Barth Syndrome

Barth syndrome is a rare genetic condition that mostly affects boys. It is caused by changes (mutations) in a gene called TAFAZZIN (TAZ) on the X chromosome. This gene helps make and repair a special fat in the inner membrane of mitochondria called cardiolipin. Cardiolipin keeps the cell’s power plants working well. When TAFAZZIN does not work, cardiolipin stays immature and a related fat called monolysocardiolipin (MLCL) builds up. Because of this, many cells do not make energy well. The heart and skeletal muscles get tired and weak. The number of white blood cells called neutrophils can be too low, so infections happen more easily. Growth can be slow. Symptoms often start in infancy and may include heart failure, weak muscles, feeding problems, and frequent infections. The condition is X-linked, so it mainly affects males, though female carriers can very rarely have symptoms. Diagnosis is confirmed by a high MLCL:CL (monolysocardiolipin to cardiolipin) ratio and by finding a TAZ mutation. Management focuses on heart care, infection prevention, nutrition, and energy support. In September 2025, the FDA granted accelerated approval to Forzinity (elamipretide), the first therapy specifically approved for Barth syndrome. U.S. Food and Drug Administration+4NCBI+4rarediseases.info.nih.gov+4

Barth syndrome (BTHS) is a rare, inherited disorder (almost always in males) caused by disease-causing variants in the TAZ gene. TAZ encodes tafazzin, an enzyme that remodels cardiolipin, a key phospholipid that keeps the inner membrane of mitochondria working properly. When tafazzin doesn’t work, cardiolipin becomes abnormal, which impairs energy production and affects the heart muscle (cardiomyopathy, often including left-ventricular non-compaction), skeletal muscle (weakness, fatigue), white blood cells (especially neutropenia, increasing infection risk), and growth (short stature or delayed growth). Diagnosis rests on clinical features, genetic testing, and a characteristic elevated monolysocardiolipin:cardiolipin ratio. Management is multidisciplinary: cardiology for heart failure, hematology for neutropenia, infectious-disease for infection prevention/treatment, nutrition/rehab for stamina and growth, and genetics for family counseling. MDPI+4NCBI+4rarediseases.info.nih.gov+4

Other names

Barth syndrome is also known as: BTHS, TAZ deficiency, TAFAZZIN deficiency, cardiolipin remodeling disorder, 3-methylglutaconic aciduria type II (MGA type II), and older terms such as X-linked cardioskeletal myopathy with neutropenia or lethal infantile cardiomyopathy (LIC) in severe infant cases. These names reflect the gene involved (TAZ), the lipid problem (cardiolipin), and the organic acid seen in urine (3-methylglutaconic acid). MedlinePlus+1

Types

Doctors do not use strict “types,” but several patterns are common. Thinking in patterns helps families and clinicians recognize the condition early:

1. Infant cardiomyopathy pattern. Babies can present with dilated cardiomyopathy and heart failure in the first months of life; some have endocardial fibroelastosis or left ventricular noncompaction (LVNC). NCBI

2. Childhood myopathy-dominant pattern. Some children have milder heart findings but clear skeletal muscle weakness, poor stamina, and exercise intolerance. National Organization for Rare Disorders

3. Neutropenia-dominant or infection-prone pattern. Recurrent mouth ulcers, gingivitis, skin infections, and fevers due to persistent, intermittent, or cyclical neutropenia. PMC

4. Growth-delay pattern. Children may have low weight and height with later “catch-up” after puberty. NCBI

5. Mixed pattern with LVNC. Prominent trabeculations on echo or cardiac MRI with variable pumping function. NCBI

6. Adolescent/adult survivors. Better heart function after infancy but ongoing fatigue, weakness, and infections. National Organization for Rare Disorders

7. Variable female carriers (rare). Most are asymptomatic; rare cases show mild features due to skewed X-inactivation. NCBI

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Causes

Below, “causes” are broken down into the genetic root cause, the biochemical defect, and the downstream cellular/organ effects that create the clinical picture. Each item explains what it is and how it contributes.

