Hereditary xanthinuria type 2 is a very rare, life-long (genetic) disease of purine metabolism, which is the way the body breaks down some building blocks of DNA and RNA. In this type, the body cannot properly use two enzymes called xanthine dehydrogenase and aldehyde oxidase, so a substance called xanthine builds up and another substance called uric acid becomes very low in blood and urine. This extra xanthine can make crystals and stones in the kidneys and urinary tract and can sometimes collect in muscles and joints, while many people have no symptoms at all.
Hereditary xanthinuria type 2 is a very rare inherited disorder of purine metabolism in which the body cannot properly break down the substances hypoxanthine and xanthine into uric acid. Because of this enzyme problem, large amounts of xanthine build up in blood and urine, and uric acid levels become very low. Over time, the extra xanthine can form crystals and stones in the kidneys and urinary tract, which may damage the kidneys if not recognized. Hereditary xanthinuria type 2 belongs to the group called “classical xanthinuria.”
Causes and genetics of hereditary xanthinuria type 2
Hereditary xanthinuria type 2 is caused by harmful changes (mutations) in the [MOCOS gene]. This gene gives instructions for making an enzyme called molybdenum cofactor sulfurase. That enzyme is needed to “switch on” two other enzymes: xanthine dehydrogenase and aldehyde oxidase. When MOCOS does not work, both enzymes are inactive. As a result, the body cannot convert hypoxanthine to xanthine and xanthine to uric acid in the normal way, so xanthine accumulates. The condition is inherited in an autosomal recessive pattern, which means a child must receive a faulty copy of the gene from both parents to develop the disease.
Hereditary xanthinuria type 2 is inherited in an autosomal recessive way. This means a person gets one non-working copy of a gene from each parent, so both gene copies are changed. The main gene for type 2 is called MOCOS (molybdenum cofactor sulfurase). Changes (mutations) in this gene stop the enzyme from “turning on” xanthine dehydrogenase and aldehyde oxidase, so both enzymes are missing or very weak.
Because these enzymes do not work, hypoxanthine and xanthine cannot be fully broken down into uric acid. Blood and urine tests in these patients usually show very low or almost zero uric acid and high xanthine and hypoxanthine. This pattern is a key clue for doctors to think about hereditary xanthinuria type 2.
Other names
Doctors and scientists use several other names for this condition. Many of these names are also used for hereditary xanthinuria in general, but they still apply to type 2:
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Hereditary xanthinuria type II (Type 2 xanthinuria)
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Xanthinuria, type II (XAN2)
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Classical xanthinuria type 2
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Hereditary xanthinuria (when the type is not specified)
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Classic xanthinuria
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Xanthine stone disease
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Xanthic urolithiasis (xanthine stone formation in the urinary tract)
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Xanthine oxidase deficiency (used broadly; type 2 also has aldehyde oxidase deficiency)
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Xanthine dehydrogenase/oxidase deficiency (classical xanthinuria)
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Purine metabolism disorder with dual deficiency of xanthine dehydrogenase and aldehyde oxidase
These different names all point to the same basic problem: inherited lack of the enzymes needed to finish breaking down purines into uric acid.
Types
There are several related conditions in the “xanthinuria” group. Knowing the types helps doctors understand which enzyme is missing and how to test for it.
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Hereditary xanthinuria type I – In this type, only xanthine dehydrogenase is missing or does not work. It is usually caused by changes in the XDH gene. Patients have very low uric acid and high xanthine, but aldehyde oxidase is still working.
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Hereditary xanthinuria type II (the topic here) – In this type, both xanthine dehydrogenase and aldehyde oxidase do not work because of mutations in the MOCOS gene. This causes the same low uric acid and high xanthine as type I, but also loss of aldehyde oxidase activity, and patients cannot properly handle some medicines such as allopurinol.
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Conditions that can look similar (sometimes called “type III”) – Some people have a broader molybdenum cofactor deficiency, which also affects another enzyme called sulphite oxidase. This is now usually treated as a separate disease group, but it can also give low uric acid and high xanthine.
Even inside type 2, there can be different mutations in the MOCOS gene, such as missense, nonsense, or splice-site changes, and these may cause partial or complete loss of enzyme activity, but all of them lead to the same pattern of high xanthine and low uric acid.
Causes
General idea
The main cause of hereditary xanthinuria type 2 is a harmful change in both copies of the MOCOS gene. This gene problem is present from birth and is passed down in families in an autosomal recessive way. Other “causes” are really factors that increase the chance that a child will inherit these gene changes.
