Xanthine Oxidase–Sulfite Oxidase Deficiency

Xanthine oxidase–sulfite oxidase deficiency is a very rare, serious genetic disease. In this condition, two important enzymes in the body, xanthine oxidase (also called xanthine dehydrogenase) and sulfite oxidase, do not work properly or are almost completely missing. These enzymes normally help break down certain proteins and waste products in the body. When they do not work, harmful chemicals such as sulfite and xanthine build up in the blood, brain, and other organs. This build-up can damage the brain, eyes, kidneys, and other tissues, especially in newborn babies and young children. [1]

Most of the time, this combined deficiency happens because the body cannot make a tiny helper molecule called the molybdenum cofactor. This cofactor is needed for several enzymes, including sulfite oxidase and xanthine dehydrogenase/oxidase, to work normally. Without this cofactor, both enzymes become inactive, so the baby shows signs of both sulfite oxidase deficiency and xanthine oxidase deficiency at the same time. [2]

Xanthine oxidase–sulfite oxidase deficiency usually refers to molybdenum cofactor deficiency (MoCD), a very rare genetic disease where the body cannot make a small helper molecule called the molybdenum cofactor. This cofactor is needed for several enzymes, including sulfite oxidase and xanthine oxidase (xanthine dehydrogenase). When these enzymes do not work, harmful chemicals such as sulfite and xanthine build up, especially in the brain, causing severe seizures, feeding problems, developmental delay, and often early death if untreated. [1]

There are types of MoCD (A, B, C) depending on which gene is affected. In type A, a specific drug called fosdenopterin (Nulibry) can replace the missing precursor of the cofactor and can lower the risk of death if started early. For other types and for isolated sulfite oxidase deficiency, treatment is mainly supportive: controlling seizures, protecting nutrition, preventing infections, and providing palliative care. [2]

This disease is inherited in an autosomal recessive way. This means that a child becomes sick only when they receive one non-working gene from each parent. Parents usually have no symptoms themselves. The disease often appears soon after birth with difficult-to-control seizures and rapid brain damage, and sadly, many affected babies become very sick very quickly. [3]

Other Names

Doctors and researchers use several different names for xanthine oxidase–sulfite oxidase deficiency. These names may appear in medical books or reports: [5]

• Combined deficiency of sulfite oxidase and xanthine oxidase

• Combined deficiency of sulfite oxidase and xanthine dehydrogenase

• Combined xanthine oxidase–sulfite oxidase defect

• Inborn error of molybdenum metabolism with sulfite oxidase and xanthine oxidase deficiency

• Molybdenum cofactor–related sulfite oxidase and xanthine dehydrogenase deficiency

• Sulfite oxidase deficiency due to molybdenum cofactor deficiency (a broader term that also includes xanthine enzyme problems)

• Encephalopathy due to sulfite oxidase and xanthine oxidase deficiency

• Neurometabolic disease due to molybdenum cofactor deficiency (with xanthine and sulfite oxidase defect)

These names all describe the same basic problem: both enzymes that need the molybdenum cofactor are not working well in the same patient. [6]

Types

Doctors often talk about types based on which gene is changed and how the molybdenum cofactor pathway is affected. The combined xanthine oxidase–sulfite oxidase deficiency usually sits inside the larger group called molybdenum cofactor deficiency (MoCD). [7]

• Type A MoCD – due to changes in the MOCS1 gene. This is the most common type. It often causes very early and severe disease with both sulfite oxidase and xanthine oxidase deficiency. [8]

• Type B MoCD – due to changes in the MOCS2 gene. It also leads to loss of the molybdenum cofactor and combined enzyme deficiency, with symptoms very similar to type A. [9]

• Type C MoCD – due to changes in the GPHN gene (gephyrin). This gene helps to attach the molybdenum atom to the cofactor. When it is not working, several molybdenum-dependent enzymes, including sulfite oxidase and xanthine dehydrogenase, are affected. [10]

• Very rare combined enzyme defects with unclear gene or cofactor steps – a few older case reports describe combined sulfite oxidase and xanthine oxidase deficiency where the detailed gene defect was not yet known, but molybdenum cofactor synthesis was suspected. [11]

In practice, when both sulfite oxidase and xanthine oxidase are missing, doctors usually classify the child under molybdenum cofactor deficiency and then state that both enzymes are deficient. [12]

Causes

Here, “causes” means the direct genetic reasons and also the main risk factors that increase the chance of this disease. [13]

1. MOCS1 gene variants (MoCD type A)
   Harmful (pathogenic) changes in the MOCS1 gene stop the first step of molybdenum cofactor production. Without this step, the body cannot finish making the cofactor, and both sulfite oxidase and xanthine dehydrogenase become inactive. [14]

2. MOCS2 gene variants (MoCD type B)
   Changes in the MOCS2 gene block later steps in cofactor synthesis. This again leads to no usable molybdenum cofactor. As a result, sulfite oxidase and xanthine oxidase/dehydrogenase lose their activity, leading to the combined deficiency. [15]

3. GPHN gene variants (MoCD type C)
   GPHN (gephyrin) helps attach the molybdenum atom to the pterin backbone. Pathogenic variants in GPHN prevent final assembly of the cofactor, causing failure of several molybdenum-dependent enzymes, including sulfite oxidase and xanthine dehydrogenase. [16]

4. Other very rare genes in the cofactor pathway
   Some patients have clinical and biochemical signs of MoCD but no changes in the known genes. Researchers suspect there may be extra, very rare genes in the molybdenum cofactor pathway that can also cause combined enzyme deficiency. [17]

