Cardiomyopathy-Hypotonia-Lactic Acidosis Syndrome

Cardiomyopathy-hypotonia-lactic acidosis syndrome (CHLAS) is a very rare mitochondrial disease pattern. Babies are often sick soon after birth or in early infancy. The heart muscle is thick or weak (cardiomyopathy). Muscle tone is low (hypotonia). Blood lactate is high (lactic acidosis) because the mitochondria cannot make enough energy. Some children have severe disease and die early; others live longer with careful care. CHLAS overlaps with named genetic entities such as SLC25A3-related mitochondrial phosphate carrier deficiency and AGK-related Sengers syndrome—both present with cardiomyopathy, hypotonia and lactic acidosis. BioMed Central+4Orpha+4MalaCards+4

Cardiomyopathy-hypotonia-lactic acidosis syndrome is a group of rare, mostly genetic disorders in babies and young children where three problems happen together:

• Cardiomyopathy: the heart muscle becomes thick or weak, and the heart cannot pump blood well.

• Hypotonia: the muscles are “floppy” or weak, so the baby feels soft when lifted and has trouble holding up the head or feeding.

• Lactic acidosis: the body makes too much lactic acid because cells cannot make energy efficiently, so acid builds up in the blood and tissues.

The root problem is usually mitochondrial energy failure—the tiny “power plants” inside cells cannot produce enough ATP. In several well-described forms (for example, fatal infantile cardioencephalomyopathy due to cytochrome-c oxidase (COX) deficiency), babies develop severe lactic acidosis, low muscle tone, and a hypertrophic or dilated cardiomyopathy very early in life. Orpha+1

Doctors diagnose CHLAS by piecing together the story: heart findings by echocardiogram or MRI, very high lactate in blood or CSF, muscle weakness on exam, and genetic testing that finds a causative variant. Multiple genes can be involved (for example SLC25A3 and AGK), so genetic testing is important for a precise label, counseling, and family planning. NCBI+2MalaCards+2

A classic genetic cause is mutation of the SCO2 gene, which disrupts COX assembly and leads to a severe cardio-encephalomyopathy with lactic acidosis and hypotonia. Other genes can cause a very similar picture, including TMEM70 (Complex V/ATP synthase assembly defect). These are part of the broad spectrum of mitochondrial diseases. ScienceDirect+3PubMed+3PMC+3

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Other names

1. Fatal infantile cardioencephalomyopathy (FICEM) – a term often used when the brain and heart are both affected with early, severe disease. Orpha

2. Cytochrome-c oxidase (COX) deficiency with cardiomyopathy – highlights the Complex IV enzyme problem in mitochondria. NCBI

3. CEMCOX1 / SCO2-related fatal infantile cardioencephalomyopathy – names used in rare-disease catalogs for the SCO2 subtype. National Organization for Rare Disorders+1

4. Mitochondrial encephalo-cardio-myopathy due to TMEM70 – emphasizes the TMEM70 gene subtype. Orpha

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Types

Because this is a syndrome pattern, doctors often classify by the gene or mitochondrial complex involved:

1. SCO2-related COX (Complex IV) deficiency – often severe, early cardiomyopathy, hypotonia, lactic acidosis. PubMed+1

2. COA5 / other COX-assembly defects – rare COX assembly genes can cause a similar infantile cardioencephalomyopathy. Orpha

3. TMEM70-related Complex V deficiency – neonatal hypotonia, hypertrophic cardiomyopathy, metabolic crises with lactic acidosis ± hyperammonemia. Orpha+1

4. Complex I defects (e.g., NDUFS/NDUFA genes) with infantile hypotonia and lactic acidosis, sometimes cardiomyopathy. PubMed

5. Other mitochondrial DNA or nuclear DNA defects causing early mitochondrial cardiomyopathy and lactic acidosis (broader mitochondrial spectrum). Frontiers

Note: Clinicians also talk about hypertrophic vs dilated cardiomyopathy phenotypes within this syndrome spectrum.

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Causes

Most causes are genetic and affect how mitochondria make energy. A few conditions outside mitochondria can mimic the same triad.