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Mutation in the MOCOS gene – The direct cause is a disease-causing mutation in the MOCOS gene, which gives instructions for the molybdenum cofactor sulfurase enzyme. When this enzyme is faulty, it cannot activate xanthine dehydrogenase and aldehyde oxidase, so both enzymes stay “off”.
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Autosomal recessive inheritance – Type 2 xanthinuria happens when a person inherits one mutated MOCOS gene from each parent, so both copies are affected. Having only one changed gene (being a “carrier”) usually does not cause disease.
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Both parents are carriers – If both parents carry one non-working MOCOS gene, each child has a 25% chance to have the disease, 50% chance to be a carrier, and 25% chance to have two normal copies. This carrier pattern is the main family-level cause.
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Family history of hereditary xanthinuria – Having a brother, sister, or other close relative with hereditary xanthinuria strongly increases the chance that other children in the family may also have the same gene changes.
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Consanguinity (parents related by blood) – When the parents are related (such as cousins), they are more likely to carry the same rare gene mutation, so the chance that a child gets two copies of the same MOCOS mutation is higher.
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Founder mutations in some communities – In some small or isolated populations, a single ancient MOCOS mutation may be more common (“founder effect”), so the disease is seen more often in certain families from that group, even though it is very rare overall.
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Homozygous mutations (same change on both alleles) – If a person inherits the same mutation from both parents (homozygous), the enzyme may lose almost all function, making symptoms more likely.
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Compound heterozygous mutations (two different changes) – Sometimes each parent passes a different damaging mutation in MOCOS. Together these two different changes still stop the enzyme from working properly and cause disease.
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Missense mutations in MOCOS – A missense mutation changes one amino acid in the enzyme protein. This can cause the enzyme to fold incorrectly or become unstable so that it cannot activate xanthine dehydrogenase and aldehyde oxidase.
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Nonsense or frameshift mutations – These gene changes introduce a “stop” signal or shift the reading frame, producing a short, non-functional protein. This kind of mutation often leads to complete loss of molybdenum cofactor sulfurase activity.
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Splice-site mutations – Some mutations affect the places where the gene message is cut and joined (splicing). Wrong splicing can remove or insert pieces, again creating a non-working enzyme.
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Defect in molybdenum cofactor sulfur insertion – The MOCOS enzyme normally adds sulfur to a special small molecule (molybdenum cofactor) so it can activate xanthine dehydrogenase and aldehyde oxidase. When this step fails, both enzymes remain inactive.
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Loss of xanthine dehydrogenase activity – Because of the MOCOS defect, xanthine dehydrogenase cannot convert hypoxanthine and xanthine into uric acid. This loss of activity is a direct biochemical cause of high xanthine levels.
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Loss of aldehyde oxidase activity – The same MOCOS problem also disables aldehyde oxidase. This is what makes type 2 different from type 1 and explains why people with type 2 cannot metabolize some drugs like allopurinol normally.
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Disturbed purine degradation pathway – Because the end steps of purine breakdown are blocked, xanthine and hypoxanthine accumulate. This disturbed pathway is a biochemical cause of the crystal and stone formation seen in the kidneys.
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Chronic high xanthine excretion in urine – Over time, the continuous loss of high xanthine levels in urine leads to crystal and stone formation, which is the main organ-level cause of kidney symptoms.
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Tissue deposition of xanthine – Xanthine can also deposit in muscles and joints, leading in some patients to muscle pain (myositis) or joint problems (arthropathy). These deposits are a local cause of pain and inflammation.
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Unrecognized carriers in the family – Because most carriers are healthy, families may not know the mutation exists. This silent carrier state in a population is a social and genetic cause for new affected children.
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Lack of newborn screening – In most countries there is no standard newborn screening for hereditary xanthinuria. Without testing, affected children may grow up with the mutation unnoticed until stones or other problems appear.
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High purine intake triggering symptoms in susceptible people – The genetic defect is the main cause, but eating a very high-purine diet (for example, large amounts of certain meats and organ meats) may increase xanthine load and can help bring out symptoms such as stones in people who already have type 2 xanthinuria.
Symptoms
Not everyone with hereditary xanthinuria type 2 has symptoms. Many people are found by accident when blood or urine tests show low uric acid. When symptoms do happen, they are usually related to xanthine crystals and stones in the kidneys or to xanthine deposits in other tissues.
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No symptoms (asymptomatic) – A large number of people with hereditary xanthinuria, including type 2, feel completely well. The disease is found only because routine tests show very low uric acid or because a sibling is tested.
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Flank or side pain – Pain in the side or back (in the area of the kidneys) is common when xanthine stones block the flow of urine. The pain can be sharp and may come in waves, similar to other kidney stones.
