oxidase are all affected because the molybdenum cofactor is missing. [7]

5. Molybdenum cofactor deficiency – the broader genetic disease that gives combined deficiency of xanthine dehydrogenase/oxidase and aldehyde oxidase, plus sulfite oxidase. [8]

Types

Because this is a very rare and complex condition, doctors often think of types based on which genes are affected and which enzymes are missing:

1. Type 1 – Hereditary xanthinuria type II (isolated dual enzyme defect)
   In this type, the main problem is in a gene called MOCOS, which is needed to “switch on” xanthine dehydrogenase/oxidase and aldehyde oxidase. Both enzymes are deficient, but sulfite oxidase is normal. Many people are symptom-free or mainly have kidney stones and low uric acid. [9]

2. Type 2 – Combined deficiency as part of molybdenum cofactor deficiency
   Here, mutations in genes like MOCS1, MOCS2, MOCS3, or GPHN/GEPH stop the body from making molybdenum cofactor. Without this cofactor, xanthine oxidase, aldehyde oxidase, and sulfite oxidase all fail. Babies usually present early with severe seizures and brain damage. [10]

3. Type 3 – Partial or variant combined deficiency
   In some reports, patients have very low but not zero enzyme activity, or unusual genetic changes. These people might have milder symptoms, later onset, or atypical test patterns. This group is sometimes called “variant xanthinuria” or “partial molybdenum cofactor deficiency.” [11]

4. Type 4 – Acquired or functional combined deficiency (very rare and secondary)
   Very severe liver disease, extreme malnutrition, or strong long-term use of medicines that block these enzymes might reduce xanthine oxidase and aldehyde oxidase activity and mimic genetic deficiency. This is not a true inherited form but can look similar in lab tests. [12]

Causes

In most patients, the main cause is an autosomal recessive gene mutation, which means both copies of a certain gene are changed. Below are 20 causes or strong contributing factors, explained in simple words.

1. Biallelic MOCOS gene mutations
   The most direct cause of hereditary xanthinuria type II is having harmful changes in both copies of the MOCOS gene, which makes an enzyme called molybdenum cofactor sulfurase. This enzyme is needed to activate xanthine dehydrogenase/oxidase and aldehyde oxidase. When MOCOS is faulty, both enzymes stay “switched off.” [13]

2. Compound heterozygous MOCOS variants
   Some patients inherit two different disease-causing changes in the MOCOS gene, one from each parent. Together these two different mutations still stop the enzyme from working and cause combined xanthine oxidase and aldehyde oxidase deficiency. [14]

3. Large deletions or rearrangements in MOCOS
   Rarely, a big piece of the MOCOS gene is missing or rearranged. This prevents normal protein production and again leads to dual enzyme deficiency. Some genetic tests only find point mutations, so special methods may be needed to detect these larger changes. [15]

4. MOCS1 gene mutations (molybdenum cofactor deficiency type A)
   Mutations in MOCS1 stop the first steps of molybdenum cofactor synthesis. Without this cofactor, xanthine dehydrogenase/oxidase and aldehyde oxidase cannot function, and sulfite oxidase is also lost. This gives combined deficiency plus severe neurological problems. [16]

5. MOCS2 gene mutations (molybdenum cofactor deficiency type B)
   Changes in MOCS2 affect another step of molybdenum cofactor production. Babies with biallelic MOCS2 mutations may have early seizures, feeding problems, and lab findings showing very low uric acid and high xanthine, meaning combined enzyme deficiency. [17]

6. MOCS3 gene mutations
   Newer research shows that MOCS3 is also part of the molybdenum cofactor pathway. Biallelic mutations in this gene can cause molybdenum cofactor deficiency with inactivity of xanthine dehydrogenase/oxidase and aldehyde oxidase. [18]

7. GPHN (gephyrin) / GEPH gene mutations
   The GPHN (also called GEPH) gene helps build the molybdenum cofactor. Pathogenic variants in both copies can lead to molybdenum cofactor deficiency, with combined loss of these molybdenum-dependent enzymes including xanthine oxidase and aldehyde oxidase. [19]

8. Autosomal recessive inheritance from two carrier parents
   The condition usually follows an autosomal recessive pattern. If both parents silently carry one faulty copy of MOCOS or a molybdenum cofactor gene, each pregnancy has a 25% chance of producing a child with combined deficiency. [20]

9. Consanguinity (parents being related)
   When parents are related by blood (for example, cousins), they are more likely to carry the same rare recessive mutation. This increases the chance that a child will inherit two faulty copies and develop the enzyme deficiency. [21]

10. Family history of hereditary xanthinuria or molybdenum cofactor deficiency
    Having siblings or close relatives diagnosed with hereditary xanthinuria type II or molybdenum cofactor deficiency strongly suggests a genetic cause and higher risk in the family. [22]

11. New (de novo) mutations
    Sometimes the harmful change in MOCOS or a molybdenum cofactor gene arises for the first time in the sperm or egg. This is called a de novo mutation. The parents may test negative, but the child still has a combined enzyme deficiency. [23]

12. Mutations in the XDH gene together with MOCOS pathway problems
    The XDH gene encodes xanthine dehydrogenase/oxidase. Some patients have XDH mutations plus separate defects in the molybdenum cofactor activation pathways, leading to deficient xanthine oxidase and aldehyde oxidase together. [24]

13. Severe molybdenum cofactor biosynthesis defects
    When molybdenum cofactor cannot be made at all, all molybdenum-dependent enzymes (including xanthine oxidase and aldehyde oxidase) become inactive. This “global” biosynthesis block is a direct cause of combined enzyme deficiency. [25]

