Combined Oxidative Phosphorylation Deficiency Caused by Mutation in ELAC2

Combined oxidative phosphorylation deficiency caused by mutation in ELAC2 is a very rare genetic disease that mostly affects the heart and brain.[1] It belongs to a group of mitochondrial diseases in which several “energy factories” (oxidative phosphorylation complexes) inside the cell do not work properly at the same time. In this condition, a child is born with two faulty copies of the ELAC2 gene (one from each parent). This gene problem stops the mitochondria from making enough energy for the body.[2] The disease often starts in the first months or years of life and can cause a very thick heart muscle (hypertrophic cardiomyopathy), poor growth, weak muscles, high lactic acid in the blood, and sometimes early death.[2]

Combined oxidative phosphorylation deficiency-17 (COXPD17) is a very rare genetic mitochondrial disease caused by harmful changes (mutations) in a nuclear gene called ELAC2. In simple words, this gene helps finish and “cut” mitochondrial transfer RNAs (mt-tRNAs), which are tools that mitochondria use to make energy. When ELAC2 does not work properly, the mitochondrial energy factories cannot run the oxidative phosphorylation (OXPHOS) system correctly, so many organs—especially the heart, muscles and brain—do not get enough energy.

This disease usually appears in the first months or years of life. Babies often develop severe hypertrophic cardiomyopathy (very thick heart muscle), weak muscle tone (hypotonia), poor weight gain, feeding problems, and high lactic acid in the blood (lactic acidosis). Many children become very sick early in life and may die in infancy or early childhood, although some milder cases are now reported. There is no cure yet, and treatment focuses on careful supportive care and managing complications.

Because COXPD17 is autosomal recessive, the child usually receives one faulty ELAC2 gene from each parent. Parents are usually healthy carriers. Families often first learn about this condition after a baby becomes critically ill, or during genetic testing for unexplained cardiomyopathy and lactic acidosis. Genetic counseling is very important to help parents understand inheritance, recurrence risk in future pregnancies, and options such as prenatal or pre-implantation testing.

Other names

Doctors and scientists use several other names for this disease.[3] These names all describe the same basic problem: poor energy production in many parts of the mitochondrial respiratory chain because of changes in the ELAC2 gene.[3]

Common other names include:[3]

• Combined oxidative phosphorylation deficiency 17

• Combined oxidative phosphorylation defect type 17

• COXPD17

• ELAC2-related combined oxidative phosphorylation deficiency

• ELAC2-related mitochondrial cardiomyopathy

How ELAC2 and mitochondria work

The ELAC2 gene gives instructions to make an enzyme called zinc phosphodiesterase ELAC2.[4] This enzyme cuts the tail (3′ end) off immature transfer RNAs (tRNAs) inside mitochondria and also in the cell nucleus.[4] Cutting this tail is an important step to turn immature tRNA into mature tRNA, which is then used to build proteins.[4]

Mitochondria have their own DNA and make key proteins for the respiratory chain, which is the main energy system (oxidative phosphorylation).[5] If ELAC2 does not work well, mitochondrial tRNAs are not processed correctly, so many mitochondrial proteins cannot be made in normal amounts.[5] This leads to a combined deficiency of several respiratory chain complexes, and cells cannot make enough energy, especially in high-demand organs like the heart, brain, and muscles.[5]

Types

Because this disease is very rare, there is no official standard “type” list. However, based on published case reports and reviews, doctors see some repeating patterns.[6] These patterns can help them describe how the disease looks in different patients.[6]

• Infantile severe cardiac type
  In this pattern, disease starts in the first months of life with very thick heart muscle, heart failure, high lactic acid, weak muscles, feeding problems, and often early death.[7] Brain problems such as seizures or breathing pauses can also appear.[7]

• Infantile cardio-neuro type
  Here, the baby has heart disease plus strong nervous system problems like seizures, poor muscle tone, and delayed development.[8] The heart and brain are both badly affected from early infancy.[8]

• Childhood mixed multi-organ type
  Some children live longer and show a mix of heart disease, developmental delay, muscle weakness, hearing problems, and growth failure.[9] The severity can vary a lot between children, even with similar ELAC2 mutations.[9]

• Milder or later-onset neurological type
  Rarely, ELAC2 changes present later with mainly neurological signs such as movement problems, behavior changes, and learning difficulties, with less severe heart problems.[10] This seems to happen with some milder ELAC2 variants.[10]

Causes

For this disease, the main true cause is having two faulty copies of ELAC2 (autosomal recessive inheritance).[11] Other “causes” listed below are different kinds of mutations or things that can trigger or worsen symptoms. They do not change the basic fact that the root problem is genetic.[11]

1. Homozygous ELAC2 mutation
   The child inherits the same disease-causing ELAC2 variant from both parents. This completely breaks or strongly reduces ELAC2 function in mitochondria, causing combined oxidative phosphorylation deficiency.[12]