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Blood in the urine (hematuria) – Xanthine crystals and stones can scratch the lining of the urinary tract, causing visible red urine or blood seen only under the microscope.
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Frequent urination – Irritation from stones and crystals can make a person feel they need to pass urine often, sometimes only small amounts each time.
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Painful urination (dysuria) – Passing urine can burn or hurt when stones or crystals are present in the bladder or urethra, or when an infection develops on top of the stone disease.
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Passing small stones or sandy material – Some patients notice tiny stones or a sandy, gritty material in the urine. This often represents xanthine stones breaking apart and moving out of the urinary tract.
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Recurrent urinary tract infections – Stones can block urine flow and provide a place where bacteria can grow. This can cause repeated bladder or kidney infections, with burning, fever, or strong-smelling urine.
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Acute renal colic attacks – When a stone suddenly blocks a ureter, there can be a very sudden, severe pain attack (renal colic) with restlessness, nausea, and vomiting, similar to other kidney stone diseases.
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Reduced urine output or blockage – Large stones can block the flow of urine completely or nearly completely, leading to very low urine volume, bladder fullness, or even emergency urinary retention.
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Signs of kidney failure – If many stones damage the kidneys over time, people may develop swelling of the legs and face, tiredness, poor appetite, and changes in blood pressure due to chronic kidney disease.
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General fatigue and weakness – Chronic pain, infections, or decreased kidney function can make patients feel tired, weak, or low in energy, even without specific pain at a given time.
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Poor growth in children – In some children, repeated stone problems, infections, and chronic kidney issues may lead to poor weight gain and slow growth compared with healthy peers.
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Joint pain (arthropathy) – Deposits of xanthine crystals around joints can lead to pain, stiffness, or swelling in some patients, although this is less common than kidney problems.
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Muscle pain (myositis) – Xanthine can also collect in muscle tissue and cause muscle pain, tenderness, or weakness in a small number of patients with type 2 xanthinuria.
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Abdominal discomfort – General tummy pain or discomfort may come from stones, infections, or muscle strain related to repeated pain episodes, and may be the symptom that brings a patient to medical attention.
Diagnostic tests
Doctors usually follow a step-by-step plan to diagnose hereditary xanthinuria type 2. First, they look for the pattern of very low uric acid and high xanthine in blood and urine. Next, they confirm that the problem is hereditary xanthinuria and then identify whether it is type 1 or type 2, often using specialized biochemical and genetic tests.
Physical examination tests
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General physical examination – The doctor checks overall health, body weight, growth in children, signs of dehydration, and any visible swelling (edema) that might suggest kidney problems. They also look for tenderness, pain behaviours, and movement limits that may point to stone attacks or muscle pain.
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Abdominal and flank examination – The doctor gently presses (palpates) the abdomen and side areas over the kidneys to look for pain, guarding, or swelling. Pain in these areas can suggest kidney stones or infection related to xanthine buildup.
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Blood pressure measurement – High blood pressure can be a sign of chronic kidney disease. Regular blood pressure checks help doctors see if xanthine stones have started to damage kidney function over time.
Manual tests
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Costovertebral angle (CVA) tenderness test – The doctor taps gently over the area where the ribs meet the spine. Sharp pain in this area suggests kidney inflammation or stones, which are common complications in hereditary xanthinuria.
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Manual bladder palpation – By feeling above the pubic bone, the doctor checks whether the bladder is very full, which might happen if stones block urine flow. A full, tender bladder can guide further urgent tests.
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Pain scoring and palpation along the ureter path – Gentle pressure is applied along the usual path of the ureters in the abdomen to see where pain is strongest. This manual test helps localize where a stone might be stuck.
Laboratory and pathological tests
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Serum uric acid level – Blood is tested for uric acid. In hereditary xanthinuria, especially type 2, uric acid is very low or sometimes almost undetectable, which is one of the main clues that the purine pathway is blocked.
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Serum xanthine and hypoxanthine measurement – Special laboratory methods (such as high-performance liquid chromatography) measure xanthine and hypoxanthine in blood. In xanthinuria, these substances are high and help confirm the diagnosis.
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Urinalysis (routine urine test) – A simple urine test can show blood, crystals, infection signs, and sometimes xanthine crystals. Xanthine crystals can look different from common uric acid crystals and help point to this rare disease.
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24-hour urine study for purine metabolites – Collecting all urine for 24 hours lets the lab measure total xanthine, hypoxanthine, and uric acid. A pattern of very high xanthine and very low uric acid supports hereditary xanthinuria.