5. Autosomal recessive inheritance pattern
   The disease occurs when a child inherits one non-working copy of the gene from each parent. Having only one non-working copy usually does not cause symptoms, but having two leads to full enzyme deficiency. This inheritance pattern explains why the disease often appears in siblings but not in parents. [18]

6. Parental consanguinity (parents related by blood)
   When parents are cousins or closely related, they are more likely to share the same rare pathogenic variant. This increases the chance that their child will inherit two copies and develop the combined deficiency. [19]

7. Family history of molybdenum cofactor deficiency or sulfite oxidase deficiency
   If an older child or relative has MoCD or isolated sulfite oxidase deficiency, future babies in the family have a higher risk of also having the combined defect, especially if the parents are known carriers. [20]

8. Carrying pathogenic variants in MOCS1
   Parents who carry one faulty MOCS1 gene are healthy but have a 25% chance in each pregnancy of having an affected child if their partner carries the same variant. Being a carrier is therefore an important part of the causal chain. [21]

9. Carrying pathogenic variants in MOCS2
   The same logic applies to MOCS2: two carriers of the same harmful MOCS2 variant have a one-in-four chance in each pregnancy of having a child with MoCD type B and combined enzyme deficiency. [22]

10. Carrying pathogenic variants in GPHN
    When both parents carry a non-working GPHN gene, their baby can develop MoCD type C with both sulfite oxidase and xanthine dehydrogenase deficiency. Genetic carrier status is therefore a key underlying cause. [23]

11. Defect in early fetal brain protection from sulfite
    In affected fetuses, sulfite and related molecules may build up before birth, damaging the developing brain. While this is a consequence, not a separate genetic cause, it is part of how the gene defect leads to the clinical disease. [24]

12. Defect in purine metabolism via xanthine dehydrogenase
    Lack of xanthine dehydrogenase leads to high xanthine and low uric acid levels in blood and urine. This biochemical imbalance can form crystals or stones and may damage kidneys, which is an important downstream effect of the primary genetic cause. [25]

13. Reduced activity of other molybdenum-dependent enzymes (like aldehyde oxidase)
    In many MoCD patients, aldehyde oxidase and related enzymes are also affected. While these are not direct causes on their own, their low activity worsens the overall toxicity picture caused by the basic gene defects. [26]

14. Biochemical accumulation of sulfite and S-sulfocysteine
    Because sulfite oxidase is missing, sulfite and S-sulfocysteine accumulate. These chemicals are directly toxic to neurons and are important intermediates between the gene defect and brain damage. [27]

15. Biochemical accumulation of xanthine and hypoxanthine
    Without xanthine oxidase/dehydrogenase, xanthine and hypoxanthine build up. Over time, they can crystallize in the kidneys and urinary tract, causing stones and kidney problems, which contribute to the clinical picture. [28]

16. Lack of normal uric acid production
    Low serum and urine uric acid are a direct result of xanthine dehydrogenase deficiency. While uric acid itself is a waste product, its absence is a key sign that the enzyme is not working and helps doctors connect the genetic cause to the patient’s lab results. [29]

17. Genetic changes present in all cells from conception
    The pathogenic variants are present from the moment of conception in every cell, so the disease process can begin before birth. This explains why many babies show signs immediately after delivery. [30]

18. Lack of effective natural repair or bypass pathways
    The body has no good backup system for the molybdenum cofactor pathway. When this pathway fails, there is no easy way to restore sulfite oxidase or xanthine dehydrogenase function, so the gene defect strongly and directly causes disease. [31]

19. No environmental cure for the enzyme defect
    Ordinary diet, vitamins, or minerals cannot fix the missing molybdenum cofactor in classic forms of the disease. This means the genetic cause dominates over any lifestyle factor. [32]

20. Rare but possible secondary or acquired blocks of the cofactor pathway
    Experimental work in animals shows that certain metals such as tungsten can block molybdenum enzymes. In humans, this is not a usual cause, but it helps explain how strongly the cofactor system controls sulfite oxidase and xanthine oxidase activity. [33]

Symptoms

Symptoms usually begin in the first hours or days after birth and progress very quickly. Severity can vary, but most classic cases are extremely serious. [34]

1. Early-onset seizures
   Many babies develop seizures within the first hours or days of life. The seizures may be frequent and difficult to control with usual medicines. These seizures happen because toxic sulfite and related compounds irritate and damage brain cells. [35]

2. Feeding difficulties
   Affected newborns often have trouble sucking and swallowing. They may choke, cough, or take a very long time to feed. This is due to poor muscle control and brain injury affecting the nerves that control feeding. [36]

3. Progressive encephalopathy (worsening brain function)
   Over days to weeks, the baby may become less alert, less responsive, and more floppy or stiff. This gradual loss of brain function is called encephalopathy and is a key feature of sulfite oxidase deficiency and MoCD. [37]

4. Abnormal muscle tone (hypotonia or spasticity)
   Some babies feel very floppy (low tone), while others become very stiff with tight muscles (spasticity). Many children show a mixture of both at different times. This happens because of damage to brain areas that control movement. [38]

5. Developmental delay
   As the child grows, they may not reach milestones such as holding up the head, rolling, sitting, or talking. Severe forms can cause profound developmental delay or lack of progress after an early period of illness. [39]

6. Microcephaly (small head size)
   The head may be small at birth or may grow more slowly than the rest of the body. This is called microcephaly and reflects loss of brain tissue or poor brain growth from the toxic effects of sulfite and related compounds. [40]