2. Compound heterozygous ELAC2 mutations
   The child inherits two different damaging ELAC2 variants (one from each parent). Together, these variants strongly weaken ELAC2 activity and lead to the same disease.[13]

3. Missense mutations in the catalytic site
   A single amino acid change in the active site of ELAC2 can lower its cutting ability on tRNA tails. This reduces proper tRNA processing and harms mitochondrial protein production.[14]

4. Truncating (nonsense or frameshift) mutations
   These mutations create a shorter, often unstable ELAC2 protein that cannot work well. The loss of this enzyme sharply cuts mitochondrial tRNA processing.[15]

5. Mutations affecting mitochondrial targeting sequence
   Some variants may disturb the signal that sends ELAC2 to mitochondria. If less ELAC2 reaches mitochondria, tRNA processing there fails, and energy production falls.[16]

6. Mutations disturbing binding to partner proteins
   ELAC2 works together with other proteins (such as TRMT10C and SDR5C1) for certain mitochondrial tRNAs.[17] Changes that weaken these interactions can impair tRNA processing.[17]

7. Variants that reduce enzyme stability
   Some ELAC2 mutations make the protein fold poorly or break down faster. Even if the enzyme can work, there is not enough of it, leading to partial deficiency.[18]

8. Mutations mainly affecting nuclear tRNA processing
   ELAC2 also processes nuclear tRNAs. Variants that disturb this function can add extra stress to cells, especially neurons, and may shape the neurological features.[19]

9. Mutations mainly affecting mitochondrial tRNA processing
   Other variants mainly impair mitochondrial tRNA cutting. This directly harms mitochondrial protein synthesis and respiratory chain function in the heart and brain.[20]

10. Consanguinity (parents related by blood)
    When parents are related (for example, cousins), they are more likely to carry the same rare ELAC2 mutation. This increases the chance that a child gets two faulty copies.[21]

11. Other mitochondrial DNA changes in the same person
    Some patients may also have small changes in mitochondrial DNA that, together with ELAC2 mutations, worsen energy failure. This “double hit” can make the disease more severe.[22]

12. Intercurrent infections
    Fever and infections sharply increase energy needs. In a child with ELAC2-related OXPHOS deficiency, this can cause sudden worsening of heart or brain symptoms.[23]

13. Fasting or poor food intake
    Not eating for long periods forces the body to use fat and protein for energy, which needs healthy mitochondria. In this disease, fasting can increase lactic acid and trigger crisis.[24]

14. Certain mitochondrial-toxic drugs
    Some medicines (for example, valproic acid and some antibiotics) can stress mitochondria. In a child with ELAC2 mutations, they may make symptoms worse, so doctors use them very carefully.[25]

15. Strong physical stress or surgery
    Big operations or heavy illness increase the body’s energy demand. This can unmask or aggravate heart failure and lactic acidosis in a child with this condition.[26]

16. Low oxygen states (hypoxia)
    Low oxygen levels reduce the efficiency of oxidative phosphorylation. In a child whose mitochondria already work poorly, hypoxia can quickly lead to organ failure.[27]

17. Metabolic stress from seizures
    Seizures greatly increase energy use in the brain. Repeated seizures in ELAC2-related disease can worsen brain injury and lactic acidosis.[28]

18. Failure to treat heart failure early
    If heart failure is not recognized and treated, the already weak heart may deteriorate faster, leading to shock or sudden death.[29]

19. No access to early genetic diagnosis
    Without timely genetic testing, supportive care and family planning may be delayed. This does not cause the disease, but it can worsen outcomes for the child and family.[30]

20. Parents both carrying ELAC2 variants (carrier state)
    The underlying background reason is that both parents are healthy carriers of an ELAC2 mutation. Each pregnancy has a 25% chance that the child will be affected.[31]

Symptoms

Not every child has the same signs, but many reports show a group of common symptoms.[32] The heart and brain are usually the most affected organs.[32]

1. Hypertrophic cardiomyopathy (very thick heart muscle)
   The walls of the heart become thick and stiff, so the heart cannot pump or relax normally. Babies may breathe fast, sweat with feeds, and become tired easily.[33]

2. Heart failure symptoms
   There may be poor feeding, swelling, trouble breathing, enlarged liver, and poor weight gain because the heart cannot send enough blood to the body.[34]

3. Low muscle tone (hypotonia)
   The baby may feel “floppy” when lifted, have poor head control, and move less than expected. This happens because muscles do not get enough energy.[35]

4. Global developmental delay
   Sitting, crawling, walking, and talking may be much slower than in other children. Energy shortage in the brain and muscles slows learning and movement.[36]

5. Seizures
   Some babies develop fits or seizures, which may be hard to control. These reflect serious brain involvement from mitochondrial energy failure.[37]

6. Episodes of central apnea or breathing pauses
   The child may suddenly stop breathing for short times, especially during sleep. This suggests brainstem involvement and can be life-threatening.[38]

7. Lactic acidosis
   High lactic acid in blood or cerebrospinal fluid is common. It causes fast breathing, vomiting, and tiredness and is a key sign of mitochondrial disease.[39]