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Stone analysis (if stones are passed or removed) – When a stone is collected after passing or surgery, the lab can analyze its composition. Finding stones that are mainly made of xanthine (rather than calcium or uric acid) is a key diagnostic feature.
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Serum creatinine and urea (kidney function tests) – These blood tests show how well the kidneys are filtering waste. High levels suggest kidney damage, which can happen after years of stone disease in hereditary xanthinuria.
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Liver function tests – Because the enzymes involved are also expressed in the liver, doctors may check liver enzymes and overall liver health, and to rule out other metabolic diseases that can also give low uric acid.
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Genetic testing for MOCOS mutations – A blood or saliva sample is used to read the DNA sequence of the MOCOS gene. Finding two disease-causing mutations confirms hereditary xanthinuria type 2 and helps distinguish it from type 1 and other conditions.
Electrodiagnostic tests
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Electrocardiogram (ECG) – An ECG records the heart’s electrical activity. It is not specific for xanthinuria, but it may be done in patients with advanced kidney failure, because changed blood salts can disturb heart rhythm.
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Electromyography (EMG) for muscle symptoms – In the few patients who develop muscle pain or suspected myositis from xanthine deposits, EMG can be used to check how muscles and the nerves that control them are working, and to rule out other muscle diseases.
Imaging tests
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Renal and bladder ultrasound – Ultrasound uses sound waves to create images of the kidneys and bladder. It can show stones, blockage, swelling (hydronephrosis), or changes in kidney size without radiation, so it is often the first imaging test used.
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Non-contrast CT scan of kidneys, ureters, and bladder (CT KUB) – CT scanning makes very detailed pictures and is very good at finding stones and blockages. Xanthine stones can be less dense than some other stones, but CT still detects them better than plain X-rays.
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Intravenous urography (IVU) or contrast urography – In this older test, contrast dye is injected into a vein and X-rays are taken as the dye passes through the kidneys and urinary tract. It can outline areas where the flow is blocked by stones. It is used less often now but may still help in some settings.
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Nuclear renography (kidney isotope scan) – A small amount of radioactive tracer is injected, and special cameras track how well each kidney takes up and clears the tracer. This test measures kidney function in each kidney separately, which is helpful when stones affect one kidney more than the other.
Non-pharmacological treatments (therapies and other measures)
1. High fluid intake
Drinking plenty of water all day is the core non-drug treatment for hereditary xanthinuria type 2. A high fluid intake increases urine volume, which lowers the concentration of xanthine in the urine and helps prevent crystals and stones from forming. Doctors usually recommend spreading fluid intake across the day and evening, and increasing it in hot weather or during illness. The exact fluid target should be set by a specialist, but the aim is to maintain clear, light-colored urine and protect the kidneys.
2. Low-purine diet
A low-purine diet is strongly recommended because purines are broken down into hypoxanthine and xanthine in the body. By reducing purine intake, the body produces less xanthine, which lowers the risk of stone formation. Patients are advised to reduce or avoid organ meats, certain fish and shellfish, meat extracts, and large portions of red meat. Instead, they can emphasize fruits, vegetables, whole grains, and moderate amounts of low-purine proteins. Dietitians can design a balanced plan that fits the person’s age, culture, and other medical conditions.
3. Avoiding dehydration and overheating
Dehydration concentrates xanthine in the urine and makes crystal and stone formation more likely. Patients with hereditary xanthinuria type 2 should be careful in hot climates, during fever, vomiting, diarrhea, or heavy exercise. They may need to drink extra fluids or use oral rehydration solutions during these times. Avoiding prolonged exposure to extreme heat and ensuring regular rest and fluid breaks can be protective for the kidneys. This simple lifestyle strategy is an important part of long-term prevention.
4. Moderation of vigorous exercise
Very heavy or prolonged exercise can increase muscle breakdown and may promote crystal deposition in muscle, leading to pain or cramps in people with high xanthine levels. While normal physical activity is healthy and encouraged, extremely intense workouts or endurance sports may need to be limited or done with careful hydration. A doctor or physiotherapist can help design a safe exercise plan that supports general health without over-stressing the kidneys or muscles.
5. Regular kidney monitoring
Regular follow-up with ultrasound or other imaging is important to detect stones early in hereditary xanthinuria type 2. Imaging can show xanthine stones, kidney size, and any signs of obstruction. Early detection allows doctors to adjust diet and hydration, and to plan timely interventions if needed. Periodic blood tests for kidney function and urinalysis for blood, crystals, and infection also help to monitor disease status and guide treatment decisions.