14. Partial molybdenum cofactor deficiency
    Some patients have a partial defect, with small amounts of cofactor. The enzymes still work poorly, and their activity may drop further during illness, causing functional combined deficiency. [26]

15. Extreme nutritional molybdenum deficiency (theoretical contributor)
    True dietary molybdenum deficiency is extremely rare, but very low intake might reduce cofactor availability and further weaken already borderline enzyme activity in susceptible people. This would not usually be a sole cause, but a possible aggravating factor. [27]

16. Severe chronic liver disease
    Both xanthine oxidase and aldehyde oxidase are mainly produced in the liver. Advanced liver failure may lead to much lower enzyme levels and a secondary combined deficiency picture on blood tests, even without genetic mutations. [28]

17. Drugs that strongly inhibit xanthine oxidase and aldehyde oxidase
    Some medicines (such as allopurinol and other experimental drugs) strongly block these enzymes. In people with underlying genetic weakness, such drugs can create an almost complete functional deficiency, worsening xanthine build-up. [29]

18. Oxidative stress and reactive oxygen species imbalance
    Aldehyde oxidase is involved in producing and handling reactive oxygen species. Variants or stress that change this balance may worsen the impact of enzyme deficiency on tissues such as muscle and kidney. [30]

19. Co-existing sulfite oxidase deficiency in MoCD
    In molybdenum cofactor deficiency, sulfite oxidase also fails. Sulfite and S-sulfocysteine build up and cause severe brain damage. This combined toxicity makes the clinical picture far more serious than simple xanthinuria alone. [31]

20. Unknown or yet-undiscovered genetic factors
    Some patients with a clinical and biochemical picture of combined xanthine oxidase and aldehyde oxidase deficiency do not have mutations in known genes. This suggests there are still unknown genetic or regulatory causes that science has not fully discovered yet. [32]

Symptoms and signs

Symptoms can vary a lot, from no symptoms to severe brain disease, depending on whether only xanthine oxidase and aldehyde oxidase are affected or whether sulfite oxidase is also missing.

1. No symptoms (asymptomatic state)
   Many people with hereditary xanthinuria type II feel completely well and are only diagnosed when urine tests show high xanthine or very low uric acid, or when stones are found by chance. [33]

2. Kidney stones made of xanthine
   Xanthine is poorly soluble, so when its level in urine is high, xanthine stones may form. These stones can block the urinary tract, cause strong flank pain, and damage kidney tissue over time. [34]

3. Renal colic and flank pain
   When a xanthine stone moves in the ureter, it can cause sharp, cramping pain in the side or back, sometimes radiating to the groin. This is called renal colic and often brings patients to the emergency department. [35]

4. Blood in the urine (hematuria)
   Stones or crystals can scratch the lining of the urinary tract, leading to visible red or brown urine or microscopic blood picked up on a urine test. [36]

5. Frequent or painful urination
   Irritation from crystals and stones may cause burning when passing urine or the need to pass urine more often, especially when stones are near the bladder or urethra. [37]

6. Recurrent urinary tract infections
   Obstruction and residual urine from stones can make it easier for bacteria to grow, leading to repeated bladder or kidney infections, with fever and discomfort. [38]

7. Reduced kidney function or chronic kidney disease
   Long-standing blockage, high xanthine levels, and repeated infections can slowly damage kidney tissue, causing reduced kidney function, rising creatinine, and eventually chronic kidney disease in some patients. [39]

8. Muscle pain and cramps
   Xanthine may deposit in muscle and soft tissue, especially with intense exercise. Some patients report muscle pain, cramps, or tenderness, and very rarely myositis (inflammation of muscle). [40]

9. Muscle weakness and fatigue
   Chronic kidney problems, metabolic imbalance, or muscle involvement can cause a feeling of weakness, poor exercise tolerance, and easy tiredness. [41]

10. Joint pain or stiffness
    Abnormal purine metabolism may be linked with joint discomfort or stiffness, although classical gout (high uric acid) is usually not seen because uric acid is low. [42]

11. Poor growth and failure to thrive in infants with MoCD
    Babies with molybdenum cofactor deficiency often fail to gain weight, feed poorly, and do not grow as expected, because of severe neurological illness and feeding difficulties. [43]

12. Seizures (especially in neonatal period in MoCD)
    In combined deficiency that includes sulfite oxidase (MoCD), seizures often begin in the first days of life. They are usually frequent and difficult to control with standard medicines. [44]

13. Developmental delay and intellectual disability
    Because toxic sulfite and related compounds damage the brain in molybdenum cofactor deficiency, affected children often show severe delays in movement, speech, and learning skills. [45]

14. Abnormal muscle tone (hypotonia or spasticity)
    MoCD can cause floppy muscles (hypotonia) at first, followed by increased tone and stiff movements (spasticity) as brain injury progresses. [46]

15. Feeding problems and vomiting in infants
    Infants with severe forms may have trouble sucking or swallowing, vomit frequently, and need tube feeding. This is usually due to central nervous system involvement rather than the xanthine problem alone. [47]

Diagnostic tests

Doctors diagnose combined xanthine oxidase and aldehyde oxidase deficiency by putting together clinical signs, urine and blood tests, imaging, enzyme studies, and genetic tests. In mild hereditary xanthinuria type II, the main clues are very low uric acid, high xanthine, and sometimes kidney stones. In molybdenum cofactor deficiency, doctors also see high sulfite markers and severe brain symptoms. [48]

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Physical examination tests

1. Full physical examination and growth check
   The doctor checks height, weight, head size, vital signs, and overall appearance. In isolated hereditary xanthinuria type II, the exam may be almost normal. In molybdenum cofactor deficiency, the child may have poor growth, abnormal head shape, and signs of severe neurological disease. [49]