1. SCO2 mutations (COX assembly) – prevent proper Complex IV function; heart and muscle cells cannot use oxygen to make ATP, so lactate rises and muscles are weak. PubMed

2. COA5 and other COX-assembly gene defects – similar to SCO2; failure to assemble Complex IV leads to lactic acidosis and cardiomyopathy. Orpha

3. TMEM70 mutations (Complex V/ATP synthase) – defective ATP synthase assembly, causing energy shortage, lactic acidosis, hypotonia, and hypertrophic cardiomyopathy. Orpha+1

4. Complex I gene defects (e.g., NDUFS2) – reduce electron transfer early in the chain, causing energy failure and lactate build-up; hypotonia is common. PubMed

5. Complex III/IV/V combined assembly defects – multiple complex assembly problems can produce the same clinical triad in infancy. PMC

6. mtDNA mutations (e.g., certain tRNA or ND gene variants) – mitochondrial DNA errors impair oxidative phosphorylation across tissues including heart and muscle. PMC

7. Pyruvate dehydrogenase (PDH) complex defects – block entry of pyruvate into the Krebs cycle; pyruvate is shunted to lactate, causing lactic acidosis and hypotonia; cardiomyopathy can occur. PMC

8. Fatty-acid oxidation disorders (e.g., VLCAD deficiency) – the heart relies on fat for fuel; when beta-oxidation fails, cardiomyopathy and metabolic acidosis can occur with low tone. (Broader mitochondrial/energy failure workups include these.) ARUP Consult

9. Organic acidemias (propionic or methylmalonic acidemia) – toxic metabolites and energy failure can cause lactic acidosis and cardiomyopathy. (Included in metabolic differential during workup.) ARUP Consult

10. Barth syndrome (TAZ) – a mitochondrial lipid remodeling disorder with cardiomyopathy and muscle weakness; lactic acidosis may be seen during decompensation. (Part of mitochondrial cardiomyopathy spectrum.) Frontiers

11. TMEM70 variants with hyperammonemia – ammonia rise adds to the metabolic crisis, worsening lactic acidosis and weakness. PMC

12. COX copper-handling defects (e.g., failure of copper delivery to COX) – impair Complex IV activity and lead to lactic acidosis. BioMed Central

13. Other nuclear genes for mitochondrial translation/maintenance – impair many complexes at once, producing severe infantile disease with the triad. PMC

14. Complex V defects beyond TMEM70 – other ATP synthase assembly or structural genes can cause similar phenotypes. PMC

15. Combined oxidative phosphorylation deficiency syndromes – multiple Complex defects from a single gene cause global energy failure. PMC

16. Congenital lactic acidosis of unclear genotype – some neonates have clear mitochondrial lactic acidosis with hypotonia and cardiomyopathy before the exact gene is found. SAGE Journals

17. Secondary mitochondrial dysfunction from severe hypoxia/ischaemia in the newborn – can cause lactic acidosis and cardiac dysfunction that resembles the syndrome. (Differential diagnosis to exclude.) PMC

18. Sepsis-related mitochondrial failure – critical illness may drive lactic acidosis and myocardial depression; this must be ruled out during workup. (General mitochondrial evaluation guidance.) PMC

19. Drug-induced mitochondrial toxicity (e.g., rare cases with linezolid or certain antiretrovirals) – can raise lactate and weaken muscle/heart; important to consider if symptoms start after exposure. (General mitochondrial medicine resources note drug triggers.) PMC

20. Nutritional or endocrine precipitants in a genetically susceptible child – fasting, intercurrent infection, or dehydration can precipitate metabolic crises and unmask the triad. (Standard teaching in mitochondrial care statements.) Nature

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Symptoms

1. Poor feeding and weak suck – low muscle tone and easy fatigue make it hard to breast- or bottle-feed; weight gain is slow. Orpha

2. “Floppy” baby (hypotonia) – the infant feels soft when lifted, with poor head control because muscles lack energy. Pediatric Neurology Briefs

3. Fast breathing or labored breathing – lactic acidosis stimulates breathing; muscle weakness can also involve breathing muscles. SAGE Journals

4. Sweating, pallor, or cool skin with feeds – signs of heart strain when the heart is thick or weak. Orpha

5. Rapid heartbeat or irregular beats – cardiomyopathy can trigger arrhythmias. Orpha

6. Enlarged heart (cardiomegaly) – seen on exam or imaging when the heart muscle is thickened or dilated. Orpha

7. Lethargy and excessive sleepiness – cells cannot make enough ATP, so the child tires easily. SAGE Journals

8. Vomiting or poor tolerance to illness – metabolic stress raises lactate and worsens symptoms. PMC

9. Failure to thrive – poor feeding + high energy demand from illness lead to slow weight and length gain. Orpha

10. Developmental delay – rolling, sitting, and standing are late because muscles and sometimes the brain are affected. Orpha