6. Avoiding nephrotoxic drugs
Certain medicines, such as some painkillers, contrast dyes, and other nephrotoxic drugs, can further stress the kidneys. In a person whose kidneys are already at risk from xanthine stones, avoiding or minimizing these medicines is important. Doctors usually review all current medications and choose kidney-friendly options where possible. Patients should always inform healthcare providers that they have hereditary xanthinuria type 2 before receiving new medicines or imaging contrast.
7. Patient and family education
Education helps patients and families understand why hydration, diet, and regular monitoring matter. Clear explanations in simple language about the genetic cause, the risk of stones, and early warning signs of kidney problems can improve adherence. Written action plans, reminder apps, and follow-up calls can support daily habits. Genetic counseling can also explain recurrence risk in future pregnancies and options for carrier testing in relatives.
8. Genetic counseling
Because hereditary xanthinuria type 2 is autosomal recessive, each child of two carriers has a 25% chance of being affected. Genetic counseling provides information on inheritance patterns, carrier testing, and reproductive options. It can also help family members make informed choices about screening for kidney problems or testing for MOCOS variants when clinically appropriate. Counseling is especially helpful for couples planning pregnancies or families with multiple affected siblings.
9. Personalized nutrition counseling
A registered dietitian with experience in kidney or metabolic diseases can tailor the low-purine, kidney-friendly plan to the patient’s age, preferences, and other conditions such as diabetes or hypertension. This may include setting safe protein targets, planning meals for school or work, and managing cultural or religious dietary practices. Regular follow-up helps adjust the plan as growth, weight, and lab values change over time.
10. Psychological and social support
Living with a rare inherited disease can cause anxiety, isolation, or fear about kidney health and the future. Psychological support, such as counseling or support groups for rare kidney diseases, can help patients and families cope. Social workers can assist with school accommodations, work issues, or financial support for medical care. Emotional well-being is an important part of overall management and can improve adherence to treatment.
(There are additional lifestyle strategies such as keeping a hydration diary, coordinating school or workplace water breaks, and rapid medical review during infections. These are usually personalized by the treating team and build on the core principles above.)
Drug treatments
Important: At present, no medicine is specifically approved to cure hereditary xanthinuria type 2. Medicines are used mainly to control pain, treat infections, prevent or manage certain types of stones, and protect kidney function. All doses below are general information from drug labels and must be individualized by a doctor, especially in children and teenagers.
1. Potassium citrate (example: Urocit-K)
Potassium citrate is a citrate salt used to prevent certain calcium and uric-acid kidney stones by increasing urinary citrate and raising urine pH. Typical adult doses are divided through the day; exact dosing is based on urinary citrate and kidney function. In hereditary xanthinuria type 2, xanthine solubility does not improve much with alkalinization, so benefit is uncertain, but potassium citrate may be considered if other stone types or hypocitraturia are present. Side effects include stomach upset and risk of high potassium, especially in kidney impairment.
2. Sodium bicarbonate
Sodium bicarbonate can increase urinary pH and is sometimes used in kidney stone patients to reduce uric acid crystallization. In hereditary xanthinuria, several case reports describe its use as part of a broader regimen with low-purine diet and high fluids, although benefit for xanthine solubility is limited. Dosing is individualized, and excess use can cause metabolic alkalosis, fluid overload, or high sodium levels. Because evidence is weak, sodium bicarbonate should be used only under strict nephrology guidance.
3. Ibuprofen
Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) commonly used to relieve pain and reduce fever. In hereditary xanthinuria type 2, ibuprofen may be used short-term for mild to moderate pain, including flank pain from stones. The usual over-the-counter adult dose is 200–400 mg every 4–6 hours, with a maximum daily limit, but dosing must be adjusted in children and in kidney disease. NSAIDs can themselves damage the kidneys, especially with prolonged use, so they must be used at the lowest effective dose for the shortest possible time.
4. Acetaminophen (paracetamol)
Acetaminophen is a pain and fever medicine that does not have the same anti-inflammatory effects as NSAIDs but is gentler on the kidneys when used correctly. It can be useful for mild pain in hereditary xanthinuria, especially when avoiding NSAIDs is preferred. Standard adult doses are typically 325–1,000 mg every 4–6 hours, up to a daily maximum, but must be lower in liver disease and in children. Overdose can cause severe liver damage, and rare but serious skin reactions have been reported, so label instructions and doctor advice must be followed.