2. Abdominal and flank examination
   The doctor gently presses and taps over the abdomen and flanks to look for tenderness over the kidneys or bladder, suggesting stones or infection. A painful response over the kidney area can support the suspicion of xanthine stones. [50]

3. Neurological examination
   In babies or children with suspected molybdenum cofactor deficiency, the doctor checks alertness, muscle tone, reflexes, eye movements, and developmental level. Abnormal tone, poor head control, or seizures during exam point to serious brain involvement. [51]

4. Musculoskeletal and joint examination
   The clinician looks for muscle tenderness, weakness, and joint pain. This can help detect myositis or joint problems linked with xanthine deposits or long-standing kidney disease. [52]

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Manual tests

5. Manual muscle strength testing
   The doctor asks the patient to push or pull against resistance to check strength in different muscle groups. Reduced strength can support complaints of muscle pain or myositis in xanthinuria. [53]

6. Developmental milestone assessment (infants and children)
   For young children, doctors or therapists manually assess gross motor skills (rolling, sitting, walking), fine motor skills (grasping), speech, and social interaction. Major delays are common in severe molybdenum cofactor deficiency. [54]

7. Pain localization and palpation tests
   The doctor gently presses along the ureters, bladder area, and muscles to find the exact location of pain. This helps distinguish kidney colic from muscle or joint pain. [55]

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Laboratory and pathological tests

8. Serum uric acid and creatinine levels
   In hereditary xanthinuria type II and molybdenum cofactor deficiency, serum uric acid is usually very low or undetectable, while creatinine may rise if the kidneys are damaged. This pattern is a key biochemical clue. [56]

9. Urinary xanthine and hypoxanthine measurement
   Using specialized methods like high-performance liquid chromatography (HPLC), the lab measures xanthine and hypoxanthine in urine. Very high levels strongly suggest xanthinuria and combined xanthine oxidase deficiency. [57]

10. Urinary uric acid and creatinine ratio
    Very low urinary uric acid, especially when compared to creatinine, supports the diagnosis of hereditary xanthinuria or molybdenum cofactor–related enzyme deficiency. [58]

11. Urinary sulfite and S-sulfocysteine levels
    In molybdenum cofactor deficiency, urinary sulfite tests are positive, and levels of S-sulfocysteine are high. These markers show that sulfite oxidase is also deficient, confirming the broader cofactor problem. [59]

12. Allopurinol loading test
    Traditionally, doctors gave a small dose of allopurinol and then measured its breakdown product oxypurinol in urine. In type I xanthinuria, aldehyde oxidase still works, so oxypurinol appears. In type II, both xanthine oxidase and aldehyde oxidase are deficient, so oxypurinol is not formed. [60]

13. Genetic testing for MOCOS and XDH (hereditary xanthinuria)
    Sequencing of MOCOS and XDH genes can confirm hereditary xanthinuria types I and II. Finding biallelic pathogenic variants in MOCOS supports combined xanthine oxidase and aldehyde oxidase deficiency (type II). [61]

14. Genetic testing for MOCS1, MOCS2, MOCS3, and GPHN (MoCD)
    For suspected molybdenum cofactor deficiency, genetic panels or exome sequencing can detect biallelic pathogenic variants in MOCS1, MOCS2, MOCS3, or GPHN. These findings explain combined inactivity of xanthine dehydrogenase/oxidase and aldehyde oxidase plus sulfite oxidase. [62]

15. Enzyme activity assays in tissue or cultured cells
    In some centers, doctors measure xanthine dehydrogenase/oxidase, aldehyde oxidase, and sulfite oxidase activity in liver, intestinal biopsy, or cultured fibroblasts. Very low or absent activity of these enzymes confirms the biochemical diagnosis. [63]

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Electrodiagnostic tests

16. Electroencephalogram (EEG)
    In infants with seizures and suspected molybdenum cofactor deficiency, EEG records brain electrical activity. It often shows frequent abnormal discharges and a severely disturbed pattern, supporting the diagnosis of a major metabolic encephalopathy. [64]

17. Electromyography (EMG) and nerve conduction studies
    If there is marked muscle pain, weakness, or suspected myositis, EMG and nerve conduction tests can show whether the problem is mainly in muscle or nerves. This helps separate muscle injury from kidney-related weakness. [65]

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Imaging tests

18. Renal and bladder ultrasound
    Ultrasound uses sound waves to look at the kidneys and bladder without radiation. It can show xanthine stones, blockage, swelling of the kidneys (hydronephrosis), and chronic scarring. This is usually the first imaging test in suspected xanthinuria. [66]

19. CT scan or MRI of the urinary tract
    CT urography gives more detailed pictures of stones, their size and exact location, and any obstruction. MRI can help when radiation should be avoided. Xanthine stones may be less visible on plain X-rays, so CT is often more informative. [67]

20. Brain MRI or CT in suspected MoCD
    In molybdenum cofactor deficiency, brain imaging may show features like cerebral atrophy, cystic changes, or white matter injury. These changes, together with biochemical markers, strengthen the diagnosis of a severe combined molybdenum-dependent enzyme deficiency. [68]

Non-pharmacological treatments

1. High daily fluid intake
Drinking a lot of water is the single most important non-drug treatment. Extra fluid dilutes xanthine in the urine, lowers its concentration, and helps prevent crystals and stones from forming or getting larger. Doctors often suggest evenly spaced drinking across the whole day and extra fluid during hot weather, exercise, or illness to avoid dehydration, which can quickly raise stone risk. [1]