11. Low stamina and exercise intolerance – even mild activity can cause heavy breathing and fatigue. PMC

12. Seizures (in some forms) – brain energy failure can trigger seizures or encephalopathy. Orpha

13. Hepatomegaly (enlarged liver) – sometimes the liver is enlarged in COX deficiency; in severe cases liver failure can occur. NCBI

14. Fevers or infections that cause sudden worsening – illness can precipitate metabolic decompensation with rising lactate. Nature

15. Peripheral weakness – limbs feel weak; older children may have trouble climbing or rising from the floor. PMC

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Diagnostic tests

A) Physical examination

1. General observation and growth check – doctors look for poor weight gain, lethargy, and signs of distress; these raise concern for systemic energy failure. PMC

2. Cardiac exam – listening for gallops or murmurs, checking pulses and perfusion to detect heart dysfunction. Orpha

3. Respiratory exam – fast breathing, retractions, or low oxygen suggest acidosis or respiratory muscle weakness. SAGE Journals

4. Neurologic tone and reflexes – low tone, head lag, and weak reflexes point to hypotonia and myopathy. PMC

5. Liver and abdomen exam – an enlarged liver can appear in COX deficiency. NCBI

B) Manual bedside functional tests

6. Manual Muscle Testing (MRC grading) – gentle resistance testing grades strength and tracks change over time. PMC

7. Head-lag and ventral suspension tests in infants – simple bedside checks for axial hypotonia. PMC

8. Gowers’ maneuver observation (in older children) – using hands to climb up the thighs indicates proximal weakness. PMC

9. Feeding/swallow assessment at the bedside – watches for weak suck or fatigue during feeds. PMC

10. Six-minute walk (when age-appropriate) – functional tolerance measure; early termination suggests energy failure. PMC

C) Laboratory and pathological tests

11. Blood lactate and pyruvate with lactate:pyruvate ratio – cornerstone tests; high lactate supports impaired oxidative metabolism, though values may be normal outside crises. PMC+1

12. Plasma amino acids and urine organic acids – screen for mitochondrial disease and for mimicking metabolic disorders (e.g., organic acidemias). ARUP Consult+1

13. Plasma acylcarnitine profile – screens for fatty-acid oxidation defects that can also present with cardiomyopathy and acidosis. ARUP Consult+1

14. Creatine kinase (CK), liver enzymes, ammonia – CK may be normal or mildly high; ammonia may rise during crises (especially TMEM70). PMC+1

15. Genetic testing panels / exome – targeted mitochondrial disease or cardiomyopathy panels (including SCO2, COA5, TMEM70, etc.) are now first-line; confirm the exact subtype. NCBI+1

16. Muscle biopsy (selected cases) – may show COX deficiency or mitochondrial changes; used less often now that genetics is widely available. PMC

D) Electrodiagnostic tests

17. Electrocardiogram (ECG) – checks rhythm problems and hypertrophy patterns linked to cardiomyopathy. umdf.org

18. Electromyography/nerve conduction (EMG/NCS) – helps distinguish myopathy from neuropathy; can be normal or show myopathic changes in mitochondrial disease. PMC

E) Imaging tests

19. Echocardiography – defines hypertrophic vs dilated cardiomyopathy, measures function, and guides care. umdf.org

20. Cardiac MRI (and sometimes brain MRI/MRS) – MRI shows muscle thickness and function; MR spectroscopy can show lactate peaks; brain MRI may reveal associated changes. PMC

Clinical practice notes: Modern guidelines recommend stepwise evaluation—start with careful history/exam and the basic metabolic panel (lactate, pyruvate, amino acids, urine organic acids, acylcarnitines), then proceed to genetic testing, reserving invasive tests like muscle biopsy for selected scenarios. PMC+1

Non-pharmacological treatments (therapies & other care)

1) Coordinated mitochondrial-cardiology care (multidisciplinary clinic).
A team with cardiology, neurology, genetics, nutrition, and physiotherapy builds one plan. Purpose: reduce emergencies, unify medication choices, and track growth, development, and heart status. Mechanism: integrated monitoring (EKG/echo/MRI), lab follow-up (lactate), early risk detection, prompt therapy changes, and family education to prevent decompensation. This approach is standard for complex mitochondrial disease with cardiomyopathy, because heart involvement is a major driver of outcomes in children. OUP Academic+1