8. Failure to thrive and poor growth
   Despite feeding, babies may not gain weight or grow as expected. This happens because energy production is inefficient, and heart or feeding problems may limit intake.[40]

9. Encephalopathy (brain dysfunction)
   Children may show altered alertness, poor responsiveness, and abnormal movements. This reflects widespread brain injury from chronic low energy.[41]

10. Microcephaly (small head size)
    Some children have a smaller than normal head, showing poor brain growth over time.[42]

11. Muscle weakness and fatigue
    Children may tire with small efforts and have difficulty holding up the head or moving limbs against gravity.[43]

12. Hearing loss
    A few patients have sensorineural hearing loss, meaning damage to the inner ear or nerve. This is seen in several mitochondrial diseases, including some ELAC2 cases.[44]

13. Intellectual disability or learning difficulties
    When children survive longer, they may show learning and behavior problems because of chronic brain energy shortage.[45]

14. Feeding problems and vomiting
    Many infants have trouble sucking, swallowing, or keeping food down, partly from weak muscles and partly from heart and metabolic stress.[46]

15. Early death in severe forms
    In the most severe infantile cases, the combination of heart failure, lactic acidosis, and brain involvement can lead to death in early infancy or early childhood.[47]

Diagnostic tests

Because this disease is very rare and complex, doctors use many tests together. No single test is enough. They combine clinical examination, blood tests, heart and brain tests, and finally genetic testing for ELAC2.[48]

Physical exam tests

1. General pediatric physical exam
   The doctor checks weight, length, head size, vital signs, breathing, and overall look of the child. Poor growth, small head, weak cry, or abnormal breathing can suggest a serious metabolic or heart problem.[49]

2. Cardiovascular exam
   The doctor listens to the heart, checks heart rate, rhythm, heart sounds, murmurs, liver size, and swelling of legs or tummy. Fast heart rate, gallop rhythm, enlarged liver, and poor pulses suggest cardiomyopathy and heart failure.[50]

3. Neurological exam
   The doctor looks at alertness, muscle tone, strength, reflexes, eye movements, and coordination. Floppy tone, poor reflexes, abnormal eye movements, or seizures point to brain and nerve involvement.[51]

4. Respiratory exam
   Breathing rate, effort, chest movement, and oxygen levels are checked. Fast breathing, chest retractions, or low oxygen can reflect heart failure, lactic acidosis, or central apnea.[52]

Manual (bedside) tests

5. Manual muscle testing (MRC scale)
   The clinician gently tests how strongly the child can move arms and legs against resistance. Low scores show muscle weakness, which fits with mitochondrial myopathy in this condition.[53]

6. Observation of developmental milestones
   Simple checks like “Can the baby hold the head?”, “Can the child sit or walk?” act like a manual test of function. Significant delay suggests a global developmental problem related to brain and muscle energy failure.[54]

7. Bedside feeding and swallowing assessment
   The team watches the baby feed, looking for poor sucking, choking, or fatigue with feeding. These signs point to neuromuscular weakness and heart failure.[55]

8. Bedside heart failure scoring (clinical scales)
   Some centers use simple scoring systems based on breathing, feeding, and liver size to rate heart failure. A high score suggests significant cardiomyopathy and guides urgent testing.[56]

Lab and pathological tests

9. Serum lactate and pyruvate
   High lactate (often with high lactate-to-pyruvate ratio) is a common sign of mitochondrial dysfunction. In ELAC2-related disease, persistently high lactate supports a diagnosis of oxidative phosphorylation defect.[57]

10. Blood gas analysis
    This test measures pH, carbon dioxide, oxygen, and bicarbonate. It helps detect metabolic acidosis from lactic acid build-up and shows how well the child is breathing and perfusing.[58]

11. Muscle enzymes and liver enzymes
    Blood tests like creatine kinase (CK), AST, and ALT may be raised, showing muscle or liver stress. These findings are nonspecific but fit with systemic mitochondrial disease.[59]

12. Plasma amino acids, acylcarnitine profile, and urine organic acids
    These metabolic screens help rule out other inherited metabolic disorders and sometimes show patterns that support mitochondrial dysfunction.[60]

13. Respiratory chain enzyme analysis in muscle or fibroblasts
    A biopsy sample (muscle or skin fibroblasts) can be tested for activity of complexes I–IV or I–V. In this disease, a combined deficiency of several complexes is usually found.[61]

14. Genetic testing for ELAC2 (single gene, panel, or exome)
    DNA from blood is analyzed to find pathogenic variants in ELAC2. Modern gene panels and whole-exome sequencing have identified many of the reported cases and are now the gold standard for confirming the diagnosis.[62]

Electrodiagnostic tests

15. Electrocardiogram (ECG)
    ECG records the electrical activity of the heart. It can show fast heart rates, conduction problems, and patterns that fit with hypertrophic cardiomyopathy or heart failure.[63]