2. Low-purine diet
Purines in food are broken down into xanthine and uric acid. In this disease, uric acid is low but xanthine builds up; so limiting purine intake reduces the burden on the metabolic pathway. A low-purine diet means eating less organ meat, some fish (sardines, anchovies), yeast extracts, and large amounts of red meat, while focusing on grains, vegetables, fruits, and moderate animal protein as advised by a dietitian. [2]

3. Evenly spaced meals and fluids
Taking food and drinks at regular times helps keep purine load and urine concentration more stable over 24 hours. Long fasting followed by heavy meals can cause temporary spikes in purine breakdown, while long gaps without water increase urine concentration and crystal risk. A “little but often” pattern of food and fluid is often easier on the kidneys in this disease. [3] [4]

4. Avoiding dehydration triggers
Dehydration can come from fever, vomiting, diarrhea, strenuous exercise, or hot weather. For someone with xanthinuria type II, dehydration sharply increases the chance of stone formation or blockage. Doctors usually teach patients to increase fluids at the first sign of illness, and to seek medical help early if they cannot keep fluids down or if urine output becomes low or very dark. [5]

5. Targeted urine alkalinization with diet
Xanthine is more soluble in slightly alkaline urine. Diets rich in fruits and vegetables and lower in animal protein can gently raise urine pH. Foods naturally rich in citrate (like citrus fruits and some vegetables) may help, especially when combined with high fluid intake, although diet alone is usually not enough for strong alkalinization in severe cases. [6]

6. Regular kidney and bladder imaging
Even with good habits, stones can still form. Periodic ultrasound or other imaging lets doctors detect stones, urinary obstruction, or kidney swelling early, before serious damage occurs. Imaging schedules depend on age, symptoms, and prior stone history, and are usually customized by the nephrologist or urologist. [7]

7. Routine blood and urine tests
Regular labs help track kidney function, stone risk, and the overall metabolic pattern. Doctors may monitor creatinine (kidney function), electrolytes, uric acid (often very low), and sometimes xanthine levels or stone composition. Urinalysis can show crystals, blood, or infection. These results guide lifestyle advice and decisions about medicines or procedures. [8]

8. Prompt treatment of urinary infections (non-drug steps)
Warm fluids, frequent voiding, and good hygiene are simple but important non-drug measures to help prevent or support treatment of urinary infections. Although antibiotics are needed when infection is present, non-pharmacological steps reduce recurrence and prevent stagnation of infected urine behind stones or partial obstructions. [9]

9. Physical activity adjusted to kidney health
Gentle regular exercise supports general health, blood pressure, and weight. However, very intense activity with heavy sweating without adequate fluid replacement can increase dehydration risk. Patients are usually advised to choose moderate exercise, carry water, and adjust intensity if they are prone to stone episodes or have reduced kidney function. [10] [11]

10. Pain-coping and relaxation techniques
Renal colic (stone pain) can be extremely distressing. Controlled breathing, heat packs to the flank (if advised), distraction, and relaxation methods can reduce anxiety and improve how people cope while waiting for medical evaluation or while medicines start to work. These methods do not replace emergency care when pain is severe or associated with fever. [12]

11. Genetic counseling for patient and family
Because xanthinuria type II is an autosomal recessive disease, genetic counseling can explain recurrence risk for siblings and future children. Counselors also discuss carrier testing, prenatal options, and the importance of alerting doctors about the enzyme defect before prescribing certain purine-like medicines. [13]

12. Education about drug avoidance
Some purine-related drugs (for example, allopurinol or certain chemotherapy-like purine analogs) may behave unpredictably or be unsafe when XDH and AOX are deficient. Patients and families need clear written information to show to all healthcare providers, so that such drugs are avoided or used only with expert oversight. [14]

13. Written emergency plan
An emergency plan describes what to do if there is sudden severe flank pain, inability to pass urine, fever with chills, or vomiting. It may list the patient’s diagnosis, key lab features (very low uric acid, xanthinuria), and a reminder that this is a rare metabolic condition. This helps emergency doctors act quickly and safely. [15]

14. School or workplace support
Children and adults may need flexible bathroom access, permission to carry water, and time off for hospital visits. Clear notes from the specialist can help schools and employers understand that frequent drinking and restroom breaks are medical needs, not habits. [16]

15. Monitoring blood pressure and heart-kidney health
Chronic kidney stress from stones or obstruction can slowly affect blood pressure and heart health. Regular blood-pressure checks, heart-healthy lifestyle, and early treatment of hypertension lower long-term risk of complications. This is part of general chronic-kidney-disease care. [17]

16. Avoiding crash weight-loss and extreme diets
Very low-calorie or extreme high-protein diets can change purine metabolism and kidney stone risk. For example, strict ketogenic diets have been associated with kidney stone formation and changes in urinary citrate. Any special diet should be supervised by professionals who understand the kidney risk. [18]

17. Good oral health and infection control
Because kidney function is precious in this disease, patients should reduce avoidable infection and inflammation in the body, including dental infections. Good dental care, vaccinations as recommended, and early treatment of infections help protect overall health and may reduce systemic stress on kidneys. [19]

18. Psychosocial and mental-health support
Living with a very rare disorder can feel isolating. Counseling, patient-support communities, and family education can reduce anxiety and depression, improve treatment adherence, and help people cope with uncertainty about the future. [20]

19. Participation in registries or research (when available)
Joining rare-disease registries or carefully designed research studies can give access to expert teams and help generate better knowledge about natural history, long-term outcomes, and possible new treatments like gene or enzyme replacement therapies. Participation is always voluntary and must be discussed carefully with the care team. [21]