1. TAFAZZIN (TAZ) gene mutation (X-linked). Pathogenic variants (missense, nonsense, frameshift, splice, deletions) reduce or abolish tafazzin enzyme activity. This is the primary cause of the syndrome. MedlinePlus

2. Faulty cardiolipin remodeling. Tafazzin normally adds the right fatty acids to cardiolipin. When it fails, cardiolipin stays immature and dysfunctional. PMC

3. Monolysocardiolipin (MLCL) accumulation. MLCL builds up because it is not properly reacylated, giving a high MLCL:CL ratio, the biochemical hallmark used in diagnosis. PMC

4. Mitochondrial membrane instability. Abnormal cardiolipin disrupts cristae structure, membrane curvature, and protein complex assembly, weakening energy production. PMC

5. Impaired oxidative phosphorylation. Respiratory chain “supercomplexes” rely on cardiolipin; their disruption lowers ATP output, causing fatigue and myopathy. PMC

6. Altered mitophagy and quality control. Defective cardiolipin signaling affects mitophagy, leading to accumulation of unhealthy mitochondria. PMC

7. Reactive oxygen species imbalance. Disturbed electron transport increases oxidative stress, damaging muscle and heart cells. PMC

8. Sarcomere and calcium handling changes. Energy shortage and membrane defects disturb contraction and relaxation in heart and skeletal muscle. PMC

9. Cardiac development effects (LVNC/DFE). Mitochondrial dysfunction during fetal development can lead to left ventricular noncompaction or endocardial fibroelastosis. NCBI

10. Neutrophil survival or turnover problems. The exact mechanism of neutropenia is debated (e.g., apoptosis/clearance), but low counts are frequent and episodic. BioMed Central

11. Abnormal lipid signaling. Cardiolipin influences many signaling pathways; its loss alters cellular stress responses. PMC

12. Energy deficit in fast-twitch muscle. High-demand fibers fatigue early, causing exercise intolerance. PMC

13. Cardiomyocyte remodeling and fibrosis. Chronic stress remodels the heart, risking dilatation, arrhythmias, and heart failure. NCBI

14. Feeding difficulty–related under-nutrition. Poor energy and oral motor issues can worsen growth failure. PMC

15. Immune vulnerability from neutropenia. Mouth, skin, and respiratory infections occur more easily and may reveal the diagnosis. Barth Syndrome Foundation

16. Metabolite abnormalities (3-methylglutaconic acid). Many patients have high 3-MGA in urine; it signals mitochondrial dysfunction. MedlinePlus

17. Abnormal membrane biophysics. Changes in lipid composition alter membrane fluidity and protein function across tissues. PMC

18. System-wide lipidome shifts. Broad lipid remodeling affects multiple organs, not just the heart and muscle. PMC

19. Gene–variant spectrum and residual function. Different TAZ variants lead to variable enzyme activity and explain the wide range of symptom severity. MedlinePlus

20. Developmental timing. Mitochondrial stress during fetal and early infant life shapes severity at birth versus later childhood. NCBI

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Common symptoms and signs

1. Breathlessness or fast breathing in babies. Weak heart pumping can cause rapid breathing and trouble feeding. NCBI

2. Heart failure signs. Poor feeding, sweating during feeds, swelling, or poor weight gain may reflect low cardiac output. NCBI

3. Dilated cardiomyopathy or LV noncompaction. The heart looks enlarged and pumps weakly; sometimes the muscle has a spongy look (LVNC). NCBI

4. Arrhythmias or abnormal ECG. Conduction problems and rhythm issues can occur because stressed heart cells conduct electricity differently. PMC

5. Skeletal muscle weakness. Children tire quickly, have low endurance, and may be late to sit, stand, or walk. National Organization for Rare Disorders

6. Exercise intolerance. Walking, running, or climbing stairs may feel hard due to low energy production in muscle. National Organization for Rare Disorders

7. Neutropenia and infections. Recurrent mouth ulcers, gum disease, skin infections, and fevers are common. Counts can vary over time. PMC

8. Growth delay and short stature. Many boys are smaller before puberty; some catch up later. NCBI

9. Feeding problems in infancy. Weakness and heart symptoms make feeding difficult, leading to poor weight gain. PMC

10. Fatigue and low stamina. Daily activities feel tiring because muscles cannot sustain effort. PMC

11. Characteristic facial features in infancy. Some babies have a recognizable facial appearance, though this becomes less obvious with age. NCBI

12. Learning challenges (mild). Some children have mild learning or attention issues; many attend mainstream school. National Organization for Rare Disorders

13. Elevated 3-methylglutaconic acid. This lab finding reflects mitochondrial dysfunction and supports the diagnosis. MedlinePlus

14. Low muscle mass. Muscles may look small and feel weak, especially in the legs and shoulders. Stealth BioTherapeutics Inc.