2) Emergency plan & “sick-day” protocol.
Families keep a written plan for fevers, vomiting, fasting intolerance, and breathing or feeding problems. Purpose: avoid catabolism and shock that worsen lactic acidosis. Mechanism: fast access to glucose fluids, antiemetics, and acidosis checks; rapid escalation to hospital when red flags appear. Mitochondrial guidelines stress avoiding prolonged fasting and treating intercurrent illness early to limit lactate rise. PMC+1

3) Nutrition plan with frequent feeds.
Small, regular carbohydrate-containing meals (including overnight strategies) help avoid fasting hypoglycemia and lactate spikes. Purpose: keep energy supply steady. Mechanism: frequent glucose prevents reliance on anaerobic metabolism, lowering lactate production. Dietitians tailor calories, protein, and fat based on growth and heart failure status (fluid and sodium may be limited in edema). PMC

4) Cardiac rehabilitation & gentle physiotherapy.
Low-intensity, supervised activity maintains function without energy crashes. Purpose: preserve mobility, reduce deconditioning, and support quality of life. Mechanism: carefully dosed aerobic and range-of-motion work may improve mitochondrial efficiency and circulation while avoiding overexertion that can trigger lactic acidosis. PMC

5) Respiratory support strategies.
Hypotonia can weaken breathing. Purpose: ensure safe oxygen and CO₂ levels, especially during illness or sleep. Mechanism: positioning, airway clearance, non-invasive ventilation when indicated, and early treatment of respiratory infections reduce hypoxia (which otherwise worsens lactic acidosis). ScienceDirect

6) Vaccination & infection-prevention bundle.
Up-to-date vaccines (including influenza, RSV strategies where eligible) and hygiene reduce infection stress on mitochondria and the heart. Purpose: fewer metabolic crises. Mechanism: preventing fevers and sepsis lessens catabolism and acidosis; for some infants with significant cardiopulmonary vulnerability, RSV monoclonal prophylaxis can be considered individually. ScienceDirect

7) Cataract assessment and early vision support (for Sengers phenotype).
Some children have congenital cataracts. Purpose: protect vision and support development. Mechanism: ophthalmology follow-up, low-vision services, and, when appropriate, timely surgery (see surgeries section) improve functional outcomes. BioMed Central

8) Avoidance of mitochondrial “stressors.”
Purpose: reduce risk of metabolic decompensation. Mechanism: avoid prolonged fasting; minimize exposure to drugs known to stress mitochondria (e.g., some cases avoid valproate, linezolid) unless benefits clearly outweigh risks; use anesthetic plans mindful of mitochondrial disease. ScienceDirect

9) Palliative care integration.
For severe forms, palliative teams add symptom control, complex decision support, and family coping help—alongside disease-directed care. Purpose: improve comfort and alignment with family goals. Mechanism: structured conversations and symptom plans reduce crises and hospitalizations. ScienceDirect

10) Genetic counseling.
Purpose: clarify inheritance and recurrence risk, and discuss options for future pregnancies. Mechanism: review autosomal recessive patterns common to SLC25A3 and AGK variants; offer carrier testing for relatives. MalaCards+1

11) School and developmental supports.
Occupational, speech, and physical therapy services help with feeding, tone, and communication. Purpose: maximize development. Mechanism: task-specific training and adaptive tools reduce daily energy demand. ScienceDirect

12) Temperature and hydration management.
Purpose: prevent dehydration and fever-related catabolism. Mechanism: consistent fluids and prompt antipyretic strategies during illness can limit lactate production. PMC

13) Cardiac rhythm surveillance.
Purpose: catch arrhythmias early. Mechanism: periodic ECG/Holter in cardiomyopathy; arrhythmias may require drugs or devices. Surveillance is standard in HCM care. AHA Journals

14) Echocardiography/MRI schedule.
Purpose: track wall thickness, systolic/diastolic function, and scar. Mechanism: imaging guides medication titration and device or transplant timing. AHA Journals

15) Scoliosis and orthopedic monitoring.
Hypotonia can alter posture. Purpose: preserve breathing mechanics and comfort. Mechanism: bracing or surgery planning as needed. ScienceDirect

16) Safe anesthesia planning.
Purpose: minimize peri-operative metabolic stress. Mechanism: pre-op glucose, normothermia, careful agents, and close postoperative monitoring—all standard considerations in mitochondrial disease. ScienceDirect

17) Social work and home nursing support.
Purpose: reduce caregiver burden and ensure adherence. Mechanism: coordinate supplies, equipment, transport, and benefits. ScienceDirect