5. Antibiotics for urinary tract infections
Patients with xanthine stones are at higher risk of urinary tract infections because stones can obstruct urine flow and harbor bacteria. When symptomatic infection occurs (burning urination, fever, flank pain), doctors prescribe antibiotics based on local guidelines and urine culture results. Typical choices include drugs such as nitrofurantoin, trimethoprim-sulfamethoxazole, or cephalosporins, but the exact drug, dose, and duration depend on age, kidney function, and bacterial resistance patterns. Proper treatment of infections helps prevent kidney damage and sepsis.
6. Antispasmodic and anti-colic medicines
During acute stone passage, smooth muscle spasm in the ureter can cause severe cramping pain. Doctors sometimes use antispasmodic medicines to relax the urinary tract and ease colic symptoms. These drugs are selected from standard antispasmodic classes and are usually given for short periods only. Side effects may include dry mouth, blurred vision, and constipation. They are supportive agents and do not treat the underlying xanthine excess.
7. Intravenous fluids in hospital
When a patient with hereditary xanthinuria type 2 is admitted with severe pain, infection, or dehydration, intravenous fluids may be given to rapidly increase urine output and support blood pressure. The type and rate of fluid are carefully chosen by the medical team based on blood tests and vital signs. IV fluids are not a “drug” in the usual sense but are an important medical treatment to protect the kidneys in acute situations.
8. Medications for blood pressure and kidney protection (if needed)
If chronic kidney disease develops due to repeated stones or scarring, doctors may prescribe medicines such as ACE inhibitors or ARBs to control blood pressure and protect remaining kidney function. These drugs are widely used in kidney disease, but they must be started and monitored by a nephrologist, especially in young patients. They are not specific to hereditary xanthinuria type 2 but can help limit further damage once chronic kidney disease is present.
(Because there is no specific FDA-approved drug that corrects the MOCOS defect in hereditary xanthinuria type 2, additional “drug treatments” beyond these general categories would not be evidence-based. Experimental approaches, including enzyme or gene therapy, are still at research stage and are not standard of care.)
Dietary molecular supplements
There are no dietary supplements proven to directly correct hereditary xanthinuria type 2, but some nutritional strategies may support kidney and general health. All supplements should be discussed with a doctor, especially in people with kidney disease.
1. Balanced electrolyte oral hydration solutions
Oral rehydration solutions or electrolyte drinks, used appropriately, can help maintain fluid and salt balance during illness or hot weather. They support the main strategy of high urine volume while preventing low sodium or other imbalances. However, many commercial drinks contain sugar or excess sodium, so choice and amount should be guided by a clinician or dietitian.
2. Plant-based protein emphasis
Choosing more plant-based protein (such as beans, lentils, and tofu) and less animal organ meat and certain fish may lower purine intake and support kidney health. While not a supplement pill, this is a “molecular” nutrition approach that focuses on the composition of the diet to reduce purine load. A dietitian can help ensure enough essential amino acids while keeping purines low.
3. Omega-3 fatty acids from food
Omega-3 fatty acids, found in flaxseed, chia, and some fish, may have general anti-inflammatory and cardiovascular benefits. For patients with hereditary xanthinuria type 2 who also have cardiovascular risk factors, including modest amounts of omega-3–rich foods may support overall health. However, very high fish intake can increase purines, so the plan must balance benefits and purine content.
4. Antioxidant-rich fruits and vegetables
Fruits and vegetables that are rich in antioxidants (such as berries, citrus, leafy greens, and peppers) may support vascular and kidney health indirectly by reducing oxidative stress. They are typically low in purines and high in fiber, vitamins, and minerals. Patients should still avoid excessive grapefruit if taking certain medicines that interact with it.
5. Magnesium-rich foods
Magnesium from foods such as nuts, seeds, and whole grains may help prevent some types of kidney stones by influencing crystallization, although specific data for xanthine stones are limited. Since nuts and seeds have variable purine content, a dietitian can help choose types and portions that are safe within a low-purine pattern.
(Other supplements—such as high-dose vitamin C or unregulated “kidney detox” products—may be risky and are not recommended without specialist advice.)
Immunity-booster, regenerative, and stem cell drugs
At present, there are no approved “immunity-booster” medicines, regenerative drugs, or stem cell therapies specifically for hereditary xanthinuria type 2. The disease is caused by a genetic enzyme defect in purine metabolism, not by immune failure or bone-marrow disease, so stem cell transplantation or immune-stimulating drugs are not standard therapy and could be harmful. Research in animals is exploring how loss of MOCOS affects metabolism and kidney injury, but clinical gene or cell-based treatments for humans are still experimental and only available in carefully controlled research settings.