20. Family screening and early childhood monitoring
Because siblings can share the same genetic defect, early screening of at-risk children (by uric acid levels, urine analysis, and genetics) can allow earlier lifestyle measures before stones and kidney damage develop. Families can also be taught early warning signs like blood in urine or recurrent urinary infections. [22]

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Drug treatments

Very important: There is no specific drug approved by the FDA that cures combined xanthine oxidase and aldehyde oxidase deficiency. Most medicines are used to treat complications like stones, pain, infection, and kidney failure. Some purine-related drugs must be avoided. All doses below are typical adult examples from prescribing information; only your own doctor can choose the right drug and dose for you. [1]

1. Potassium citrate (Urocit-K)
Potassium citrate is an oral alkali that raises urine pH and increases urinary citrate, which can help prevent certain kidney stones and may also make xanthine more soluble. Labels describe total doses such as 30–100 mEq per day divided with meals, but exact dosing must be individualized. Common side effects include stomach upset and high potassium in at-risk patients. [2]

2. Sodium bicarbonate tablets
Sodium bicarbonate is another alkali that can raise urine pH when potassium citrate is not suitable. It is often used in chronic kidney disease to correct metabolic acidosis and can also reduce the tendency for crystals to form in acidic urine. Side effects can include fluid overload and increased blood pressure, so monitoring is needed. [3] [4]

3. Intravenous isotonic fluids (e.g., 0.9% saline)
During severe stone attacks, dehydration, or vomiting, IV fluids are used in hospital to quickly restore circulation volume and promote urine flow. Typical rates depend on age, blood pressure, and kidney function. Over-rapid infusion can stress the heart or lungs, so doctors adjust carefully. [5]

4. Paracetamol (acetaminophen)
Acetaminophen is a common pain and fever medicine that is often preferred over NSAIDs when kidney function is fragile. Standard labels describe maximum adult doses up to 3–4 g per day in divided doses, but lower limits are used in chronic diseases. Overdose can cause serious liver injury, so strict dosing and medical supervision are essential. [6] [7]

5. NSAIDs (e.g., ibuprofen, ketorolac – carefully used)
Non-steroidal anti-inflammatory drugs can relieve acute renal colic by reducing prostaglandin-mediated pain and inflammation in the ureter. Labels warn that NSAIDs can reduce kidney blood flow and worsen kidney function, especially in dehydrated or chronic-kidney-disease patients, so they must be used for short periods and under close supervision. [8]

6. Opioid analgesics (e.g., morphine)
For very severe stone pain, opioid medicines may be used in hospital. They act on central nervous system receptors to reduce pain perception. Side effects may include drowsiness, nausea, constipation, and respiratory depression. Because of dependence and overdose risks, opioids are strictly controlled and used only when absolutely needed. [9] [10]

7. Tamsulosin (Flomax) – medical expulsive therapy
Tamsulosin is an alpha-1A–adrenergic blocker approved for benign prostate enlargement, but it is often used off-label to help small ureteric stones pass by relaxing the smooth muscle of the ureter. The usual adult dose is 0.4 mg once daily after the same meal each day. Side effects can include dizziness, low blood pressure, and ejaculation changes. [11]

8. Antibiotics for urinary tract infection (e.g., cephalosporins)
Stones can block urine flow and predispose to infection. When infection is present, antibiotics based on urine culture are essential. Cephalosporins or other agents are chosen according to local resistance patterns and kidney function. Side effects depend on the drug and may include allergy, diarrhea, and changes in gut flora. [12]

9. Antiemetics (e.g., ondansetron)
Severe stone pain can be associated with nausea and vomiting, which worsens dehydration. Ondansetron and similar medicines block serotonin receptors in the gut and brain to reduce nausea. Labels describe various oral and IV dosing schedules; common side effects include headache and constipation, and high doses can affect heart rhythm. [13] [14]

10. Antispasmodics (e.g., hyoscine butylbromide, where available)
These drugs relax smooth muscle in the gut and urinary tract and may help some patients with crampy pain related to stones. They work by blocking muscarinic acetylcholine receptors. Side effects can include dry mouth, blurred vision, and urinary retention, so they must be used carefully in patients with urinary obstruction. [15] [16]

11. Blood-pressure medicines (ACE inhibitors/ARBs)
If chronic kidney stress leads to high blood pressure, ACE inhibitors or angiotensin-receptor blockers may be used, as they are kidney-protective in many chronic kidney diseases. They reduce intraglomerular pressure and protein leakage. Side effects include cough (ACE inhibitors), high potassium, and changes in kidney function, so labs must be checked. [17]

12. Erythropoiesis-stimulating agents
In advanced kidney damage, anemia may appear due to low erythropoietin. Erythropoiesis-stimulating agents mimic this hormone and stimulate red-blood-cell production. Labels stress careful dosing to avoid very high hemoglobin levels, which can raise stroke and clot risk. Iron levels must also be monitored and supplemented if low. [18] [19]

13. Phosphate binders and vitamin D analogs
If chronic kidney disease causes high phosphate and disordered mineral metabolism, phosphate-binding agents and active vitamin D forms may be used. They help protect bones and blood vessels from calcification. Side effects can include high calcium, low phosphate, and gastrointestinal symptoms, so they are adjusted according to labs. [20]

14. Allopurinol – usually avoided here
Allopurinol is a xanthine oxidase inhibitor widely used for gout and high uric acid. In classical xanthinuria, especially type II, XDH/XO and AOX are deficient, and allopurinol may not be properly converted to oxipurinol. Publications and recent genetic studies warn that purine drugs such as allopurinol can cause unpredictable toxicity in MOCOS-related xanthinuria, so they are generally not recommended. [21]