7. Abnormal movements and postures
   Babies may show arching of the back, stiff extended limbs, or unusual postures called opisthotonus. These postures are signs of serious brain and muscle control problems. [41]

8. Lens dislocation (ectopia lentis)
   In many children with sulfite oxidase deficiency and MoCD, the clear lens in the eye slips out of its normal position. This is called ectopia lentis and can cause poor vision or blindness if not recognized. [42]

9. Abnormal facial features in some patients
   Some babies develop coarse or unusual facial features over time, such as deep-set eyes, a broad nose, or a small chin. These features are not always present, but when they are, they may reflect long-standing brain and bone changes. [43]

10. Irritability and unexplained crying
    Babies can be very irritable, cry excessively, or seem uncomfortable. This may be due to pain from seizures, muscle stiffness, or kidney stones caused by excess xanthine. [44]

11. Poor growth (failure to thrive)
    Because of feeding problems and severe illness, many children do not gain weight or grow normally. They may need tube feeding or special nutritional support. [45]

12. Kidney stones and kidney problems (in some survivors)
    When xanthine levels are very high, crystals can form stones in the kidneys and urinary tract. This can cause blood in the urine, pain, or kidney damage, especially in cases where the child lives longer. [46]

13. Abnormal breathing or apnea
    Brain damage can affect the centers that control breathing. Some babies have irregular breathing, pauses in breathing (apnea), or need respiratory support. [47]

14. Profound intellectual disability in survivors
    Children who live beyond infancy, especially with severe early disease, often have very limited understanding, communication, and motor skills due to extensive brain injury. [48]

15. High risk of early death without treatment
    Sadly, classic forms of molybdenum cofactor deficiency with combined sulfite oxidase and xanthine oxidase deficiency often lead to death in infancy or early childhood, especially without early diagnosis and any available specific treatment (such as cPMP replacement in suitable type A cases). [49]

Diagnostic Tests

Physical Examination

1. Full newborn and child physical examination
   The doctor performs a head-to-toe exam, checking skin color, breathing, heart rate, reflexes, and general responsiveness. In xanthine oxidase–sulfite oxidase deficiency, the exam may show a very sick baby with seizures, poor feeding, abnormal tone, and signs of brain injury. This exam guides which urgent tests are needed next. [50]

2. Growth measurement (weight, length, head size)
   The doctor measures weight, length, and head circumference and plots them on growth charts. A small head or slow head growth can suggest brain injury from sulfite build-up, while poor weight gain may show feeding and metabolic problems. [51]

3. Detailed neurological examination
   The doctor checks muscle tone, reflexes, posture, and movement patterns. Findings such as spasticity, opisthotonus, poor head control, or absent reflexes are common in this disease and support the suspicion of a severe neurometabolic disorder. [52]

4. Eye and lens examination
   Using a light and sometimes special equipment, the doctor examines the eyes and lens position. Detecting lens dislocation (ectopia lentis) in a baby with seizures and developmental problems is a strong clue for sulfite oxidase or molybdenum cofactor deficiency. [53]

Manual and Bedside Tests

5. Assessment of feeding and swallowing
   Nurses and doctors watch the baby feeding and may gently test sucking and swallowing reflexes. Poor sucking, choking, or failure to coordinate breathing and swallowing suggest neurological disease and help direct further metabolic testing. [54]

6. Developmental milestone assessment
   Over time, therapists and doctors assess whether the child can hold up their head, roll, sit, or respond to sounds and faces. Delay or loss of milestones supports the diagnosis of a progressive brain disorder such as MoCD. [55]

7. Simple vision and hearing response tests
   Clinicians may check whether the baby follows a light, reacts to noise, or startles to sound. Reduced responses can be due to cortical brain damage from sulfite toxicity and guide decisions for more advanced tests. [56]

8. Pain and sensation response testing
   Gentle stimulation, such as a light pinch, is used to see if the baby reacts normally. Abnormal or reduced responses can signal severe central nervous system injury linked to the combined enzyme deficiency. [57]

Laboratory and Pathological Tests

9. Urine sulfite screening (dipstick or special test)
   A simple urine test can detect high levels of sulfite. Persistent positive sulfite in urine is a strong sign of sulfite oxidase deficiency or molybdenum cofactor deficiency and is often one of the first laboratory clues. [58]

10. Urine S-sulfocysteine and thiosulfate measurement
    More detailed urine tests in a metabolic laboratory measure S-sulfocysteine and thiosulfate. High levels of these compounds are characteristic for sulfite oxidase deficiency and MoCD and help confirm the biochemical diagnosis. [59]

11. Plasma and urine amino acid analysis
    Specialized testing of amino acids can show abnormal patterns related to sulfur-containing amino acids in this disease. These patterns, together with high sulfite markers, support the diagnosis of combined sulfite oxidase and xanthine oxidase deficiency. [60]

12. Serum uric acid level
    In many patients with combined deficiency, the blood uric acid level is very low because xanthine dehydrogenase cannot convert xanthine to uric acid. A very low uric acid level in a sick infant is a key biochemical sign of MoCD. [61]

13. Urine purine and pyrimidine analysis (xanthine and hypoxanthine)
    A urine test can measure xanthine and hypoxanthine. High levels of these compounds, together with low uric acid, show that xanthine dehydrogenase is not working, pointing to a purine metabolism defect within the MoCD spectrum. [62]

14. Measurement of enzyme activity in fibroblasts or liver tissue
    In specialized centers, doctors may measure sulfite oxidase and xanthine dehydrogenase activity in cultured skin cells or liver biopsy samples. Very low or absent activity of both enzymes confirms the combined deficiency at the enzyme level. [63]