Surgical and interventional treatments
1. Extracorporeal shock wave lithotripsy (ESWL)
ESWL uses focused ultrasound shock waves from outside the body to break kidney stones into smaller pieces that can pass more easily in urine. It may be used for suitable xanthine stones depending on size, number, and location. Success rates can vary with xanthine stones because of their physical properties, so the urologist will choose ESWL or other methods based on imaging and clinical status.
2. Ureteroscopy with laser lithotripsy
In ureteroscopy, a thin flexible scope is passed through the urethra and bladder into the ureter or kidney. Small instruments or laser fibers are used to break stones and remove fragments. This approach is useful for stones that are lodged in the ureter or that are not suitable for ESWL. It requires anesthesia, and risks include bleeding, infection, and ureter injury, but it can quickly relieve obstruction and pain.
3. Percutaneous nephrolithotomy (PCNL)
PCNL is a minimally invasive surgery for large or complex kidney stones. A small tract is created through the skin into the kidney, and a nephroscope is used to break and remove stones. For patients with hereditary xanthinuria type 2 and heavy stone burden, PCNL can be an effective way to clear much of the stone load and protect kidney function. It is usually reserved for more severe cases because it is more invasive than ureteroscopy or ESWL.
4. Open or laparoscopic pyelolithotomy
Pyelolithotomy is a surgical procedure where the surgeon opens the renal pelvis (part of the kidney collecting system) to remove stones directly. It may be chosen when other less invasive techniques are not suitable, or when very large or unusual stones are present. Modern practice often prefers endoscopic methods, but pyelolithotomy remains an important option, especially in resource-limited settings.
5. Nephrectomy (kidney removal) in end-stage damage
In very severe, late cases where a kidney is extensively damaged, nonfunctioning, and causing repeated infections or pain, nephrectomy may be considered. The aim is to remove a source of ongoing infection and symptoms. This is a last-line option and is avoided whenever possible by earlier detection and treatment of stones. After nephrectomy, protecting the remaining kidney with careful hydration and monitoring becomes even more important.
Prevention strategies
1. Lifelong high-fluid intake to maintain dilute urine and lower stone risk.
2. Strict low-purine diet with guidance from a dietitian to reduce xanthine production.
3. Early treatment of urinary infections to prevent scarring and kidney damage.
4. Avoidance of dehydration during fever, hot weather, and exercise.
5. Regular kidney imaging and lab tests to detect problems early.
6. Careful use of NSAIDs and other nephrotoxic drugs, only under medical advice.
7. Genetic counseling for families to understand recurrence risks and screening options.
8. Education about warning signs such as flank pain, blood in urine, or reduced urine output.
9. Coordination with schools and workplaces so the person can drink water freely and use toilets when needed.
10. Participation in rare disease registries or studies, where available, to improve knowledge and management over time.
When to see a doctor
People with hereditary xanthinuria type 2 should see a doctor or nephrologist regularly, even if they feel well, to monitor kidney function and adjust diet and hydration plans. Medical review is urgent if there is severe or sudden side or back pain, visible blood in the urine, burning urination, fever with chills, vomiting that limits fluid intake, or a marked drop in urine output. These may signal stone obstruction or infection, both of which can threaten kidney function and overall health if not treated quickly.
What to eat and what to avoid
What to eat (examples)
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Plenty of water and suitable low-sugar fluids throughout the day to keep urine dilute.
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Fruits and vegetables that are low in purines and rich in vitamins and antioxidants, such as apples, berries, carrots, cucumbers, and leafy greens.
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Whole grains like rice, oats, and whole-wheat bread in moderate portions for energy and fiber.
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Low-fat dairy products if tolerated, for calcium and protein with relatively low purine content.
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Moderate amounts of plant-based protein such as beans or lentils, adjusted by a dietitian to keep total purines low.
What to avoid or limit (examples)
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Organ meats like liver, kidney, and heart, which are very high in purines and can sharply increase xanthine load.
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Certain fish and shellfish (anchovies, sardines, mussels) and meat extracts or gravies, which are also rich in purines.
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Large portions of red meat and frequent processed meats, which increase both purine intake and cardiovascular risk.
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Sugary soft drinks and high-fructose beverages, which can worsen metabolic health and may indirectly harm the kidneys.
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Unregulated “kidney detox” or high-dose supplement products that are not evidence-based and may contain harmful ingredients for people with kidney risk.
FAQs
1. Is hereditary xanthinuria type 2 the same as gout?
No. In gout, uric acid is high and forms crystals in joints. In hereditary xanthinuria type 2, uric acid is very low and xanthine is high. The crystals and stones are mainly xanthine, and the main problems are kidney stones and kidney damage, not classic gout attacks.