15. Febuxostat (Uloric) – also generally not recommended here
Febuxostat is another xanthine oxidase inhibitor for gout. Its label warns about cardiovascular risk and states it is not recommended for asymptomatic hyperuricemia. In a patient whose XO is already deficient genetically, using febuxostat offers no clear benefit and may add risk, so specialists usually avoid it in hereditary xanthinuria. [22]

16. Lesinurad (Zurampic) – urate-lowering drug to avoid
Lesinurad increases uric-acid excretion and is indicated only together with a xanthine oxidase inhibitor for gout. In xanthinuria type II, uric acid is already very low, and the core problem is xanthine buildup and kidney risk. Using lesinurad here would be inappropriate and potentially harmful, so it is a drug to avoid. [23]

17. Purine-analog chemotherapy drugs – used with great caution or avoided
Some chemotherapy and immunosuppressive agents are purine analogs and depend on purine metabolism and detoxification pathways that involve AOX or related enzymes. In MOCOS-deficient xanthinuria type II, experts recommend extreme caution or alternative drugs where possible, to avoid unexpected accumulation and toxicity. [24]

18. Tailored chronic-kidney-disease medication bundles
If kidney damage progresses, patients may receive a bundle of medicines similar to other CKD patients (for blood pressure, phosphate, anemia, bone health). The exact combination is individualized, and there is no single “xanthinuria pill.” The main message is that general CKD standards are applied, adjusted for this rare metabolic background. [25]

19. Vaccines (not a “stone drug” but part of drug care)
Up-to-date vaccinations (e.g., against flu, pneumonia, hepatitis B as indicated) reduce the risk of infections that can worsen kidney function or require nephrotoxic drugs. Vaccines stimulate the immune system in a controlled way and are an important part of chronic-disease management plans. [26]

20. Individualized clinical-trial medicines
Some patients may be offered enrollment in clinical trials for novel therapies, such as metabolic modulators, gene-based treatments, or new stone-prevention strategies. These medicines are experimental, given under strict protocols, and are not standard of care. Decisions are made case by case with specialist teams. [27]

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Dietary molecular supplements

Supplements are not a substitute for medical care or a low-purine, high-fluid diet. Many have limited data in this precise disease; most evidence comes from kidney-stone or kidney-health research in general. Always ask your doctor before using any supplement.

1. Potassium citrate as a supplement form
When prescribed, potassium citrate is technically a drug, but it functions as a “molecular supplement” of citrate and potassium. It increases urinary citrate and pH, which can lower crystallization of some stone-forming substances. In xanthinuria, it may help reduce xanthine precipitation as part of a wider plan. [1]

2. Magnesium supplements
Magnesium can bind certain stone-forming anions and may reduce the risk of calcium-based stones in some settings. In patients with normal magnesium and kidney function, moderate oral magnesium may be considered, but in chronic kidney disease magnesium can accumulate, so supplementation must be doctor-guided. [2] [3]

3. Vitamin B6 (pyridoxine)
Vitamin B6 is involved in amino-acid metabolism and is sometimes used in other metabolic stone diseases (like primary hyperoxaluria). While data in xanthinuria type II are limited, some clinicians consider low-dose B6 as a supportive metabolic co-factor. Excessive doses can cause nerve damage, so medical supervision and modest dosing are essential. [4]

4. Omega-3 fatty acids
Omega-3 supplements support heart and vascular health and may slightly lower inflammation markers. For people with chronic kidney risk, maintaining cardiovascular health is very important. They are usually taken in doses of 1–3 g combined EPA/DHA per day, but they can increase bleeding tendency at high doses or with certain medicines. [5] [6]

5. Vitamin D (with monitoring)
Vitamin D is important for bone and immune health. In chronic kidney disease, vitamin D processing is altered, and specific active forms may be needed. Supplementation must be guided by measured levels and kidney status, because too much vitamin D can raise calcium and phosphate and worsen calcification. [7]

6. Probiotics (gut microbiome support)
A healthy gut microbiota may influence some aspects of metabolism and inflammation. Probiotic foods or supplements (like certain yogurts or capsules) are being studied in kidney disease and stone prevention, although data are still evolving. They are generally safe for many people but may be risky in severely immunocompromised patients. [8]

7. Antioxidant vitamins (C and E – with caution)
Antioxidants such as vitamins C and E may help fight oxidative stress, but high-dose vitamin C can increase oxalate formation and raise risk for oxalate stones in some people. In xanthinuria, where the main issue is xanthine stones, doctors still usually prefer moderate doses and avoid mega-dosing. [9] [10]

8. Coenzyme Q10
CoQ10 participates in mitochondrial energy production and has been studied in some kidney and cardiovascular conditions. Evidence is not specific for xanthinuria, but in selected patients it may be considered as part of general oxidative-stress-reduction strategies. Dosing and interactions (for example with warfarin) must be checked. [11]

9. Citrate-rich natural drinks (e.g., lemon water)
Homemade lemon or citrus drinks provide natural citrate, which can modestly increase urinary citrate and pH. This is not as strong or controlled as prescribed potassium citrate but may be a useful supportive habit in people without contraindications such as severe reflux or citrus allergy. Sugar should be kept low to protect teeth and metabolism. [12]

10. General multivitamin (kidney-safe formula)
In some patients with dietary limits, a kidney-safe multivitamin (without excess vitamin A, vitamin C, or minerals that accumulate in kidney disease) may be used to prevent deficiencies. These products are formulated with adjusted doses; the exact choice depends on lab values and kidney stage. [13]

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Immunity-boosting, regenerative and stem-cell–related drugs

At present, there is no proven “immune booster” or stem-cell drug specifically approved for combined xanthine oxidase and aldehyde oxidase deficiency. Most ideas here are theoretical or based on general CKD care and rare-disease research.