15. Molybdenum cofactor or cPMP metabolite testing
    Some labs can measure intermediates of the molybdenum cofactor pathway, such as cyclic pyranopterin monophosphate (cPMP). Abnormal or missing metabolites help classify the exact type of MoCD and support the diagnosis. [64]

16. Molecular genetic testing (MOCS1, MOCS2, GPHN and related genes)
    DNA testing looks for pathogenic variants in known molybdenum cofactor genes. Finding disease-causing changes in MOCS1, MOCS2, or GPHN confirms the molecular basis of the combined xanthine oxidase–sulfite oxidase deficiency and allows carrier and prenatal testing in the family. [65]

17. Basic blood tests (complete blood count, serum electrolytes, liver and kidney function)
    Routine blood tests help assess the child’s overall condition. They may show dehydration, kidney problems, or other complications but are not specific. They are still important to monitor the effects of seizures, poor feeding, and kidney injury from xanthine stones. [66]

Electrodiagnostic Tests

18. Electroencephalogram (EEG)
    EEG records the electrical activity of the brain using small electrodes on the scalp. In this disease, EEG often shows a severely abnormal pattern with frequent epileptic sharp waves or a very low level of brain activity, confirming that the seizures come from serious brain dysfunction. [67]

19. Evoked potentials (visual or auditory)
    These tests measure how the brain responds to light flashes or sounds. Delayed or absent responses show that brain pathways are not working normally, which helps to document the severity of neurological damage caused by the combined enzyme deficiency. [68]

Imaging Tests

20. Brain MRI
    Magnetic resonance imaging (MRI) gives detailed pictures of the brain. In xanthine oxidase–sulfite oxidase deficiency and MoCD, MRI may show brain atrophy, white-matter changes, cystic areas, or other signs of severe metabolic encephalopathy. These findings, together with the biochemical tests, strongly support the diagnosis. [69]

21. Cranial ultrasound in newborns
    In very young babies, ultrasound through the soft spot (fontanelle) can quickly show bleeding, cysts, or early brain atrophy. While less detailed than MRI, it is useful as a first imaging test in unstable infants with seizures and suspected metabolic disease. [70]

22. Brain CT scan (if MRI is not available)
    Computed tomography (CT) can show loss of brain tissue, enlarged fluid spaces, or calcifications. It is faster than MRI but uses radiation. In resource-limited settings, CT may be the first advanced brain imaging test for a child with suspected MoCD. [71]

23. Kidney and urinary tract ultrasound
    Because xanthine levels can be high, some patients develop kidney stones. Ultrasound of the kidneys and bladder can detect these stones and any swelling (hydronephrosis). This helps doctors understand the impact of the xanthine oxidase deficiency component on the kidneys. [72]

Non-pharmacological treatments

(These are supportive strategies. They do not “cure” the enzyme problem but help reduce complications and improve comfort. Always guided by a metabolic / neurology specialist.)

1. Emergency seizure first-aid and safety education
   Families are taught how to protect the child during a seizure: gently laying them on their side, keeping the airway open, loosening tight clothes, timing the seizure, and knowing when to call emergency services. This training reduces the risk of choking, injury, and delayed care. Clear written plans and school or caregiver education are important, because seizures in MoCD and isolated sulfite oxidase deficiency are often frequent and hard to control. [3]

2. Intensive neonatal and pediatric neurologic care
   In early-onset disease, babies often need care in a neonatal or pediatric intensive care unit for monitoring breathing, heart rate, temperature, and seizures. Continuous EEG, oxygen, and ventilator support may be required. The goal is to stabilize the baby, manage seizures quickly, and prevent secondary brain injury from low oxygen, low blood sugar, or infections. [4]

3. Feeding support and speech/swallow therapy
   Because feeding difficulty is very common, a speech and swallow therapist assesses how safely the child can drink or eat. They may recommend special bottle nipples, thickened fluids, or feeding positions to lower the chance of aspiration (food going into the lungs). If oral feeding is not safe or not enough, tube feeding through a nasogastric tube or gastrostomy can provide reliable calories and prevent malnutrition. [5]

4. Low-sulfur amino acid / low-methionine diet trial
   Some centers try a diet that reduces methionine and sulfur-containing amino acids, sometimes with cysteine supplementation, to lower sulfite production. Evidence is limited and benefits may be short-term, but in some reports, seizure control and irritability improved temporarily. Any such diet must be supervised by a metabolic dietitian, because strong protein restriction can cause poor growth and new nutrient deficiencies. [6]

5. Hydration and kidney-friendly measures
   When xanthine oxidase is deficient (as in xanthinuria or MoCD), excess xanthine can crystallize and cause kidney stones in some patients. High fluid intake, regular urination, and sometimes mild urinary alkalinization can help limit stone formation. In practice, the metabolic team adjusts these measures according to urine chemistry and kidney ultrasound results. [7]

6. Physiotherapy to manage tone and contractures
   Children often have mixed low and high muscle tone, spasticity, and abnormal postures. Daily physiotherapy helps stretch tight muscles, improve joint movement, and prevent fixed contractures, which can cause pain and make care harder. Therapists may teach caregivers safe stretching routines and positioning techniques for home use. [8]

7. Occupational therapy and postural management
   Occupational therapists help with seating, head control, and daily care tasks. Custom seating systems, special cushions, and supports can improve comfort, reduce pressure sores, and make feeding and breathing safer. Proper posture also reduces the risk of aspiration and chest infections, which are common in severe neurodisability. [9]