16. Electroencephalogram (EEG)
    EEG records brain electrical activity. It can show abnormal discharges or seizure patterns in children with fits, encephalopathy, or central apnea.[64]

17. Electromyography (EMG) and nerve conduction studies (NCS)
    These tests look at muscle and nerve function. They can help show whether weakness is mainly from muscle disease, nerve disease, or both, which is useful in mitochondrial conditions.[65]

Imaging tests

18. Echocardiography (heart ultrasound)
    This is a key test in ELAC2-related disease. It shows the thickness of heart walls, pumping function, valve status, and any outflow tract obstruction. It helps confirm hypertrophic cardiomyopathy and monitor its progression.[66]

19. Cardiac MRI
    Cardiac MRI gives very detailed pictures of the heart muscle and can show the extent and pattern of thickening and scarring. It helps in complex cases and in research on ELAC2-related cardiomyopathy.[67]

20. Brain MRI
    Brain MRI can show atrophy (loss of brain volume), white-matter changes, or other lesions linked to mitochondrial encephalopathy. These findings, together with clinical signs and genetic results, support the diagnosis.[68]

Non-Pharmacological Treatments (Therapies and Other Supports)

All of these must be planned and supervised by a specialist mitochondrial / cardiology team. They do not replace medicines when these are needed.

1. Multidisciplinary specialist care
Children with COXPD17 need a team including cardiologists, neurologists, metabolic and genetic specialists, dietitians, physiotherapists and palliative care experts. Regular joint clinics allow early detection of heart failure, seizures, nutritional problems and developmental delay. Coordinated care improves quality of life and helps families understand complex decisions such as intensive care or advanced therapies.

2. Individualized nutrition and high-calorie feeding
Energy shortage is a central problem, so providing enough calories and protein is essential. Dietitians familiar with mitochondrial disease design feeding plans with frequent meals, sometimes high-energy formulas or night feeds, to prevent fasting and catabolism. If oral intake is poor, tube feeding (nasogastric or gastrostomy) may be used to maintain weight and reduce hospital admissions.

3. Avoidance of prolonged fasting and metabolic stress
Children with mitochondrial disease often decompensate during illness, surgery or long periods without food. Families are taught “sick-day” plans: give extra fluids and carbohydrates, avoid long fasting, and seek early medical help. Hospitals should provide IV glucose during procedures and carefully monitor fluids and lactate.

4. Physiotherapy and gentle exercise
Regular, low-to-moderate intensity physical therapy helps maintain muscle strength, joint mobility and respiratory capacity without over-exertion. Therapists adapt exercise intensity to the child’s tolerance and heart status. Short, frequent sessions are safer and more effective than sudden intense activity.

5. Occupational therapy and assistive devices
Occupational therapists support everyday activities like sitting, feeding, playing and eventually school work. They may recommend adapted seating, splints, wheelchairs or communication devices to reduce energy cost and prevent contractures. This helps children participate in family and social life as fully as possible.

6. Speech, feeding and swallowing therapy
Feeding specialists assess swallowing safety and risk of aspiration. They may teach special positions, thickened fluids or pacing during feeds. Early intervention can reduce chest infections, improve nutrition, and support early language and communication skills.

7. Respiratory support and airway clearance
Some children develop weak breathing muscles or recurrent chest infections. Chest physiotherapy, suctioning, cough-assist devices, and sometimes non-invasive ventilation (like BiPAP) during sleep improve oxygen levels and reduce hospitalisations. Decisions about invasive ventilation or tracheostomy require careful discussion with the family.

8. Cardiac monitoring and activity adjustment
Regular echocardiograms, ECGs and Holter monitoring detect worsening hypertrophic cardiomyopathy or arrhythmias. Doctors then adjust medicines and advise on safe activity levels. In some cases, competitive sports or very strenuous exercise are restricted because of sudden-death risk in hypertrophic cardiomyopathy.

9. Strict infection prevention
Even minor infections can trigger severe decompensation. Families are encouraged to follow routine vaccines, including influenza and pneumococcal, and to practise good hand hygiene. Early medical assessment and sometimes early antibiotics or antivirals are important when a child with mitochondrial disease becomes unwell.

10. Emergency “care plan” and hospital letter
A written emergency plan explains the child’s diagnosis, common complications, dangerous medications to avoid, and recommended fluids and monitoring. Parents can present this document when they arrive at emergency departments so staff act quickly and consistently.

11. Genetic counselling and family planning support
Specialists explain autosomal recessive inheritance, carrier status and recurrence risk. Families can discuss options such as prenatal diagnosis or pre-implantation genetic testing in future pregnancies, and screening of at-risk relatives. This information can be emotionally heavy, so counselling needs to be gentle and ongoing.

12. Developmental and early-intervention programs
Because many children have motor or learning delays, early referral to developmental services is recommended. Structured stimulation, play therapy and tailored schooling support can improve skills and independence, even when medical problems remain serious.