15. Variable severity over life. Some infants are critically ill; others have milder heart signs but persistent fatigue and infections. National Organization for Rare Disorders

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Diagnostic tests

A) Physical examination (bedside)

1. General growth check. Height, weight, and head size are plotted to show growth delay or failure to thrive. This helps track nutrition and energy status over time. NCBI

2. Cardiac auscultation. The doctor listens for gallops, murmurs, or extra sounds that suggest dilated cardiomyopathy or valve leakage. NCBI

3. Heart failure signs. Rapid breathing, liver enlargement, cool extremities, or swelling suggest low cardiac output in infants and children. NCBI

4. Muscle bulk and tone. Observation and palpation can show low muscle mass, hypotonia, or proximal weakness typical of mitochondrial myopathy. PMC

5. Oral and skin inspection for infection. Mouth ulcers, gingivitis, and skin pustules may indicate neutropenia and guide urgent blood counts. Barth Syndrome Foundation

B) Manual/functional tests (simple clinic-based performance tests)

6. Manual muscle testing. The clinician checks strength against resistance at shoulders, hips, knees, and ankles to document proximal weakness. PMC

7. Gowers’ maneuver observation. Watching how a child stands up from the floor helps detect proximal weakness seen in metabolic myopathies. PMC

8. Timed up-and-go / 10-meter walk. Simple timed walking tests capture endurance and fatigue in a repeatable way during follow-up. PMC

9. Hand-grip dynamometry. A handheld device measures grip strength and changes with therapy or illness. PMC

10. Six-minute walk test (6MWT). Distance walked in six minutes reflects whole-body endurance; it is often paired with muscle strength measures in studies and trials. Reuters

C) Laboratory and pathological tests

11. Complete blood count with differential. Confirms neutropenia (low absolute neutrophil count) and monitors recovery or cycling patterns over weeks. PMC

12. Urine organic acids (3-MGA). Many patients show 3-methylglutaconic aciduria; this supports but does not by itself prove the diagnosis. MedlinePlus

13. Cardiolipin profile (MLCL:CL ratio) by mass spectrometry. A high MLCL:CL ratio is highly sensitive and specific for Barth syndrome and can be done on dried blood spots or leukocytes. PMC+1

14. TAFAZZIN (TAZ) gene sequencing. Identifies the causal variant; over 130 disease-causing variants have been reported. MedlinePlus

15. Broader exome/genome testing (if phenotype unclear). Helps detect atypical or de novo variants and rule out other mitochondrial disorders. PMC

D) Electrodiagnostic and electrophysiologic tests

16. Electrocardiogram (ECG). Looks for arrhythmias, conduction delays, or signs of ventricular enlargement that accompany cardiomyopathy. PMC

17. Holter monitoring or event recorder. Detects intermittent rhythm problems that a single ECG might miss. This can explain fainting, palpitations, or fatigue spells. PMC

18. Electromyography (EMG) and nerve conduction studies (NCS) (selected cases). May show a myopathic pattern when weakness is prominent and diagnosis is uncertain. PMC

E) Imaging tests

19. Echocardiography. Ultrasound assesses heart size, pumping function, valves, and may show LV noncompaction or endocardial fibroelastosis. It is central to diagnosis and follow-up. NCBI

20. Cardiac MRI. Provides detailed images of heart muscle structure, function, and fibrosis, and better defines LVNC when echo is unclear. Chest X-ray may show an enlarged heart in infants with heart failure. PMC

Non-pharmacological treatments (therapies & others)

1. Specialist heart-failure clinic follow-up
   Regular reviews with a pediatric or adult heart-failure team keep track of heart pumping function, rhythm, and symptoms. This helps catch problems early and adjust medicines or devices before a crisis. Mechanism: proactive monitoring of ejection fraction, rhythm, and congestion reduces decompensation risk and hospitalizations. PMC+1

2. Individualized exercise/physiotherapy
   Supervised low-to-moderate activity (walking, cycling, light resistance) improves stamina and muscle strength without overtaxing the heart. Purpose: better endurance and daily function; Mechanism: gradual conditioning improves mitochondrial efficiency and peripheral muscle use of oxygen, with careful pacing to avoid post-exercise crashes. PMC