8. Respiratory physiotherapy and airway clearance
   Because many children are immobile and have weak cough, mucus can build up in the lungs. Chest physiotherapy, suctioning when needed, and positioning therapy (like side-lying) help clear secretions. These measures lower the risk of pneumonia and hospital admissions and are standard in children with severe neurologic conditions. [10]

9. Vision assessment and management of lens problems
   Dislocation of the eye lens (ectopia lentis) has been reported in sulfite oxidase and MoCD patients. Regular eye exams allow early detection of lens dislocation, glaucoma, or retinal damage. Non-surgical measures like glasses, contact lenses, and low-vision aids may help some children use their remaining vision and interact better with their environment. [11]

10. Developmental and educational support
    A developmental pediatrician, special educator, and therapists assess abilities and help build an individualized education and stimulation plan. Even if a child has severe disability, early sensory stimulation, music, simple cause-and-effect toys, and consistent routines can improve comfort and communication with caregivers. [12]

11. Pain and comfort assessment using non-drug methods
    Children who cannot speak may show pain as irritability, unusual movements, or poor sleep. Simple comfort measures—positioning, gentle massage, warm baths, quiet environments, and predictable routines—help reduce distress. Palliative care teams often teach families to read their child’s signals and use non-drug comfort methods before or together with medications. [13]

12. Genetic counseling for the family
    Because MoCD and isolated sulfite oxidase deficiency are usually autosomal recessive, parents have a 25% chance of having another affected child with each pregnancy. Genetic counseling explains inheritance, carrier testing, prenatal diagnosis, and reproductive options so families can make informed decisions. [14]

13. Psychological and social support for caregivers
    Caring for a child with a severe, life-limiting metabolic disease is extremely stressful. Psychological counseling, social work support, and family or peer support groups help caregivers manage grief, anxiety, and burnout, and connect with resources such as respite care and financial help. [15]

14. Palliative care and advance care planning
    Because early-onset MoCD often has a poor prognosis, palliative care teams help families focus on comfort, dignity, and quality of life. They discuss options such as home-based care, limits of intensive care, symptom control plans, and preferred place of care near end of life. [16]

15. Infection-prevention lifestyle measures
    Good hand hygiene, up-to-date routine vaccinations, avoiding tobacco smoke, and limiting exposure to sick contacts help reduce respiratory infections, which can trigger seizures and hospitalizations in these fragile children. Influenza and pneumococcal vaccines are usually recommended according to national schedules. [17]

16. Regular kidney and urinary tract monitoring
    In patients with significant xanthine overproduction (xanthinuria spectrum), periodic urine tests and kidney ultrasound help detect stones early. Simple non-drug interventions such as hydration, prompt treatment of urinary infections, and nutrition adjustment are planned based on these findings. [18]

17. Nutritional optimization and micronutrient support
    Dietitians aim to keep calories, protein, vitamins, and minerals adequate while respecting any special metabolic restrictions. They monitor growth charts and blood tests and adjust tube feeds or formulas to prevent deficiencies in iron, vitamin D, calcium, and essential fatty acids. [19]

18. Sleep hygiene strategies
    Irregular sleep–wake cycles are common in children with severe brain injury. Day–night routines, light exposure during the day, quiet and dim lights at night, and consistent bedtime rituals can gently entrain a more predictable sleep pattern, which benefits both the child and caregivers. [20]

19. Assistive communication methods
    Some children may respond to simple signals, eye gaze, or switches. Speech and language therapists can introduce basic augmentative and alternative communication (AAC) tools—like picture boards or simple switches—that allow the child to express comfort, discomfort, or preferences as far as their abilities allow. [21]

20. Participation in registries and research follow-up
    Families may be invited to join disease registries or natural-history studies. This does not directly treat the child but can give access to expert centers and potential future trials, and helps researchers better understand outcomes and develop new therapies such as improved cofactor replacement or gene-based treatments. [22]

Drug treatments

Important: Doses, timing, and drug choices must always be set by a metabolic / neurology specialist. Information below is educational, based on FDA-approved labels and published experience, not a self-treatment guide.

1. Fosdenopterin (Nulibry) – substrate replacement therapy
   Fosdenopterin is a synthetic form of cyclic pyranopterin monophosphate (cPMP), a missing precursor in MoCD type A. It is given by intravenous infusion and supplies the building block needed to make the molybdenum cofactor. This can restore activity of sulfite oxidase and xanthine oxidase, lower toxic metabolites, and has been shown to reduce the risk of death when started early in life. Dose and schedule are weight-based according to the FDA label and must be handled in experienced centers. [23]

2. Levetiracetam (Keppra and generics) – antiseizure drug
   Levetiracetam is a broad-spectrum antiepileptic used very often in neonatal and pediatric seizures. It binds to the synaptic vesicle protein SV2A and helps stabilize electrical activity in the brain. It is available as oral solution and intravenous infusion; dosing is adjusted to weight and kidney function. Common side effects include sleepiness, irritability, and appetite changes. It is not specific for MoCD but is widely used to control seizures in these children. [24]

3. Phenobarbital – barbiturate antiseizure drug
   Phenobarbital enhances GABA-mediated inhibition in the brain and is one of the most commonly used drugs for neonatal seizures worldwide. In MoCD and sulfite oxidase deficiency, it may help reduce seizure frequency, although seizures often remain difficult to control. It is given orally or intravenously with dosing adjusted by level monitoring. Side effects include sedation, breathing suppression, low blood pressure, and long-term cognitive effects, so careful specialist supervision is essential. [25]