18) Lactate-trigger tracking and wearables (when practical).
Purpose: learn each child’s thresholds for exertion or illness. Mechanism: symptom diaries and simple wearables for HR/SpO₂ can cue rest and earlier intervention. ScienceDirect

19) Sleep optimization.
Purpose: better energy balance. Mechanism: treat sleep-disordered breathing and build consistent routines to lower daytime fatigue. ScienceDirect

20) Family training in signs of decompensation.
Purpose: speed up care when needed. Mechanism: teach red flags (fast breathing, feeding refusal, very sleepy, low urine, cold skin, new swelling). Early action reduces risk. ScienceDirect

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Drug treatments

Important: No drug “cures” CHLAS. These medicines treat heart failure, arrhythmias, and metabolic crises. Many uses in infants are off-label and must be individualized by specialists. FDA labels below establish class effects/indications and safety information; pediatric mitochondrial use depends on expert judgment.

1) Carvedilol (beta-blocker).
Purpose: treat heart failure symptoms and improve remodeling in some pediatric cardiomyopathies. Mechanism: blocks β-adrenergic stimulation, lowering heart rate and oxygen demand. Dose: pediatric titration is specialist-guided; adult starting dose is 3.125–6.25 mg BID with food, up-titrated as tolerated; liquid formulations may be used in children. Side effects: bradycardia, hypotension, fatigue; avoid in acute decompensation. FDA Access Data+1

2) Metoprolol or Propranolol (beta-blockers).
Purpose: slow heart rate and reduce outflow tract gradients in HCM; control arrhythmias. Mechanism: β-blockade improves diastolic filling and reduces ischemia. Dose: individualized; frequent monitoring. Side effects: bradycardia, fatigue, low blood pressure. (Use is guided by HCM guidelines.) AHA Journals+1

3) Lisinopril (ACE inhibitor).
Purpose: afterload reduction and neurohormonal blockade in systolic failure. Mechanism: inhibits angiotensin-converting enzyme. Dose (adults): 2.5–5 mg daily, titrate; pediatric dosing is weight-based and specialist-guided. Side effects: cough, hyperkalemia, kidney effects; boxed warning in pregnancy. FDA Access Data+1

4) Enalapril (including EPANED oral solution).
Purpose: ACE inhibitor option with pediatric-friendly liquid. Mechanism: RAAS blockade. Dose: EPANED 1 mg/mL allows precise mg/kg dosing. Side effects: similar to lisinopril; monitor potassium and renal function. FDA Access Data+1

5) Sacubitril/valsartan (ARNI).
Purpose: for heart failure with reduced EF in selected patients; pediatric data exist (PANORAMA-HF program). Mechanism: neprilysin inhibition + ARB. Dose: specialist-guided pediatric dosing; adult tablets BID. Side effects: hypotension, hyperkalemia, renal effects; contraindicated with ACEi within 36 h; fetal toxicity. FDA Access Data+2FDA Access Data+2

6) Furosemide.
Purpose: relieve edema and pulmonary congestion. Mechanism: loop diuretic increases sodium and water excretion. Dose: individualized; IV for acute settings, oral for maintenance. Side effects: electrolyte loss, dehydration, ototoxicity at high doses. FDA Access Data+1

7) Spironolactone (± Eplerenone).
Purpose: neurohormonal blockade and potassium-sparing diuresis. Mechanism: aldosterone antagonism. Dose: specialist-guided; monitor K⁺ and creatinine. Side effects: hyperkalemia; spironolactone can cause gynecomastia. FDA Access Data+1

8) Ivabradine.
Purpose: lowers sinus heart rate when beta-blockers are not enough or not tolerated; FDA-approved for pediatric DCM ≥6 months. Mechanism: selective If current blocker in SA node. Dose: weight-based pediatric dosing. Side effects: bradycardia, luminous phenomena, atrial fibrillation. FDA Access Data+2FDA Access Data+2

9) Dapagliflozin (SGLT2 inhibitor).
Purpose: in adults with HF, reduces CV death/HF hospitalization; pediatric experience is evolving. Mechanism: natriuresis, metabolic and renal effects that aid heart failure. Dose (adults): 10 mg daily. Side effects: genital infections, volume depletion; monitor kidney function. FDA Access Data+1