13. Psychological and social support for families
Caring for a child with severe mitochondrial disease is physically and emotionally exhausting. Counsellors, psychologists and social workers help families cope with stress, grief, financial strain and difficult decisions about intensive care or palliation. Support groups and patient organisations can reduce isolation.

14. Palliative care and symptom control
Palliative care does not mean “giving up”; it focuses on comfort, symptom relief and quality of life. Teams manage pain, breathlessness, feeding discomfort, and anxiety, while respecting family values about hospital care, home care, and end-of-life wishes.

15. Careful anaesthesia and surgery planning
Children with mitochondrial disease are at higher risk during anaesthesia. Anaesthetists must avoid long fasting, prevent low blood sugar, monitor temperature and acid–base balance, and avoid drugs known to worsen mitochondrial function where possible. Pre-operative planning with the metabolic team is essential.

16. Avoidance of mitochondrial-toxic medicines where possible
Certain drugs, such as valproic acid, some aminoglycosides, linezolid and high-dose propofol, may worsen mitochondrial function in susceptible patients. Doctors aim to use safer alternatives if available, especially in infants with known mitochondrial disease.

17. Temperature and metabolic stress control during illness
High fever, severe dehydration or low blood sugar can all push cells into deeper energy crisis. In hospital, staff actively treat fever, give IV fluids with glucose, and correct acidosis, while continuously monitoring the heart and breathing.

18. Structured school and educational accommodations
For older children who survive beyond infancy, fatigue and heart problems may limit attendance. Schools can offer shorter days, rest breaks, home-based learning, and emergency plans. These accommodations protect health and support social development.

19. Regular vision and hearing monitoring
Some mitochondrial diseases affect eyes and ears. Regular screening ensures that problems such as hearing loss or visual impairment are detected early and treated with aids, improving communication and learning.

20. Long-term follow-up in a mitochondrial centre
Because knowledge is rapidly evolving, follow-up in a specialised mitochondrial centre allows access to clinical trials, new supplements or therapies, and updated care standards. These centres also collect data that may guide future treatments for ELAC2-related disease.

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Drug Treatments

Important safety note: these drugs do not cure ELAC2-related COXPD17. They are used to control symptoms such as heart failure, seizures or metabolic imbalance. Doses are highly individual, especially in infants, and must be set by specialists. Many uses are off-label but based on general heart-failure or mitochondrial-disease practice.

1. Levocarnitine (CARNITOR – metabolic support)
Levocarnitine is an FDA-approved drug for carnitine deficiency. It helps move long-chain fatty acids into mitochondria and removes toxic acyl groups by forming acylcarnitines that can be excreted. In mitochondrial disease, clinicians sometimes use oral or IV levocarnitine (for example, 50–100 mg/kg/day in divided doses) to support energy metabolism and treat secondary carnitine deficiency. Main side effects include nausea, diarrhoea and fishy body odour.

2. Coenzyme Q10 (ubiquinone – antioxidant / electron carrier)
Coenzyme Q10 is a key part of the electron transport chain and is widely used in mitochondrial “cocktails”. While many preparations are marketed as supplements, some pharmaceutical-grade products are described in regulatory documents. Typical mitochondrial doses are much higher than standard dietary use (for example, 5–30 mg/kg/day), divided with meals. Side effects are usually mild (GI upset, headache). Evidence suggests possible improvement in exercise tolerance and fatigue in some mitochondrial disorders.

3. Riboflavin (vitamin B2 – mitochondrial cofactor)
High-dose riboflavin is often used as part of a mitochondrial cocktail because it acts as a precursor for FAD and FMN, which are essential for complex I and II function. Doses in mitochondrial disease can be 10–50 mg/kg/day (up to a practical maximum), divided with food. It is generally safe; urine may turn bright yellow. Evidence from case series suggests benefit in some complex I deficiencies and related conditions.

4. Thiamine (vitamin B1 – cofactor for pyruvate dehydrogenase)
Thiamine helps the pyruvate dehydrogenase complex convert pyruvate to acetyl-CoA, connecting glycolysis to the TCA cycle. High doses (often 10–40 mg/kg/day up to a max dose) are used in some mitochondrial and metabolic disorders to reduce lactic acidosis and improve energy metabolism. Side effects are rare and usually mild allergic reactions. In severely ill children, IV thiamine may be given as part of acute management.

5. Alpha-lipoic acid (antioxidant)
Alpha-lipoic acid is an antioxidant and cofactor in mitochondrial enzyme complexes. It is sometimes used at doses such as 10–20 mg/kg/day to reduce oxidative stress and support mitochondrial function. Evidence is mostly from small studies and expert opinion. Side effects can include nausea, skin rash and rarely low blood sugar.

6. L-arginine (nitric-oxide–related amino acid)
L-arginine is used more often in mitochondrial stroke-like episodes (such as MELAS), but some clinicians include it in broader mitochondrial support to improve blood flow and endothelial function. Doses vary widely (for example, 150–300 mg/kg/day orally in divided doses in some protocols). Side effects may include GI upset and low blood pressure at high IV doses.