4. Diazepam – benzodiazepine rescue medicine
   Diazepam (Valium and injection/autoinjector forms) is used as a rescue medicine for acute, prolonged seizures or seizure clusters. It enhances GABA activity, calming overactive brain networks. It may be given rectally, intravenously, or through other routes depending on local practice. Side effects include drowsiness, breathing suppression, and risk of dependence with repeated use, so it is reserved for emergencies rather than daily seizure control. [26]

5. Midazolam – short-acting benzodiazepine for status epilepticus
   Midazolam is often used in intensive care for continuous or repeated seizures that do not respond to first-line drugs. It is given intravenously or sometimes buccally or intranasally. It acts quickly and strongly, but can depress breathing and blood pressure, so children need continuous monitoring in an ICU. It is not specific to MoCD but is part of general status epilepticus protocols. [27]

6. Other antiseizure medicines (valproate, topiramate, etc.) – individualized use
   Depending on the seizure type and EEG pattern, specialists may use drugs such as valproate, topiramate, lamotrigine, or others. Evidence in MoCD and sulfite oxidase deficiency is mostly from case reports and general neonatal seizure experience, not large trials. Every choice balances seizure control against side effects like liver toxicity, thrombocytopenia, or behavior changes. [28]

7. Baclofen – anti-spasticity muscle relaxant
   Baclofen is a GABA_B receptor agonist that reduces muscle stiffness and spasms. In children with severe spasticity from early brain injury, oral baclofen can improve comfort, ease hygiene care, and reduce painful contractures. Dose is slowly increased and adjusted for kidney function, as baclofen is cleared by the kidneys. Sudden withdrawal can cause seizures and high fever, so tapering is important. [29]

8. Clonazepam – benzodiazepine for chronic myoclonic seizures
   Clonazepam is sometimes used for myoclonic jerks and other difficult seizure types. It potentiates GABA and may reduce spasticity and startle. Sedation, drooling, and tolerance over time are common issues. Because benzodiazepines can cause dependence, specialists carefully review risks and benefits, especially in long-term use. [30]

9. Proton-pump inhibitors or H2-blockers – reflux control
   Children with severe neurologic disability often suffer from gastro-esophageal reflux, which can cause pain, feeding refusal, and aspiration into the lungs. Drugs like omeprazole (PPI) or ranitidine-like medicines (H2-blockers, where still in use) reduce stomach acid and help protect the esophagus. They are not specific to MoCD but are part of comprehensive symptom management. [31]

10. Laxatives and stool-softeners – constipation management
    Limited mobility, low fluid intake, and multiple drugs can cause severe constipation. Osmotic laxatives (for example, polyethylene glycol) and stool-softeners are used to keep stools soft and regular. This improves comfort, reduces abdominal pain, and can even make seizure behavior easier to interpret, because pain can trigger irritability and spasms. [32]

11. Antibiotics – treatment of infections
    Children with severe neurologic disability are prone to chest infections and urinary tract infections. Prompt, appropriate antibiotic therapy guided by culture results helps prevent sepsis, which can worsen seizures and accelerate clinical decline. Antibiotic choice follows local guidelines and infection type; it is not unique to this disorder. [33]

12. Vaccines – infection prevention
    Routine childhood vaccines (for example, against pneumococcus, influenza, pertussis) are critical to reduce serious infections. While vaccines are not “drugs for MoCD,” they indirectly improve survival and quality of life by preventing illnesses that could trigger severe seizures or respiratory failure. [34]

13. Analgesics and antipyretics (paracetamol, ibuprofen)
    Simple pain and fever medicines are important for comfort. Fever often worsens seizures, so controlling temperature during infections may indirectly reduce seizure burden. As always, dosing is strictly weight-based and kidney/liver function must be considered. [35]

14. Anti-spasticity alternatives (tizanidine, diazepam as muscle relaxant)
    In some children, drugs like tizanidine or low-dose diazepam may be used mainly for spasticity rather than seizures. They relax skeletal muscle but can cause sedation and low blood pressure, so close monitoring is needed. [36]

15. Antireflux prokinetic agents (where appropriate)
    In selected cases with severe reflux and poor gastric emptying, prokinetic drugs may be tried to improve motility. Evidence is limited and safety profiles vary, so these are used cautiously and often as a bridge to other interventions such as fundoplication if needed. [37]

16. Sedatives for procedures (short-acting benzodiazepines, etc.)
    Children with severe stiffness or frequent seizures sometimes need sedation for imaging, surgery, or dental care. Anesthesia teams choose drugs that are safest in the context of the child’s respiratory status and metabolic condition, usually short-acting benzodiazepines or other agents with careful monitoring. [38]

17. Vitamin and mineral supplements (when deficient)
    If blood tests show deficiencies (e.g., vitamin D, iron), standard supplements are prescribed. They do not correct the enzyme defect but support bone health, immunity, and energy. Supplement choice and dose follow regular pediatric guidelines. [39]

18. Cysteine supplementation (experimental diet adjunct)
    Some case reports suggest that adding cysteine while restricting methionine may partially bypass certain metabolic blocks and improve symptoms for short periods. This remains experimental and must be supervised within a specialist metabolic center because the overall protein balance is delicate in infants. [40]

19. Antispasticity pump therapies (intrathecal baclofen – highly selected)
    In older children with very severe spasticity, some centers consider intrathecal baclofen pumps. These devices deliver baclofen directly into the spinal fluid, giving more effect with less systemic exposure. Surgery and device care are complex, and experience in MoCD is extremely limited, so this is only considered case-by-case. [41]

20. Research / compassionate-use therapies
    Occasionally, families may access experimental treatments or compassionate-use drug programs, especially related to substrate replacement or gene-based therapies in MoCD type A. These are carefully controlled and monitored research settings, not routine clinical care. [42]

Dietary molecular supplements

These are general metabolic/nutritional supports. They are not substitutes for fosdenopterin where indicated. Exact products and doses are chosen by the metabolic dietitian and physician.