10) Milrinone (short-term inotrope).
Purpose: bridge therapy in decompensated HF or pre-/post-op. Mechanism: PDE-3 inhibition increases contractility and vasodilation. Dose: IV infusion in ICU only. Side effects: arrhythmias, hypotension. (FDA label supports use as inotrope; specialist setting essential.) AHA Journals

11) Amiodarone.
Purpose: treat serious ventricular or atrial arrhythmias. Mechanism: class III antiarrhythmic. Dose: loading then maintenance; pediatric dosing requires electrophysiology guidance. Side effects: thyroid, hepatic, pulmonary toxicity; many interactions. (Use guided by cardiology/EP and label warnings.) AHA Journals

12) Digoxin.
Purpose: rate control and modest inotropy in select children; avoid in obstructive HCM. Mechanism: Na⁺/K⁺-ATPase inhibition. Dose: weight-based with serum level monitoring. Side effects: arrhythmias, nausea; caution with renal dysfunction. (Per HF practice; follow label cautions.) AHA Journals

13) Sodium bicarbonate (IV).
Purpose: correct severe acidemia during shock while treating the cause; not for routine lactic acidosis. Mechanism: buffers H⁺, raises pH; may worsen CO₂ load. Dose: ICU-guided. Side effects: sodium load, alkalemia, hypokalemia. Pediatric data suggest nuanced, selective benefit. Medscape+2BioMed Central+2

14) Levocarnitine (L-carnitine).
Purpose: treat primary carnitine deficiency or secondary depletion; sometimes used in mitochondrial care. Mechanism: shuttles long-chain fatty acids into mitochondria. Dose: mg/kg divided, oral/IV. Side effects: GI upset, fishy odor; monitor for TMAO issues. (L-carnitine has FDA-labeled indications; use in CHLAS is individualized.) PMC

15) Loop + thiazide synergy (e.g., add chlorothiazide).
Purpose: diuretic resistance rescue. Mechanism: sequential nephron blockade to reduce edema. Dose: specialist-guided; watch electrolytes. Side effects: hypokalemia, hyponatremia. (Drug class effects supported by HF practice; check labels.) AHA Journals

16) ACEi/ARB alternatives (losartan).
Purpose: RAAS blockade when ACEi not tolerated. Mechanism: AT1 receptor blockade. Side effects: hyperkalemia, renal effects; pregnancy warning. (Label-based class cautions; pediatric dosing individualized.) AHA Journals

17) Diuretic adjuncts (metolazone).
Purpose: refractory edema. Mechanism: distal tubule diuresis. Side effects: marked electrolyte shifts; careful monitoring essential. (Label cautions and HF practice apply.) AHA Journals

18) Anticoagulation/antiplatelets when indicated.
Purpose: prevent thrombosis in certain cardiomyopathy settings (e.g., severe LV dysfunction, atrial fibrillation). Mechanism: inhibit clot formation. Dose: agent-specific; pediatric cardiology guided. Side effects: bleeding. (Use follows cardiology guidance and product labels; not routine for all CHLAS patients.) AHA Journals

19) Inhaled bronchodilators during intercurrent disease.
Purpose: ease work of breathing in viral wheeze/asthma that can drive lactic acidosis. Mechanism: airway smooth muscle relaxation. Side effects: tachycardia; monitor in HCM. (Use per pediatric standards and labels.) Medscape

20) Anti-infectives for sepsis/serious infections.
Purpose: promptly treat infections that trigger catabolism and acidosis. Mechanism: pathogen-directed antibiotics/antivirals per culture and local guidance. Side effects: drug-specific; avoid mitochondrial-toxic agents when alternatives exist. (Use is standard-of-care, label-informed, case-specific.) ScienceDirect

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Dietary molecular supplements

1) Coenzyme Q10 (ubiquinone/ubiquinol).
Function: cofactor in electron transport chain; antioxidant. Dose: often 5–30 mg/kg/day divided; some use higher in deficiency states. Mechanism: supports mitochondrial ATP production and reduces oxidative stress. Evidence: case series and small trials suggest symptomatic benefit in some mitochondrial myopathies; quality varies. PMC+1

2) Riboflavin (vitamin B2).
Function: precursor of FAD/FMNs for complex I/II. Dose: commonly 50–200 mg/day in divided doses. Mechanism: “pushes” flavoprotein-dependent steps in oxidative phosphorylation; clear benefit in some riboflavin-responsive defects. PMC

3) Thiamine (vitamin B1).
Function: cofactor for pyruvate dehydrogenase. Dose: 50–200 mg/day oral; higher IV in crises. Mechanism: helps move pyruvate into the TCA cycle, potentially lowering lactate. PMC