7. Beta-blockers (e.g., propranolol) for hypertrophic cardiomyopathy
Beta-blockers reduce heart rate and myocardial oxygen demand, allowing the thick heart muscle to relax better. Propranolol and other beta-blockers are commonly used in paediatric hypertrophic cardiomyopathy, with dose carefully titrated based on weight and response. Common side effects include low heart rate, low blood pressure, tiredness and sometimes bronchospasm.

8. ACE inhibitors (e.g., enalapril) for heart failure
ACE inhibitors help relax blood vessels, reduce afterload and prevent harmful heart remodelling. In children with cardiomyopathy and reduced function, enalapril or similar drugs may improve symptoms and long-term outcomes when used as part of guideline-directed heart-failure therapy. Side effects include cough, low blood pressure, kidney dysfunction and high potassium.

9. Diuretics (e.g., furosemide) for fluid overload
When heart failure leads to fluid retention and lung congestion, loop diuretics such as furosemide help remove excess fluid through the kidneys. Paediatric doses are weight-based, and close monitoring of electrolytes and kidney function is essential. Side effects include dehydration, low blood pressure, low potassium and hearing problems at very high IV doses.

10. Mineralocorticoid receptor antagonists (e.g., spironolactone)
Spironolactone blocks aldosterone, reducing sodium and water retention and helping protect the heart from remodelling. It is often added to ACE inhibitors and diuretics in chronic heart failure. Side effects include high potassium, breast enlargement and menstrual irregularities in older patients.

11. SGLT2 inhibitors (emerging in older patients)
In older adolescents and adults with heart failure, sodium–glucose co-transporter-2 (SGLT2) inhibitors are now part of standard therapy for heart failure with reduced ejection fraction, regardless of diabetes. Their direct role in paediatric mitochondrial cardiomyopathy is still unclear and highly specialist. Side effects include genital infections and volume depletion.

12. Levetiracetam for seizure control
If seizures occur, levetiracetam is often preferred because it has limited mitochondrial toxicity compared with some older antiseizure drugs. The FDA label describes typical adult starting doses of 1000 mg/day in divided doses, adjusted for age and kidney function; paediatric dosing is weight-based. Common side effects are sleepiness, irritability and behavioural changes.

13. Other antiseizure medicines (e.g., lamotrigine, clobazam)
Depending on seizure type and response, other antiseizure medicines may be used. Doctors try to avoid drugs such as valproic acid that can worsen mitochondrial function. Each medicine has its own dosing schedule and side-effect profile, and careful neurologist supervision is essential.

14. Sodium bicarbonate and other buffering agents
In severe lactic acidosis, IV sodium bicarbonate or other buffers may be used in intensive care to correct blood pH and reduce strain on the heart and brain. This is a temporary supportive measure and must be closely monitored to avoid sodium overload or paradoxical effects.

15. Anti-arrhythmic drugs (e.g., amiodarone)
If dangerous heart rhythm abnormalities occur, anti-arrhythmic drugs like amiodarone may be used. These drugs can be life-saving but have important side effects, including thyroid, lung and liver toxicity, so they require expert cardiology care and regular monitoring.

16. Inotropes (e.g., milrinone, dobutamine) in intensive care
During acute decompensated heart failure, IV inotropes may be needed to support heart pumping while other treatments are optimised. These drugs are short-term and used only in monitored units, because they can cause arrhythmias and low blood pressure.

17. Proton pump inhibitors or H2 blockers (for GI protection)
Children taking multiple medicines, especially in intensive care, may receive acid-suppressing drugs to prevent stress ulcers and reflux. These do not treat the underlying mitochondrial disease but can reduce pain, vomiting and bleeding risk. Long-term use must be balanced against risks such as infections.

18. Antiemetics and prokinetic drugs
For severe nausea, vomiting or slow stomach emptying, antiemetic or prokinetic drugs can help maintain nutrition and comfort. Choices must consider possible heart or neurologic side effects.

19. Vitamin D and calcium (bone and muscle health)
Because limited mobility, chronic illness and some medicines affect bone density, vitamin D and calcium supplementation may be recommended following standard paediatric guidelines. Adequate levels support muscle and bone health but do not directly correct the ELAC2 defect.

20. Routine vaccines and, when indicated, specific prophylactic drugs
Vaccines are part of standard paediatric care and reduce infection-triggered decompensation. In some very fragile patients, doctors may also consider specific prophylactic antibiotics or antivirals during outbreaks, but this is highly individualised.

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Dietary Molecular Supplements

Doses are only typical ranges discussed in mitochondrial practice literature. Actual dosing must be set by a specialist.