1. Specialized amino-acid formulas – provide controlled amounts of methionine and other amino acids while maintaining total protein needs. [43]

2. Essential fatty acid supplements (omega-3) – support brain and retinal cell membranes and general anti-inflammatory balance, especially if normal diet is limited. [44]

3. Vitamin D and calcium – protect bone density in non-ambulant children who have little weight-bearing and may take long-term antiseizure drugs affecting bone metabolism. [45]

4. Multivitamin preparations – ensure adequate intake of B-vitamins and trace elements when feeds are restricted or mainly formula-based. [46]

5. Iron supplementation – corrects iron deficiency anemia, improving energy and possibly reducing irritability and poor feeding. [47]

6. Cysteine-enriched blends (trial use) – used in some reports together with methionine restriction to modulate sulfur amino acid metabolism in MoCD; still experimental. [48]

7. Fiber supplements – help manage constipation when diet is limited and fluid intake is modest. [49]

8. Electrolyte solutions – used during illness to maintain fluid and salt balance and avoid dehydration that can worsen seizures. [50]

9. Probiotic preparations – sometimes used to support gut health during frequent antibiotic courses, though evidence in MoCD specifically is sparse. [51]

10. High-calorie modular supplements – concentrated calorie powders or liquids added to feeds to maintain growth when volume tolerance is low. [52]

Immunity-booster / regenerative / stem-cell-related drugs

1. Routine vaccines (indirect immunity booster)
   The most realistic “immunity booster” is simply staying up-to-date with routine vaccines and seasonal shots (like influenza). These do not fix the enzyme problem but reduce infections that can trigger status epilepticus and hospital stays. [53]

2. Standard infection prophylaxis (e.g., palivizumab where indicated)
   In some high-risk infants, monoclonal antibodies such as palivizumab may be used to reduce severe RSV infection risk, similar to other infants with severe neurologic disease. This is not specific to MoCD but is part of overall preventive care in selected cases. [54]

3. Fosdenopterin as “functional enzyme restoration”
   Although not a stem-cell drug, fosdenopterin effectively restores function of molybdenum-dependent enzymes in MoCD type A by supplying the missing cofactor precursor. This is a form of substrate replacement that partially normalizes metabolism and improves survival when given early. [55]

4. Potential future gene therapy for MoCD
   Experimental work is exploring gene therapy to deliver a working copy of the defective gene (such as MOCS1) to patient cells, aiming for long-term enzyme restoration. So far, this is at preclinical or very early clinical stages and not available as standard care. [56]

5. Stem-cell-based strategies (theoretical / research)
   In theory, stem-cell-derived liver or neural cells corrected for the gene defect could replace some enzyme activity. At present, however, there are no established stem-cell drugs or transplants that cure MoCD or sulfite oxidase deficiency, and such approaches remain experimental. [57]

6. Supportive nutrition and micronutrients for immune health
   Adequate protein, vitamins A, C, D, zinc, and iron support normal immune function. In children whose diet is limited by metabolic restrictions or feeding problems, careful nutritional planning is the safest way to “boost” immunity. [58]

Surgeries and procedures

1. Gastrostomy tube placement
   When oral feeding is unsafe or inadequate, a gastrostomy tube (G-tube) can be placed directly into the stomach. It allows reliable delivery of formula, water, and medicines, lowers aspiration risk, and makes daily care easier. The procedure is usually done endoscopically or surgically and carries the usual anesthesia risks. [59]

2. Anti-reflux surgery (fundoplication) in severe reflux
   If medical treatment fails and aspiration is frequent, surgeons may perform a fundoplication, wrapping the upper part of the stomach around the lower esophagus to reduce reflux. This is considered only after careful assessment because it is a major procedure in medically fragile children. [60]

3. Orthopedic surgery for contractures or scoliosis
   Over time, severe spasticity can lead to fixed joint contractures or spinal curvature. Selected children may benefit from tendon-lengthening or corrective spinal surgery to improve sitting, comfort, or care. Decisions are individualized and must balance benefit against the stress of surgery and recovery. [61]

4. Lens surgery for ectopia lentis
   If the lens is significantly dislocated and causing pain, high intra-ocular pressure, or unusable vision, eye surgeons may remove or reposition the lens and treat any associated glaucoma. This is mainly reported in isolated sulfite oxidase deficiency and some MoCD patients with lens problems. [62]

5. Tracheostomy in chronic respiratory failure (selected cases)
   In rare, very severe cases with chronic respiratory failure and repeated ICU stays, a tracheostomy may be considered to stabilize the airway and facilitate long-term ventilation and suctioning. This is an intensive, life-altering step and is considered within a broader palliative and ethical discussion. [63]

Prevention strategies

1. Carrier testing in parents and at-risk relatives – identifies carriers and informs reproductive planning. [64]

2. Prenatal or preimplantation genetic diagnosis – allows early detection of affected fetuses or selection of unaffected embryos where available. [65]

3. Avoiding consanguineous marriages where possible – may lower the chance of autosomal recessive diseases in high-risk populations. [66]

4. Early metabolic screening in future pregnancies with known risk – rapid testing and early fosdenopterin treatment in MoCD type A can improve outcomes. [67]

5. Prompt evaluation of neonatal seizures – any newborn with unexplained seizures should be urgently evaluated for metabolic causes, including MoCD. [68]