2. How is hereditary xanthinuria type 2 diagnosed?
Diagnosis combines very low blood and urine uric acid, high xanthine and hypoxanthine in urine, absence of xanthine oxidase activity, and sometimes an allopurinol loading test to distinguish types I and II. Today, many centers confirm the diagnosis by genetic testing of the MOCOS gene.
3. Can someone with hereditary xanthinuria type 2 live a normal life?
Yes, many people—especially those diagnosed early, who follow a low-purine diet and maintain high fluid intake—can live a near-normal life. Some remain symptom-free, while others have episodes of stones or kidney problems that need treatment. Regular monitoring is important to protect long-term kidney function.
4. Is there any cure or enzyme replacement therapy?
Currently there is no enzyme replacement, gene therapy, or curative drug for hereditary xanthinuria type 2. Treatment focuses on lifestyle changes and managing complications. Research on how MOCOS deficiency affects metabolism may someday support new therapies, but these approaches are still experimental.
5. Are xanthine oxidase inhibitors like allopurinol useful?
No. Drugs such as allopurinol are used to treat high uric acid by blocking xanthine oxidase, but in hereditary xanthinuria type 2 that enzyme is already inactive. Using these drugs can worsen xanthine accumulation and risk of stones and is therefore contraindicated.
6. Can children be screened if a parent has hereditary xanthinuria type 2?
Yes, children in affected families can be screened using blood and urine tests for uric acid and xanthine, and confirmed with genetic testing if indicated. Early diagnosis allows timely dietary advice and hydration strategies to prevent stones before symptoms appear.
7. Does everyone with hereditary xanthinuria type 2 develop kidney failure?
No. Many people never develop kidney failure, especially with early diagnosis and good preventive care. However, repeated stones, infections, or long-standing obstruction can lead to chronic kidney disease or, rarely, end-stage kidney failure if not managed.
8. How often should a person with hereditary xanthinuria type 2 see a doctor?
Frequency depends on age, kidney function, and past stone history. In general, regular visits (for example once or twice a year) to a nephrologist or metabolic specialist, plus extra visits when symptoms occur, are recommended to monitor labs, imaging, diet, and hydration practices.
9. Can pregnancy be safe in hereditary xanthinuria type 2?
Many women with hereditary xanthinuria type 2 can have successful pregnancies, but they need close monitoring of kidney function, hydration, and blood pressure. Some pain medicines and imaging tests are limited in pregnancy, so care must be coordinated between obstetricians and kidney specialists. Pre-pregnancy counseling is important.
10. Is hereditary xanthinuria type 2 common in any particular population?
Hereditary xanthinuria overall is extremely rare worldwide, with only a few hundred cases reported. Cases have been described in many regions, including Europe, Asia, and North Africa, but there is no single well-defined “high-risk” ethnic group. Because it is autosomal recessive, it may be more frequent in populations with higher rates of consanguinity.
11. Can herbal remedies cure hereditary xanthinuria type 2?
No herbal product has been proven to cure hereditary xanthinuria type 2 or to safely dissolve xanthine stones. Some herbal remedies may be harmful to the kidneys or interact with prescribed medicines. Patients should always discuss any herbal or traditional products with their doctor before use.
12. What is the difference between type 1 and type 2 hereditary xanthinuria?
Both types lead to high xanthine and low uric acid, causing similar symptoms. Type 1 is due to defects in the xanthine dehydrogenase gene, while type 2 is due to MOCOS defects and involves combined deficiency of xanthine dehydrogenase and aldehyde oxidase. Specialized biochemical tests or genetic testing are needed to distinguish them.
13. How is hereditary xanthinuria type 2 different from other purine metabolic disorders?
Other purine disorders, such as Lesch–Nyhan syndrome, usually cause very high uric acid and severe neurological symptoms. Hereditary xanthinuria type 2 mainly affects the kidney and urinary tract, with very low uric acid and xanthine stones but without the same neurological features. Understanding this difference helps focus management on kidney protection.
14. Can diet alone control hereditary xanthinuria type 2?
For many patients, a carefully planned low-purine diet plus high fluid intake is enough to significantly reduce stone episodes. However, some people still develop stones or infections and may need medicines or procedures. Diet is the foundation, but regular monitoring and flexible treatment plans are essential.
15. Where can families find more information and support?
Families can seek information from rare disease networks, kidney foundations, and trusted medical resources on hereditary xanthinuria and related metabolic disorders. Genetic counselors and nephrologists can direct patients to patient-friendly materials, clinical trials, and support groups that connect families facing similar challenges.
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.