3. Energy-conservation training
   Occupational therapy teaches pacing (rest breaks, planning), body-mechanics, and task simplification. Purpose: get through school/work/home life with fewer “energy crashes.” Mechanism: spreads energy use across the day to match limited ATP production from impaired mitochondria. PMC

4. Nutrition optimization
   Dietitians focus on adequate calories and protein, salt/fluid tailored to heart failure, and growth needs. Purpose: maintain weight and muscle while not worsening fluid retention. Mechanism: macronutrient balance and sodium-aware planning support cardiac and muscle metabolism. rarediseases.info.nih.gov

5. Infection-prevention hygiene
   Hand hygiene, prompt wound care, and avoiding sick contacts lower infections during neutropenia. Purpose: fewer fevers/hospitalizations; Mechanism: reduces microbe exposure while white cells are low. (Antibiotics/filgrastim appear later under drugs.) rarediseases.info.nih.gov

6. Up-to-date vaccines
   Routine immunizations (including influenza and pneumococcal per local schedules) protect against severe infections that can destabilize the heart. Mechanism: priming the immune system reduces infection risk when neutrophils dip. (Specific schedules are individualized by clinicians.) rarediseases.info.nih.gov

7. Emergency action plan
   Families keep a written plan (fever thresholds, when to go to the ER, what to tell triage, contact numbers). Purpose: fast, appropriate care for fever or worsening breathing; Mechanism: reduces delays and errors in emergencies. Barth Syndrome Foundation

8. School/college accommodations
   Extra time, rest breaks, modified physical education, and reduced lifting help participation. Mechanism: aligns workload with limited stamina and prevents symptom flares. rarediseases.info.nih.gov

9. Sleep optimization
   Consistent sleep improves daytime energy and heart health. Mechanism: restorative sleep supports autonomic balance and muscle recovery. PMC

10. Heat management
    Avoiding overheating and staying hydrated helps because impaired mitochondria and heart function make heat intolerance worse. Mechanism: limits circulatory strain and dehydration-induced tachycardia. PMC

11. Psychosocial support
    Counseling and peer groups (e.g., patient foundations) reduce anxiety and isolation; this improves adherence and quality of life. Mechanism: coping strategies reduce stress-related symptom worsening. Barth Syndrome Foundation

12. Genetic counseling
    Explains X-linked inheritance, carrier testing for relatives, and reproductive options. Mechanism: informed family planning and early detection in newborns at risk. NCBI

13. Rhythm monitoring
    Ambulatory ECG monitoring tracks arrhythmias common in cardiomyopathy/LV non-compaction. Purpose: detect treatable rhythm issues early. Mechanism: leads to timely antiarrhythmic strategies or device therapy. PMC+1

14. Dental/oral care
    Meticulous dental hygiene and quick management of mouth sores reduce bacteremia risk during neutropenia. Mechanism: lowers infection entry points. rarediseases.info.nih.gov

15. Sun-safe & skin care
    Gentle skin care avoids breaks that can invite bacterial infections when neutrophils are low. Mechanism: fewer portals of entry. rarediseases.info.nih.gov

16. Growth and puberty monitoring
    Tracking height/weight and endocrine evaluations help address delayed growth. Mechanism: early nutrition/endocrine support improves outcomes. rarediseases.info.nih.gov

17. Avoiding unnecessary central lines
    Because neutropenia raises infection risk, clinicians try to minimize long-term central venous access unless essential. Mechanism: fewer line infections. rarediseases.info.nih.gov

18. Heart-failure self-care education
    Daily weights, swelling checks, and symptom diaries enable early diuretic/medication adjustments. Mechanism: prevents decompensation. JACC

19. Multidisciplinary care conferences
    Cardiology, hematology, ID, rehab, nutrition, and genetics meet together to align the plan. Mechanism: reduces conflicting advice and care gaps. PMC

20. Clinical-trial awareness (gene therapy or mitochondrial-targeted agents)
    Families may discuss trials (e.g., AAV-TAZ gene replacement, mitochondrial agents) with specialists. Mechanism: potential access to investigational therapies while contributing to knowledge. PMC+1

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Drug treatments

Important: Only Forzinity (elamipretide) is FDA-approved specifically for Barth syndrome as of (accelerated approval). All others are standard-of-care drugs used for BTHS-related heart failure, arrhythmia, or infection/neutropenia management; dosing is individualized by clinicians. U.S. Food and Drug Administration+2Reuters+2