6. Standard vaccination and infection prevention – reduces complications that accelerate neurologic decline. [69]

7. Good nutritional care in infancy – prevents extra brain injury from hypoglycemia, severe under-nutrition, or significant vitamin deficiencies. [70]

8. Avoiding unnecessary nephrotoxic drugs where xanthine stones risk exists – protects kidneys already stressed by xanthine crystals. [71]

9. Regular follow-up at metabolic/neurology centers – allows early detection of complications and timely updates on new treatment options. [72]

10. Family education on seizure triggers and emergency plans – reduces delays in treatment during status epilepticus and can prevent severe hypoxic injury. [73]

When to see a doctor

Parents should seek urgent medical attention for any newborn or child who develops unexplained seizures, poor feeding, unusual stiffness or floppiness, or rapid loss of milestones, especially if there is a family history of early deaths or known MoCD/sulfite oxidase deficiency. [74]

Children with a confirmed diagnosis need regular planned visits to metabolic, neurology, nutrition, and palliative care teams. Any sudden change—new seizures, repeated vomiting, fever, breathing difficulty, reduced consciousness, or signs of pain—should prompt immediate medical review or emergency department evaluation, because infections and status epilepticus can progress very quickly in this condition. [75]

Diet: what to eat and what to avoid

In some patients, especially with sulfite oxidase and MoCD, specialists may trial a diet lower in methionine and sulfur-containing amino acids while ensuring enough total protein for growth. This usually means carefully designed formulas with controlled protein, plus allowed fruits, vegetables, and starches, planned by a metabolic dietitian. [76]

Families are usually advised to avoid high-protein, high-sulfur foods such as large amounts of meat, fish, eggs, and some high-sulfur protein supplements, unless specifically allowed in the plan. For patients with marked xanthine overproduction, low-purine diets (limiting organ meats, some fish, and certain legumes) and high fluid intake are recommended to reduce stone risk. All such restrictions are carefully balanced against the risk of malnutrition. [77]

Because each patient’s mutation, age, and clinical status are different, there is no single universal diet. The safest approach is regular review by a metabolic dietitian, with growth monitoring and blood tests to fine-tune both restrictions and supplements. [78]

Frequently asked questions

1. Is xanthine oxidase–sulfite oxidase deficiency the same as molybdenum cofactor deficiency?
   In most medical texts, yes: when both sulfite oxidase and xanthine oxidase are deficient, it is usually because the molybdenum cofactor is missing, which is called MoCD. [79]

2. How common is this disease?
   MoCD and isolated sulfite oxidase deficiency are extremely rare; only a few hundred patients are reported worldwide. Exact numbers are unknown because many infants may die before diagnosis is made. [80]

3. What are the earliest signs in babies?
   Typical early signs include poor feeding, intractable seizures starting in the first days of life, abnormal muscle tone, irritability, and rapidly progressive brain injury seen on MRI or CT. [81]

4. Can adults develop this condition?
   Most severe forms present in the neonatal period. There are rare late-onset or milder cases of MoCD, but they are exceptional. [82]

5. Is there a cure?
   For MoCD type A, early treatment with fosdenopterin can significantly improve survival and biochemical control but is not yet a complete cure. For other types and for isolated sulfite oxidase deficiency, there is no cure; treatment is supportive. [83]

6. Does diet alone cure the disease?
   No. Diet can modestly reduce the load of toxic sulfur or purine compounds and may provide some short-term clinical benefit in selected cases, but it does not fix the underlying enzyme or gene defect. [84]

7. What is the life expectancy?
   In classic early-onset MoCD without effective treatment, many infants die in early childhood due to severe neurologic damage and complications such as pneumonia. Early fosdenopterin in type A has improved survival, but long-term outcomes are still being studied. [85]

8. Can children with this condition learn and develop?
   Many early-onset patients have profound developmental disability; some late-onset or treated MoCD type A patients can achieve better milestones, but their abilities vary widely. Intensive supportive therapies aim to maximize each child’s comfort and skills. [86]

9. Are brothers and sisters at risk?
   Yes. Because the condition is usually autosomal recessive, each full sibling has a 25% chance of being affected, 50% chance of being a healthy carrier, and 25% chance of being unaffected and not a carrier. [87]

10. Can this condition be detected before birth?
    If the family mutation is known, prenatal testing or preimplantation genetic testing is possible in many countries. Families discuss options with a genetic counselor. [88]

11. Does fosdenopterin help all patients?
    It is specifically approved and designed for MoCD type A. It does not treat type B/C or isolated sulfite oxidase deficiency, because those conditions involve different points in the pathway. Genetic confirmation of the exact type is essential. [89]

12. Can parents do anything at home to stop seizures?
    Parents can follow a seizure action plan, use prescribed rescue medicines when indicated, protect the child from injury, and seek emergency help promptly. They should not change daily antiseizure medicine doses without medical advice. [90]

13. Is kidney disease always present?
    No. Kidney stones and kidney failure are more prominent in isolated xanthine oxidase deficiency (xanthinuria). In MoCD, neurologic problems dominate, though some biochemical features of xanthinuria may appear. [91]

14. What specialists should be involved in care?
    Care ideally involves a metabolic specialist, pediatric neurologist, dietitian, ophthalmologist, physiotherapist, occupational and speech therapists, palliative care, and social workers. [92]

15. Where can families find more information and support?
    Families can seek information from rare disease organizations, metabolic disease centers, and patient support groups that focus on MoCD and related metabolic disorders. These groups often share practical tips, updates on research, and emotional support networks. [93]

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.