4) Alpha-lipoic acid.
Function: antioxidant and cofactor for mitochondrial dehydrogenases. Dose: 50–200 mg/day children are individualized; adult 300–600 mg/day used in neuropathy. Mechanism: redox cycling and PDH complex support. PMC

5) Creatine monohydrate.
Function: energy buffer in muscle. Dose: pediatric regimens vary; adult 3–5 g/day commonly used. Mechanism: phosphocreatine system smooths ATP demand during exertion. PMC

6) L-arginine or L-citrulline.
Function: nitric oxide substrate; used in some mitochondrial stroke-like episodes and perfusion issues. Dose: weight-based; specialist protocols. Mechanism: improves endothelial function and blood flow; may reduce lactic burden indirectly. PMC

7) NAD⁺ precursors (niacinamide).
Function: supports NAD⁺ pools for dehydrogenases. Dose: individualized; monitor liver enzymes. Mechanism: boosts redox capacity. PMC

8) Omega-3 fatty acids.
Function: anti-inflammatory; may aid cardiac function. Dose: 20–100 mg/kg/day EPA+DHA equivalents in pediatrics; tailor to age. Mechanism: membrane effects, anti-inflammatory signaling. PMC

9) Vitamin D.
Function: bone and muscle support. Dose: per age/level; replete deficiency. Mechanism: muscle function and immune modulation; indirect benefit. PMC

10) Magnesium.
Function: cofactor for ATP-dependent enzymes; helps with cramps/arrhythmias when low. Dose: adjust to serum levels; pediatric mg/kg dosing. Mechanism: stabilizes ATP and electrophysiology. PMC

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Immunity-booster / regenerative / stem-cell drugs

1) Palivizumab (RSV monoclonal) for eligible infants.
Use: reduce RSV hospitalization risk in vulnerable infants with significant cardiopulmonary disease. Dosing: monthly during season. Function: passive immunity to RSV F protein. Mechanism: neutralizes RSV, lowering infection risk and metabolic stress. (Eligibility is individualized.) ScienceDirect

2) Intravenous immunoglobulin (IVIG).
Use: in documented humoral immunodeficiency or specific indications; not a routine “booster.” Function: pooled antibodies. Mechanism: broad passive immunity; reduces severe infection risk when indicated. Dosing: per product label/indication. ScienceDirect

3) Epoetin alfa.
Use: treat symptomatic anemia (select cases), improving oxygen delivery. Function: stimulates erythropoiesis. Mechanism: higher hemoglobin improves tissue oxygenation and reduces anaerobic metabolism. Dosing: weight-based per label. AHA Journals

4) Experimental mesenchymal stem cell (MSC) therapy for cardiomyopathy (research only).
Use: investigational in pediatric cardiomyopathies. Function: paracrine support. Mechanism: cytokines may aid remodeling. Dosing: clinical-trial protocols only; not standard of care. AHA Journals

5) Elamipretide (SS-31; investigational).
Use: research peptide that targets cardiolipin to stabilize mitochondria. Mechanism: may improve electron transport efficiency. Dosing: trial-specific; not FDA-approved for CHLAS. PMC

6) Vatiquinone (EPI-743; investigational).
Use: antioxidant/redox modulator studied in mitochondrial disease. Mechanism: targets NAD(P)H:quinone oxidoreductase pathways. Not FDA-approved; dosing only in trials. PMC

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Surgeries / procedures

1) Early cataract extraction (Sengers phenotype).
Procedure: remove cloudy lens; often with intraocular lens placement. Why: improve visual input for development when cataracts are dense. Timing is individualized by pediatric ophthalmology. BioMed Central

2) Implantable cardioverter-defibrillator (ICD).
Procedure: device placed under skin with leads to heart. Why: prevent sudden death from dangerous ventricular arrhythmias in selected high-risk cardiomyopathy patients per guidelines. AHA Journals

3) Permanent pacemaker.
Procedure: device to maintain safe heart rate when conduction is too slow. Why: treat clinically significant bradyarrhythmias or heart block that worsen perfusion. AHA Journals

4) Left ventricular assist device (LVAD).
Procedure: mechanical pump supports circulation. Why: bridge to transplant or destination therapy in end-stage heart failure when feasible in pediatric centers. AHA Journals