1. Elamipretide (FORZINITY) – the first FDA-approved BTHS drug
   Class: Mitochondria-targeted peptide. Typical use/dose: Subcutaneous injection once daily in patients ≥30 kg; exact dose per label. Purpose: Improve muscle strength; part of long-term BTHS management. Mechanism: Binds cardiolipin in the inner mitochondrial membrane, stabilizing cristae, enhancing electron transport and ATP production, and reducing oxidative stress. Side effects: Injection-site reactions, headache, nausea; ongoing post-marketing studies must confirm clinical benefit (accelerated approval). U.S. Food and Drug Administration+1

2. Sacubitril/valsartan (ENTRESTO/ENTRESTO SPRINKLE)
   Class: ARNI (neprilysin inhibitor + ARB). Dose/time: Twice daily; pediatric sprinkle option available. Purpose: Standard heart-failure therapy to reduce CV death/hospitalizations; in BTHS, used off-label to support LV dysfunction. Mechanism: Enhances natriuretic peptides (vasodilation/diuresis) and blocks angiotensin II. Side effects: Hypotension, hyperkalemia, renal issues; avoid in pregnancy. FDA Access Data+1

3. Enalapril (VASOTEC)
   Class: ACE inhibitor. Dose: Once/twice daily; titrated. Purpose: Foundational HF therapy to reduce afterload and adverse remodeling. Mechanism: Blocks ACE, lowering angiotensin II and aldosterone. Side effects: Cough, hyperkalemia, renal function changes, rare angioedema. FDA Access Data

4. Losartan (COZAAR)
   Class: ARB. Dose: Daily; alternative if ACE-inhibitor cough/angioedema. Purpose: HF and hypertension support. Mechanism: Blocks AT1 receptor signaling. Side effects: Dizziness, hyperkalemia; avoid with aliskiren in diabetes; pregnancy warning. FDA Access Data

5. Carvedilol (COREG)
   Class: Non-selective β-blocker with α1 block. Dose: Twice daily; slow titration. Purpose: Improves survival in HF and controls heart rate. Mechanism: Reduces sympathetic drive and oxygen demand. Side effects: Bradycardia, hypotension, fatigue. FDA Access Data+1

6. Metoprolol succinate (TOPROL-XL)
   Class: β1-selective blocker. Dose: Once daily extended-release; pediatric labeling exists for hypertension and dosing guidance. Purpose: HF and rate control when carvedilol not tolerated. Mechanism: Lowers heart rate and myocardial oxygen demand. Side effects: Bradycardia, fatigue. FDA Access Data+1

7. Ivabradine (CORLANOR)
   Class: If-channel inhibitor. Dose: Oral solution/tablet; dose per HR and age. Purpose: For symptomatic HF with elevated heart rate despite β-blocker or intolerance. Mechanism: Slows sinus node firing without lowering blood pressure. Side effects: Bradycardia, luminous phenomena (phosphenes), conduction issues. FDA Access Data+1

8. Spironolactone (ALDACTONE)
   Class: Mineralocorticoid receptor antagonist. Dose: Daily; monitor potassium. Purpose: HF mortality/morbidity benefit; counters aldosterone effects. Mechanism: Blocks aldosterone-mediated sodium/water retention and fibrosis. Side effects: Hyperkalemia, renal issues, gynecomastia. FDA Access Data

9. Eplerenone (INSPRA)
   Class: Selective MRA. Dose: Daily; often used if spironolactone side effects occur. Purpose: Similar HF benefits with less endocrine effect. Mechanism: Blocks aldosterone more selectively. Side effects: Hyperkalemia; CYP3A4 interactions. FDA Access Data+1

10. Furosemide (LASIX)
    Class: Loop diuretic. Dose: Variable oral/IV; titrate to euvolemia. Purpose: Relieve congestion (edema, breathlessness). Mechanism: Blocks NKCC2 in loop of Henle to increase urine output. Side effects: Electrolyte loss, dehydration, ototoxicity (high IV doses). FDA Access Data+1

11. Bumetanide (BUMEX)
    Class: Loop diuretic. Dose: Oral/IV; sometimes better oral bioavailability than furosemide. Purpose/Mechanism: Same as furosemide; used when response is inadequate. Side effects: Similar electrolyte issues; adjust carefully. FDA Access Data