1. Vaccines as controlled immune support
Routine vaccines (influenza, pneumococcal, hepatitis B where indicated) are the safest and best-studied way to help the immune system handle infections. Keeping up-to-date immunizations reduces hospitalizations and exposure to nephrotoxic emergency antibiotics, indirectly protecting kidney health. [1]

2. Nutritional immune support
Adequate protein (within renal limits), vitamins, and minerals is essential for immune cells to function and repair tissue. Inadequate intake leads to poor wound healing and higher infection risk. Dietitians help balance protein restriction (for advanced CKD) with the need to avoid malnutrition and muscle loss. [2]

3. Hematopoietic stem-cell transplantation (HSCT) – experimental
In some severe metabolic or immunologic disorders, HSCT can provide new enzyme-producing cells. For classical xanthinuria type II due to MOCOS mutations, HSCT is not standard, and only theoretical or isolated case discussions exist. Risks include graft-versus-host disease, infections, and treatment-related mortality, so it is reserved for conditions with proven benefit. [3]

4. Future gene-therapy approaches
Because the disease is monogenic (often MOCOS-related), gene therapy is a logical future approach. Research in other monogenic kidney and metabolic diseases is advancing, and similar viral or RNA-based delivery might one day correct the enzyme defect in liver or kidney cells. For now, this remains a research concept, not a clinical treatment. [4]

5. Organ transplantation in end-stage kidney failure
If repeated stones and obstruction eventually lead to end-stage kidney disease, kidney transplantation may be considered. The metabolic defect (low uric acid, xanthinuria) persists, so careful management is still needed, but a new kidney can restore filtration and waste removal. Immunosuppressive drugs are then required lifelong to prevent rejection. [5]

6. Experimental small-molecule modifiers
In animal models, researchers sometimes test small molecules that modulate purine metabolism or protect kidney tissue from obstruction-related inflammation and fibrosis. These drugs are not specific for human xanthinuria type II yet, but may in the future reduce stone-induced damage or oxidative stress in kidneys. [6]

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Surgical treatments

1. Ureteroscopy with laser stone fragmentation
When a stone is stuck in the ureter and does not pass, doctors can insert a thin scope through the urethra and bladder into the ureter, visualize the stone, and break it with a laser. The small fragments are removed or left to pass. This relieves obstruction, preserves kidney function, and resolves pain. [1]

2. Percutaneous nephrolithotomy (PCNL)
For large kidney stones, a small channel is created through the skin into the kidney under imaging guidance. A scope is used to break and remove stones. PCNL is chosen when stones are too big or too hard for ureteroscopy or shock-wave therapy and is important to prevent repeated obstruction and kidney damage. [2]

3. Shock-wave lithotripsy (where suitable)
External shock waves are focused on a stone to break it into smaller pieces that can pass more easily. Its usefulness depends on stone size, location, and composition; some xanthine stones may be less responsive. It is non-invasive and often used for selected stones to avoid more invasive surgery. [3]

4. Temporary ureteral stent placement
If swelling or a stone blocks urine flow, a thin plastic tube (stent) can be placed inside the ureter to allow urine to bypass the blockage. This is often done together with other procedures and is removed later. It quickly protects kidney function and reduces infection risk from stagnant urine. [4]

5. Nephrectomy (removal of a non-functioning kidney)
In rare, severe cases where one kidney is badly damaged, infected, or non-functioning and is causing ongoing complications, surgeons may remove that kidney. The decision is taken very carefully, considering overall kidney function, the condition of the other kidney, and the long-term needs of the patient. [5]

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Prevention tips

1. Drink enough water every day so that urine stays pale yellow and you rarely feel very thirsty. [1]

2. Follow a low-purine eating pattern guided by a dietitian to reduce purine load on the pathway. [2]

3. Avoid long periods of dehydration during illness, sports, or heat; increase fluids early when sick. [3]

4. Keep regular follow-up with your metabolic or kidney specialist, even when you feel well. [4]

5. Learn and teach family about drugs that should be avoided (like allopurinol and certain purine analogs) and always show your rare-disease card to new doctors. [5]

6. Treat urinary infections quickly and completely to prevent damage behind obstructed urine. [6]

7. Work with your doctor to manage blood pressure, cholesterol, and blood sugar to protect kidneys long term. [7]

8. Avoid crash diets, extreme high-protein plans, or unsupervised supplements that may stress kidneys or promote stones. [8]

9. Keep up-to-date with vaccinations to reduce infection burden and kidney-damaging illness. [9]

10. Consider family and genetic counseling so relatives at risk can be tested and start preventive care early. [10]

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When to see a doctor

You should see a doctor regularly for planned follow-ups, blood tests, and imaging, even when you feel well, because stones and kidney damage can develop silently. You should seek urgent medical care if you have strong side or back pain, pain that comes in waves, burning or difficulty when passing urine, blood in urine, fever with chills, vomiting that stops you from drinking, swelling of the legs or face, very little urine, or severe tiredness and shortness of breath. These signs may mean stone colic, obstruction, infection, or acute kidney injury and need fast treatment to protect your kidneys and overall health. [1]

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What to eat and what to avoid

1. Eat: plenty of water-rich foods (fruits and vegetables) plus water between meals to keep urine dilute. [1]

2. Eat: moderate portions of lean protein (chicken, fish, eggs) as guided by your kidney team; avoid very high-protein “body-builder” diets. [2]