1. Coenzyme Q10 – discussed above; central antioxidant and electron carrier; often 5–30 mg/kg/day with food.

2. Riboflavin (B2) – cofactor for complex I/II; often 10–50 mg/kg/day; supports electron transport.

3. Thiamine (B1) – helps pyruvate dehydrogenase; widely used for lactic acidosis and energy metabolism.

4. Niacinamide (B3) – precursor of NAD+/NADH, potentially supporting redox balance; doses vary.

5. L-carnitine – described above; supports fatty-acid transport and removal of toxic acyl groups.

6. Alpha-lipoic acid – antioxidant and cofactor; may reduce oxidative stress in mitochondria.

7. Creatine monohydrate – energy buffer in muscle cells; sometimes used to support muscle strength and endurance.

8. Arginine / citrulline – nitric-oxide–related amino acids; more evidence in MELAS, but sometimes used more broadly.

9. Vitamins C and E (paired antioxidants) – used together as a redox couple to avoid pro-oxidant effects when given alone.

10. Folinic acid or other B-complex vitamins – support one-carbon metabolism and DNA repair; sometimes included in broader mitochondrial cocktails.

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Immunity-Boosting / Regenerative / Stem-Cell–Related Drugs

There are no standard stem-cell or regenerative drugs proven to treat ELAC2-related COXPD17 directly. A few approaches may be discussed in highly specialised centres or research settings:

1. Intravenous immunoglobulin (IVIG) – sometimes used in mitochondrial patients with co-existing immune disorders or recurrent infections; it provides pooled antibodies but does not fix the genetic defect.

2. Granulocyte colony-stimulating factor (G-CSF) – used only if there is significant neutropenia from other causes; stimulates white-cell production to reduce infection risk.

3. Hematopoietic stem-cell transplantation (HSCT) – only considered in very specific mitochondrial disorders with bone-marrow failure; there is no routine indication for ELAC2-related COXPD17, and the risks are high.

4. Experimental gene-therapy or gene-editing approaches – research in nuclear-encoded mitochondrial diseases is evolving, but there is no approved gene therapy for ELAC2 at present. Any such treatment would be available only in clinical trials.

5. Mitochondria-targeted antioxidants (e.g., idebenone, newer agents) – some agents are being studied in mitochondrial disorders to protect cells from oxidative damage. Their role in COXPD17 remains experimental.

6. Participation in clinical trials of novel metabolic or genetic therapies – when available, clinical trials may test drugs that boost mitochondrial biogenesis or correct specific pathways. Families interested in such trials should discuss risks and benefits with their care team.

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Surgical and Procedural Treatments

1. Gastrostomy tube placement – for children who cannot feed safely or adequately by mouth, a PEG or surgical gastrostomy provides long-term access for feeds and medicines, improving nutrition and reducing aspiration.

2. Implantable cardioverter-defibrillator (ICD) or pacemaker – in selected older children with serious arrhythmias or high risk of sudden death, device therapy may be considered, though data in COXPD17 are limited.

3. Heart transplantation – in extremely selected cases with end-stage cardiomyopathy but relatively preserved other organs, heart transplant may be discussed; however, systemic mitochondrial disease often limits suitability.

4. Tracheostomy and long-term ventilation – if chronic respiratory failure develops, tracheostomy and home ventilation can sometimes stabilise breathing, but the decision is complex and depends on family goals and child comfort.

5. Orthopaedic or spinal surgery – for children who live longer and develop contractures or scoliosis, corrective surgery may improve comfort and seating, but anaesthetic risk must be carefully assessed in mitochondrial disease.

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Prevention and Risk Reduction

Although you cannot “prevent” ELAC2 mutations, you can reduce complications:

1. Early diagnosis and regular specialist follow-up.

2. Consistent infection prevention and vaccination.

3. Avoidance of fasting and quick response to illness.

4. Careful choice of medicines, avoiding mitochondrial-toxic drugs when possible.

5. Written emergency plan for hospitals and emergency services.

6. Good nutrition and hydration every day.

7. Regular heart monitoring to detect early deterioration.

8. Regular developmental, hearing and vision checks.

9. Genetic counselling for family planning.

10. Seeking psychosocial support to avoid caregiver burnout.

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When to See a Doctor or Go to Emergency

Parents or caregivers should seek urgent medical attention if a child with ELAC2-related disease shows any of these:

• Fast or difficult breathing, blue lips or fingers, or very fast heart rate.

• Sudden worsening tiredness, poor feeding, vomiting or unable to keep fluids down.

• New seizures, changes in consciousness, unusual sleepiness or confusion.

• Swelling of legs, tummy, or eyelids, or rapid weight gain from fluid.

• High fever, suspected infection, or exposure to serious viral illnesses.

Regular planned visits to the mitochondrial or cardiology clinic are also important, even if the child seems stable, because subtle changes can be picked up early and treatment adjusted.

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Diet: What to Eat and What to Avoid

1. Eat regular, frequent meals
Small, frequent meals with balanced carbohydrates, protein and fat help prevent long gaps without energy, which can trigger decompensation in mitochondrial disease.

2. Focus on nutrient-dense foods
Offer foods rich in protein (lean meat, eggs, dairy, legumes), healthy fats (olive oil, nuts, seeds) and complex carbohydrates (whole grains, fruits, vegetables) to support growth and energy.