12. Hydrochlorothiazide (MICROZIDE/HCTZ)
    Class: Thiazide diuretic. Dose: Daily; often add-on to loop diuretics. Purpose: Synergistic diuresis in resistant edema. Mechanism: Blocks NaCl reabsorption in distal tubule. Side effects: Low sodium/potassium, higher uric acid. FDA Access Data

13. Digoxin (LANOXIN)
    Class: Cardiac glycoside. Dose: Carefully weight-/renal-adjusted; pediatric loading guidelines exist. Purpose: Rate control and symptom relief in HF or certain arrhythmias. Mechanism: Inhibits Na⁺/K⁺-ATPase to increase intracellular calcium and inotropy. Side effects: Narrow therapeutic window—nausea, arrhythmias, visual changes. FDA Access Data

14. Dapagliflozin (FARXIGA)
    Class: SGLT2 inhibitor. Dose: Once daily; HF benefit shown in adults (with/out diabetes). Purpose: Add-on HF therapy to reduce hospitalization/CV death; pediatric data for HF are evolving. Mechanism: Natriuresis/osmotic diuresis; improved cardiac/renal signaling. Side effects: Genital infections, volume depletion—pediatric use in BTHS is specialist-directed. FDA Access Data+1

15. Filgrastim (NEUPOGEN)
    Class: G-CSF (granulocyte colony-stimulating factor). Dose: Subcutaneous; intermittent or PRN for neutropenia under hematology guidance. Purpose: Raise neutrophils to prevent or shorten infections. Mechanism: Stimulates bone marrow neutrophil production. Side effects: Bone pain, leukocytosis, rare splenic issues. FDA Access Data+1

16. Pegfilgrastim (NEULASTA)
    Class: Long-acting G-CSF. Dose: Single dose per cycle in oncology; BTHS dosing is individualized off-label when used. Purpose/Mechanism: Same as filgrastim with longer duration. Side effects: Similar to filgrastim. FDA Access Data

17. Amoxicillin (AMOXIL)
    Class: Aminopenicillin antibiotic. Dose: Weight-based; used for suspected/confirmed bacterial infections per culture/site. Purpose: Treat common community pathogens in neutropenic or post-viral settings. Mechanism: Inhibits bacterial cell-wall synthesis. Side effects: Allergy, GI upset; stewardship essential. FDA Access Data+1

18. Amoxicillin/clavulanate (AUGMENTIN)
    Class: β-lactam + β-lactamase inhibitor. Dose: Weight-based; food improves tolerance. Purpose: Broader outpatient coverage for sinusitis, skin/soft tissue, etc. Mechanism: Cell-wall inhibition plus β-lactamase blockage. Side effects: Diarrhea, rash. FDA Access Data

19. Azithromycin (ZITHROMAX)
    Class: Macrolide. Dose: Once-daily short courses; site-specific. Purpose: Treat atypical respiratory pathogens; sometimes used if penicillin allergy. Mechanism: Inhibits bacterial protein synthesis (50S ribosome). Side effects: GI upset, rare QT prolongation. FDA Access Data+1

20. Ceftriaxone (ROCEPHIN)
    Class: Third-generation cephalosporin (IV/IM). Dose: Weight-based; used for serious infections or febrile neutropenia per protocols. Mechanism: Cell-wall inhibition with broad Gram-negative/positive coverage. Side effects: Biliary sludging, diarrhea; stewardship required. FDA Access Data+1

Notes: Drug choices/doses for BTHS are individualized. Many above are standard HF or anti-infective agents used off-label in BTHS; only elamipretide (Forzinity) currently carries an FDA indication specifically for Barth syndrome. U.S. Food and Drug Administration+1

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Dietary molecular supplements

1. Coenzyme Q10 (ubiquinone) – 100–300 mg/day divided. Supports electron transport; may modestly improve perceived stamina in mitochondrial disorders. Evidence mixed. PMC

2. Riboflavin (vitamin B2) – 50–200 mg/day. Cofactor for complex I/II; sometimes tried in mitochondrial myopathy for energy support. PMC

3. Thiamine (vitamin B1) – 50–200 mg/day. Cofactor in pyruvate dehydrogenase; may support carbohydrate oxidation. PMC

4. Taurine – 500–1500 mg/day. Osmoregulation and membrane stabilization; anecdotal benefits in muscle symptoms. PMC

5. Alpha-lipoic acid – 100–300 mg/day. Antioxidant cofactor that may reduce oxidative stress. PMC

6. Creatine monohydrate – 2–5 g/day. Phosphocreatine buffer may aid short-burst muscle work; watch GI upset. PMC

7. Omega-3 fatty acids (EPA/DHA) – 1–2 g/day combined. Anti-inflammatory and potential LV remodeling adjunct; monitor with anticoagulants. JACC