3. Eat: whole grains, beans (in moderation if purine content is an issue), and healthy fats like olive oil and small amounts of nuts if your kidney doctor agrees. [3]

4. Eat: citrus fruits or low-sugar citrus drinks (like lemon water) to increase natural citrate, unless you have specific contraindications. [4]

5. Avoid or limit: organ meats (liver, kidney, sweetbreads), game meats, and some oily fish (anchovies, sardines) which are high in purines. [5]

6. Avoid: sugary soft drinks and high-fructose beverages that can worsen metabolic health and stone risk. Choose water as your main drink. [6]

7. Avoid: crash diets, fasting, or very restrictive eating plans without specialist advice. [7]

8. Avoid: unnecessary over-the-counter painkillers (especially NSAIDs) without asking your kidney doctor first. [8]

9. Avoid: high-dose vitamin C supplements and unproven “kidney cleanse” products which can be harmful. [9]

10. Balance: overall calories so that you maintain a healthy weight, because obesity, diabetes, and high blood pressure all make kidney outcomes worse. [10]

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Frequently asked questions

1. Is combined xanthine oxidase and aldehyde oxidase deficiency the same as gout?
No. Gout is usually caused by high uric acid. In this disease, uric acid is very low, and the problem is buildup of xanthine and possible kidney stones. Typical gout medicines that lower uric acid (allopurinol, febuxostat, lesinurad) are not helpful and may be risky here. [1]

2. How common is this condition?
Hereditary xanthinuria type II is extremely rare, with only a small number of families reported worldwide. Because it is autosomal recessive and may cause few symptoms in some people, it may be under-diagnosed. Many doctors will never see a patient with this disease, which is why written information is so important. [2]

3. What causes the enzyme deficiency?
Most known cases are due to changes (variants) in the MOCOS gene, which encodes a protein that sulfurates the molybdenum cofactor needed for both xanthine dehydrogenase/oxidase and aldehyde oxidase to function. When MOCOS is defective, both enzymes lose activity, leading to xanthinuria type II. [3]

4. What symptoms do people usually have?
Some people are discovered incidentally because of very low serum uric acid. Others develop kidney or urinary stones with flank pain, hematuria (blood in urine), urinary infections, or, in severe cases, kidney failure from repeated obstruction. A few may remain almost symptom-free for many years. [4]

5. How is the diagnosis made?
Doctors usually suspect the diagnosis when blood uric acid is markedly low and xanthine is detected in urine or stones. Further testing can include enzyme studies and genetic testing, especially of MOCOS or XDH genes. Specialized centers may use allopurinol loading tests and detailed metabolic panels to separate type I and type II. [5]

6. Is there any cure right now?
There is currently no cure that fully corrects the enzyme defect. Treatment focuses on preventing stones, protecting kidneys, and avoiding harmful medicines. Future therapies such as gene therapy or enzyme replacement may become possible as research advances, but they are not yet available in routine practice. [6]

7. Can children with this condition live a normal life?
With early diagnosis, careful fluid and diet management, and prompt treatment of stones and infections, many children can grow and develop well. The main goal is to protect kidney function over decades. Life with a rare disease can be challenging, but good support and specialist care make a big difference. [7]

8. Are family members at risk?
Yes. Because the condition is autosomal recessive, each sibling of an affected person has a 25% chance of also being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier (if both parents are carriers). Genetic counseling and testing can clarify risk. [8]

9. Why is allopurinol dangerous in some patients with this disorder?
Allopurinol is normally converted to oxipurinol by xanthine oxidase and aldehyde oxidase. In type II xanthinuria, both enzymes are deficient, so the drug may not be processed normally and could accumulate or behave unpredictably. Modern reports advise avoiding purine drugs in people with confirmed MOCOS-related xanthinuria. [9]

10. Does low uric acid cause any problems itself?
Very low uric acid is unusual, but the main problems in this disease come from xanthine buildup and stone formation, not from low uric acid alone. In many people, low uric acid causes no direct symptoms, but it is an important clue that points doctors toward purine-metabolism disorders. [10]

11. Is this the same as molybdenum cofactor deficiency?
No, but they are related. Molybdenum cofactor deficiency leads to severe combined loss of sulfite oxidase, xanthine oxidase, and aldehyde oxidase and usually causes severe neurological disease in infancy. Xanthinuria type II is milder and mainly affects purine metabolism and kidney stones. Both involve molybdenum-dependent enzymes. [11]

12. Can diet alone control the disease?
Diet and fluid habits are extremely important but may not be enough in every case. Some patients still develop stones and need medicines, procedures, or surgery. Lifestyle measures are the foundation, and medical/surgical treatments are added when needed. [12]

13. How often should I have follow-up tests?
The frequency depends on age, kidney function, and stone history. Many specialists recommend at least yearly review when stable, with more frequent visits and imaging if stones are active, new symptoms appear, or kidney function declines. Children often need closer monitoring during growth. [13]

14. Can pregnancy be safe with this condition?
Pregnancy is possible, but requires close planning and monitoring by obstetric and nephrology teams. Fluid needs change, and the risk of stones, infections, and kidney stress can increase. Some medicines used in kidney disease or stone prevention may not be safe in pregnancy, so pre-pregnancy counseling is essential. [14]

15. Where can families find more help?
Families can look for rare-disease organizations, kidney foundations, and online communities focused on hereditary xanthinuria or purine-metabolism disorders. These groups share educational materials, expert-center lists, and emotional support. Always confirm medical advice from the internet with your own specialist before making changes. [15],

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: February 18, 2025.