3. Ensure enough fluids
Proper hydration helps circulation and kidney function, especially when diuretics are used. During illness, oral rehydration solutions may be recommended.

4. Consider specialised formulas when needed
High-calorie or semi-elemental formulas can reduce the work of digestion and improve nutrient absorption in children who struggle with standard feeds.

5. Avoid prolonged fasting and crash dieting
Skipping meals or restrictive diets are dangerous in mitochondrial disease, because they push the body into breaking down its own tissues for energy, raising lactic acid.

6. Avoid excess alcohol and smoking exposure in the household
For older adolescents and adults, alcohol and smoking can worsen oxidative stress and heart health. For children, second-hand smoke should be avoided.

7. Use supplements only under specialist advice
“Natural” supplements are not always safe; doses in mitochondrial disease are often higher than usual. Always check with the mitochondrial team before starting or stopping any supplements.

8. Avoid unnecessary iron unless deficient
Some guidance suggests avoiding iron supplements unless there is proven deficiency, because iron can worsen oxidative stress. This must be balanced against the risk of anaemia.

9. Limit sugary drinks but do not restrict carbohydrates when sick
In daily life, very sugary drinks should be limited for dental and metabolic health, but during illness, glucose-containing fluids or IV glucose may be lifesaving; this balance is set by the care team.

10. Plan meals in advance to reduce stress
Batch-cooking, easy-to-reheat meals and online shopping can protect caregivers’ energy and make it easier to keep up with frequent small meals.

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Frequently Asked Questions

1. Is combined oxidative phosphorylation deficiency-17 (COXPD17) the same as all mitochondrial diseases?
No. COXPD17 is one specific mitochondrial disease caused by ELAC2 mutations and usually presents with severe hypertrophic cardiomyopathy in early life. Many other mitochondrial diseases involve different genes and organs.

2. Can COXPD17 be cured?
At present, there is no cure or gene therapy approved for COXPD17. Treatment focuses on heart-failure management, seizure control, nutritional support and prevention of complications. Research on mitochondrial and genetic therapies is ongoing.

3. Why is the heart so strongly affected?
Heart muscle needs constant high energy. When oxidative phosphorylation is impaired, the heart cannot meet its energy demands, so muscle fibres thicken and heart function gradually fails, leading to hypertrophic cardiomyopathy and heart failure.

4. Are all ELAC2 mutations equally severe?
No. Different mutations can produce different levels of enzyme function. Newer studies show that some people with ELAC2 variants have milder or more variable disease, but many reported cases are still very severe in infancy.

5. How is the diagnosis confirmed?
Doctors combine clinical findings, blood tests (including lactate), heart imaging, sometimes muscle biopsy and, most importantly, genetic testing that identifies pathogenic variants in both copies of ELAC2. Respiratory chain enzyme studies may show reduced activity of multiple complexes.

6. Is this condition always fatal in early childhood?
Many reported cases have had poor outcomes, but increasing awareness and better supportive care mean some children may live longer. However, COXPD17 remains a serious, life-limiting condition that requires honest discussions about prognosis and goals of care.

7. Can siblings or future children be tested?
Yes. Once the ELAC2 variants are known in a family, carrier testing and prenatal or pre-implantation genetic testing can be discussed with a genetics team.

8. Are “mitochondrial cocktails” proven to work?
Many clinicians use mitochondrial cocktails of vitamins and cofactors because they are usually low-risk and there is some evidence of benefit in certain mitochondrial disorders. However, high-quality trials are limited, and responses vary between individuals.

9. Which medicines are dangerous in mitochondrial disease?
Examples include valproic acid in some mitochondrial conditions, certain aminoglycosides, linezolid and prolonged high-dose propofol. Doctors weigh risks and benefits and choose safer alternatives when possible.

10. Can children with COXPD17 go to school or nursery?
Some children can attend with adaptations such as shortened days, rest breaks and emergency plans. Others may be too medically fragile and need home-based education. Decisions are individual and change over time.

11. Does exercise help or harm?
Gentle, supervised activity can help maintain strength and function, but over-exertion can be risky, especially with cardiomyopathy. Physiotherapy and cardiology teams guide safe levels of activity.

12. Are there special anaesthetic precautions?
Yes. Anaesthetists must avoid long fasting, maintain blood sugar, manage temperature and choose drugs carefully. Surgery should be planned in centres experienced with mitochondrial disease whenever possible.

13. What emotional support is available for families?
Psychologists, social workers, spiritual care teams and mitochondrial patient organisations can provide counselling, practical help and connection with other families facing similar conditions.

14. Should families consider clinical trials?
Clinical trials may offer access to experimental therapies, but they can also involve burdensome procedures and unknown risks. Families should discuss all options carefully with their specialist team before enrolling.

15. Is online information reliable?
Quality varies widely. It is safer to rely on information from recognised mitochondrial centres, national patient organisations, and peer-reviewed medical sources, and to check any treatment ideas with your child’s specialist team.

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 19, 2025.