8. Vitamin D – dose to reach sufficiency by labs. Bone/muscle support; deficiency is common in chronic illness. JACC

9. Magnesium – individualized dosing. Supports rhythm stability and muscle function; avoid excess with renal issues. JACC

10. Selenium – 50–100 mcg/day. Cofactor for antioxidant enzymes; only if deficient. JACC

Caution on L-carnitine: Once used empirically in BTHS, but practices vary given biochemical complexity; always ask your specialist before starting. PMC

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Immunity-booster / regenerative / stem-cell–type” medicines

1. Filgrastim (G-CSF, NEUPOGEN) – raises ANC during neutropenia to curb infections; used under hematology protocols (approved for other indications; off-label in BTHS). FDA Access Data

2. Pegfilgrastim (NEULASTA) – long-acting G-CSF with less frequent dosing; specialist-directed use (approved for other indications). FDA Access Data

3. Elamipretide (FORZINITY) – now FDA-approved for Barth syndrome to improve muscle strength; mitochondria-targeted, not a stem-cell therapy but regenerative-adjacent via mitochondrial support. U.S. Food and Drug Administration

4. AAV-TAZ gene replacement (investigational) – preclinical/early studies show reversal of cardiac and mitochondrial defects in BTHS models; clinical translation is under exploration. PMC+1

5. Clinical-trial mitochondrial modulators (investigational) – agents that aim to stabilize cardiolipin or improve electron transport beyond elamipretide remain under study. Discuss trial eligibility with your team. Stealth BioTherapeutics Inc.

6. Hematopoietic stem-cell transplant (HSCT) – not standard for BTHS and generally not recommended for isolated neutropenia; risk–benefit is unfavorable outside research/exceptional contexts. Decisions are specialist-only. PMC

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Surgeries/procedures

1. Heart transplant – For end-stage heart failure or life-threatening arrhythmias unresponsive to maximal therapy. Restores cardiac function when myocardium is irreversibly failing. PMC

2. Left-ventricular assist device (LVAD) – Mechanical pump used as a bridge to transplant or, rarely, destination therapy in adolescents/adults. Unloads the failing ventricle to improve circulation. PMC

3. ICD/CRT-D implantation – Treats or prevents dangerous ventricular arrhythmias; CRT can resynchronize ventricles in select dyssynchrony. Reduces sudden death risk and may improve HF symptoms. PMC

4. Gastrostomy tube – For children or adults who cannot meet calorie/protein needs or have severe fatigue with feeding; ensures reliable nutrition and growth. rarediseases.info.nih.gov

5. Electrophysiology procedures (ablation, device revisions) – Address specific arrhythmia substrates or optimize device therapy when indicated. PMC

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Preventions

1. Keep vaccines current per clinician guidance (flu, pneumococcal, and routine series). rarediseases.info.nih.gov

2. Rapid care for fever ≥38.0 °C, breathing trouble, chest pain, or sudden swelling. Barth Syndrome Foundation

3. Hand hygiene; avoid sick contacts and crowded indoor spaces during outbreaks. rarediseases.info.nih.gov

4. Daily weights/symptom logs to catch fluid retention early. JACC

5. Limit dietary salt if your cardiologist advises; avoid high-sodium processed foods. JACC

6. Maintain dental care to reduce bacteremia risk in neutropenia. rarediseases.info.nih.gov

7. Plan rest breaks during school/work/exercise to prevent overexertion. PMC

8. Heat avoidance and hydration in hot weather; cool indoor environments when symptomatic. PMC

9. Avoid unnecessary central venous lines; if needed, follow strict care bundles. rarediseases.info.nih.gov

10. Discuss travel plans with your team (med lists, vaccines, emergency letters). Barth Syndrome Foundation

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When to see a doctor urgently

Seek care now for fever, shaking chills, any breathing difficulty, chest pain, fainting, new palpitations, severe fatigue, fast weight gain/swelling, poor feeding or lethargy in infants, or if your home oximeter shows low oxygen. Any sudden decline in exercise capacity or new dizziness on standing also warrants prompt review. These signs may mean infection during neutropenia, fluid overload, arrhythmia, or low cardiac output—conditions that need timely treatment. Barth Syndrome Foundation+1