5) Heart transplantation.
Procedure: replace failing heart. Why: for refractory heart failure when other options fail and when overall prognosis and extracardiac disease burden allow. Outcomes depend on systemic disease severity. AHA Journals

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Prevention tips

1. Avoid prolonged fasting; use frequent feeds and sick-day glucose plans to limit lactate. PMC

2. Keep vaccines up to date and follow infection-prevention habits at home and school. ScienceDirect

3. Treat fevers and infections early to avoid catabolic crises. ScienceDirect

4. Regular cardiology follow-up with ECG/echo/MRI to anticipate problems. AHA Journals

5. Medication review at every visit to avoid agents that can stress mitochondria when reasonable alternatives exist. ScienceDirect

6. Hydration and electrolyte plans during illness and hot weather. PMC

7. Sleep and respiratory support to prevent hypoxia-driven lactate rises. ScienceDirect

8. Genetic counseling for family planning. MalaCards

9. Emergency information card for caregivers and schools with clear escalation steps. ScienceDirect

10. Structured, gentle activity instead of sudden intense exercise bouts. PMC

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When to see a doctor urgently

Seek urgent care for fast, heavy breathing; blue or pale skin; poor feeding or vomiting; new swelling; fainting; very sleepy or hard to wake; fever not settling; sudden drop in urine; or any new chest pain, palpitations, or fainting spells. In a known cardiomyopathy, these can signal decompensated heart failure or a metabolic crisis and need immediate evaluation with labs, ECG, and possible IV support. Medscape

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What to eat and what to avoid

What to eat: regular, balanced meals with reliable carbohydrate at each feed; adequate protein for growth and muscle repair; fruits/vegetables for micronutrients; and fluids spaced through the day. Some centers suggest bedtime snacks or overnight feeds to prevent fasting. Tailor sodium and fluids if edema is present under cardiology guidance. PMC

What to avoid: long gaps without food; crash dieting; energy drinks or high-dose caffeine; unsupervised “mega-doses” of supplements; dehydration; and, when alternatives exist, medicines known to stress mitochondria or worsen cardiomyopathy. Always check drug changes with the care team. ScienceDirect

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Frequently asked questions

1) Is CHLAS the same condition in every child?
No. It is a pattern that can come from different mitochondrial gene problems (e.g., SLC25A3, AGK), so severity and extra features vary. MalaCards+1

2) Why is lactate high?
Damaged mitochondria push cells to make more energy without oxygen (anaerobic glycolysis), which produces lactate. ScienceDirect

3) Will the heart always be thick (HCM)?
Many infants have hypertrophic cardiomyopathy; some evolve to dilation or mixed pictures. Ongoing imaging shows the trend. AHA Journals

4) Can medicines cure CHLAS?
No. Medicines treat heart failure, rhythm issues, and crises; supplements support energy. Care is long-term and individualized. AHA Journals+1

5) Are there proven “mitochondrial cocktails”?
CoQ10 and B-vitamins are commonly used, but evidence quality varies. Use what your specialist recommends and monitor. PMC

6) Do we need a feeding plan even when well?
Yes—regular meals and sick-day plans prevent fasting-related lactate spikes. PMC

7) Is genetic testing important?
Yes. It can pinpoint the gene, inform prognosis, guide family testing, and support decisions. NCBI

8) Can my child play?
Yes—gentle, supervised activity is encouraged. Avoid overexertion that brings symptoms. PMC

9) Do we need routine echo and ECG?
Yes. Surveillance finds function changes or arrhythmias early so treatment can be adjusted. AHA Journals

10) Are bicarbonate infusions routine for lactic acidosis?
No. They may be used in severe acidemia with shock while fixing the cause; routine use shows limited benefit. Medscape+1

11) Can SGLT2 inhibitors help kids with cardiomyopathy?
Evidence is strong in adults; pediatric use is evolving and specialist-led. Risks and benefits must be weighed. FDA Access Data

12) When is surgery needed for cataracts?
When vision is significantly blocked; timing is individualized by pediatric ophthalmology. BioMed Central

13) Will my other children be affected?
Risk depends on the gene and inheritance—often autosomal recessive. Genetic counseling explains your family’s risk. MalaCards

14) Is transplant possible?
Sometimes, if extracardiac disease is manageable and overall prognosis supports it. A transplant team evaluates carefully. AHA Journals

15) What improves long-term outlook?
Early diagnosis, steady nutrition, infection prevention, careful heart failure care, and fast treatment of crises. OUP Academic+1

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

Last Updated: November 11, 2025.

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