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What to eat and what to avoid

1. Prioritize: lean proteins (fish, poultry, eggs, legumes) to support muscle. Avoid: heavily processed meats high in sodium. JACC

2. Prioritize: fruits/vegetables for micronutrients. Avoid: very salty canned/packaged options unless rinsed/low-sodium. JACC

3. Prioritize: whole grains for steady energy. Avoid: excessive added sugars that cause energy dips. JACC

4. Prioritize: adequate fluids per cardiology advice. Avoid: energy drinks and high-caffeine stimulants that can trigger tachycardia. JACC

5. Prioritize: healthy fats (olive oil, nuts, omega-3 fish). Avoid: very high-sodium snacks (chips, instant noodles). JACC

6. Consider: vitamin D and other supplements only after labs and clinician approval. Avoid: high-dose “mitochondrial cocktails” without oversight. PMC

7. For infants/children: dietitian-guided calorie densification if growth lags. Avoid: unplanned restrictive diets. rarediseases.info.nih.gov

8. If fluid-restricted: learn label reading and portioning to control salt and fluids. JACC

9. GI upset days: small, frequent meals; low-fat, bland foods. Avoid: greasy or very spicy meals that worsen nausea. JACC

10. Coordinate supplements with meds: some (e.g., magnesium, fiber) can affect drug absorption. JACC

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 FAQs

1) Is Barth syndrome curable?
There’s no cure yet, but modern heart-failure therapy, infection prevention, and now elamipretide can markedly improve function and outcomes. Research on AAV-TAZ gene therapy is promising in models. U.S. Food and Drug Administration+1

2) What is the newest approved treatment?
In September 2025, the FDA granted accelerated approval to Forzinity (elamipretide) to improve muscle strength in eligible patients with Barth syndrome (≥30 kg). Post-marketing trials must confirm benefit. U.S. Food and Drug Administration+1

3) Why do infections hit so hard?
BTHS often causes neutropenia, lowering the body’s first-line defense against bacteria; rapid evaluation and sometimes G-CSF support are key. rarediseases.info.nih.gov+1

4) Why am I so easily fatigued?
Defective cardiolipin disrupts mitochondrial energy production, limiting ATP in heart and skeletal muscle. Pacing and supervised exercise help. PMC

5) What heart problems occur?
Dilated cardiomyopathy, left-ventricular non-compaction, arrhythmias, and heart failure can occur and need regular cardiology follow-up. MDPI+1

6) Are standard heart-failure drugs used?
Yes—ACE inhibitors/ARBs/ARNI, β-blockers, MRAs, diuretics, ± ivabradine, ± SGLT2 inhibitors—individualized by the HF team. Only elamipretide is BTHS-specific. FDA Access Data+2FDA Access Data+2

7) Do supplements help?
Some patients try CoQ10, riboflavin, creatine, etc., but evidence is limited; always coordinate with your clinician. PMC

8) Is carnitine recommended?
Use is controversial in BTHS; discuss risks/benefits with your specialist instead of self-starting. PMC

9) When is a defibrillator or CRT needed?
When arrhythmia risk or dyssynchrony is significant by guideline-based criteria; your electrophysiologist will assess. PMC

10) Can children play sports?
With tailored plans and supervision, light-to-moderate activity is often encouraged; avoid extremes and stop with symptoms. PMC

11) Is transplantation ever used?
Yes, for end-stage HF not responsive to medical/device therapy; selection is specialized. PMC

12) How do we prepare for emergencies?
Carry an ER letter with diagnosis, medications, and action steps; seek immediate care for fever, breathing trouble, or rapid swelling. Barth Syndrome Foundation

13) Will growth catch up?
Growth can improve with optimized nutrition and heart/infection control; endocrine review is sometimes needed. rarediseases.info.nih.gov

14) What about gene therapy now?
AAV9-TAZ replacement shows strong benefits in animal models; human trials are under development but not yet routine care. PMC+1

15) Where can we learn more and connect?
The Barth Syndrome Foundation offers care tools and updates; NIH GARD and GeneReviews provide clinical overviews for families and clinicians. Barth Syndrome Foundation+2rarediseases.info.nih.gov+2

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: October 18, 2025.

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