Barth syndrome (BTHS) is an X-linked, multisystem mitochondrial disease, also referred to as 3-Methylglutaconic Aciduria Type II, X-linked cardioskeletal myopathy and neutropenia, cardioskeletal myopathy with neutropenia and abnormal mitochondria, endocardial fibroelastosis type 2 (EFE2), TAFAZZIN Deficiency, or TAZ Deficiency [1, 2]. Because it is an X-linked disorder, Barth syndrome primarily affects males [1]. Barth syndrome is a rare disorder, with less than ten new patients estimated to be identified each year in the United States [3]. Miller et al., estimates one infant out of every one million live male births is born with Barth syndrome [though it is possible that the prevalence is higher [4]. Research from the Barth Syndrome Foundation has found that onset of symptoms most frequently occurs within the first year of life, with a high risk for fatality during infancy due to heart failure or infection. It’s estimated that 40% of Barth Syndrome cases prove to be fatal prior to the age of 5. With that being said, patients are generally living longer with earlier diagnosis, improved support, better disease management, with many patients living into adulthood [1, 2, 5].

Barth syndrome is an inborn error of lipid metabolism.  TAFAZZIN [6], originally named G4.5 [7], encodes a protein that catalyzes the final step in the remodeling of an essential phospholipid called cardiolipin, which plays both structural and functional roles in the inner mitochondrial membrane [6]. Pathogenic variants or mutations in the TAFAZZIN gene disrupt its function and prevent the synthesis of the mature version of cardiolipin. Instead, the cardiolipin precursor called monolysocardiolipin builds up, altering the mitochondrial membrane structure and metabolism, ultimately resulting in decreased energy production [6, 8]. Over 200 TAFAZZIN mutations have been identified [9].

The symptoms of Barth syndrome can be heterogeneous and vary from person to person, but commonly include [1, 9]:

• • • Cardiomyopathy, or heart disease, such as dilated cardiomyopathy (DCM), left ventricular noncompaction (LVNC), hypertrophic cardiomyopathy (HCM), and arrhythmias
    • Skeletal muscle myopathy or hypotonia, resulting in symptoms such as weakness, fatigue, exercise intolerance, and stiffness
    • Growth and developmental delay
    • Neutropenia, or decreased white blood cell levels, leading to increased susceptibility to infections
    • Gastrointestinal manifestations such as frequent vomiting and diarrhea
    • Increased excretion of 3-methylglutaconic acid (3-MGC) through the urine
    • Characteristic facial features during infancy

To determine if your loved one has Barth syndrome, their healthcare provider will evaluate their symptoms and may perform the following tests [1, 9]:

• • • Molecular genetic testing for TAFAZZIN variants
    • Measurement of monolysocardiolipin-to-cardiolipin ratio [10, 11], which is currently only available via Amsterdam UMC
    • Analysis of 3 -MGC in the urine or plasma

Like all mitochondrial diseases, there is currently no cure for Barth syndrome. However, patient survival and quality of life have increased with improved symptom management, including the following:

• • • FORZINITY™ (elamipretide), recently granted accelerated approval by the U.S. Food and Drug Administration (FDA), is prescribed to improve muscle strength in patients with genetically confirmed Barth syndrome weighing at least 30 kilograms (approximately 66 pounds) [1, 12]. This medication is currently only available in the United States.
    • Cardiac medication, devices, or transplantation to manage cardiomyopathy [1, 2, 9]
    • Granulocyte colony stimulating factor to increase white blood cell counts during neutropenia and antibiotics to reduce the risk of infection [1, 2, 9]
    • Physical therapy to improve muscle weakness [1]
    • Arginine supplementation to potentially increase growth rate [9]
    • Feeding therapy or gastrostomy tube placement for poor weight gain [1]
    • Cornstarch supplements before bedtime to prevent muscle loss overnight [1, 2]

Patients benefit from multidisciplinary supportive care [1].

UMDF is proud to partner with Barth Syndrome Foundation to support patients diagnosed with Barth syndrome.

If you have other forms of mitochondrial disease — or are still on your diagnostic journey and suspect mito, we encourage you to reach out to UMDF’s support team at (888) 900-6486 or support@umdf.org. 

• Get Support
  Connect with our Support & Education Team online, via email at support@umdf.org or phone at (888) 900-6486.

• Check our clinical trials finder
  Use our Clinical Trials Finder tool to see if you qualify for any clinical trials.

• Join our patient registry, mitoSHARE
  We are actively recruiting Barth syndrome families to participate in our patient registry, mitoSHARE. Patient registries like mitoSHARE are an integral part in charting a course toward treatments and cures for Barth syndrome and other mitochondrial diseases. There are currently over 30 active mitochondrial disease clinical trials. Next generation patient registries like mitoSHARE are an integral part of expanding that number.

• Become an advocate
  Ask your representatives to prioritize mitochondrial disease research and support via the UMDF Advocacy Center. We’ll send regular action items so you – and your friends and family – can let Congress know where we need their support. Click here to sign up.

• Join the conversation online
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• Get involved
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UMDF is helping chart a path toward treatments and eventual cure of mitochondrial diseases like Barth syndrome through:

• • • Research & Funding: UMDF has provided more than $18 million in research funding to find treatments for diseases like Barth. UMDF advocacy has helped secure an additional $80 million in federal funding via the Department of Defense and National Institutes of Health.
    • Data: Over two decades ago, UMDF pioneered patient registries for the mitochondrial disease community. Today, our next generation patient registry, mitoSHARE, is helping chart a path toward the treatment and eventual cure of mitochondrial diseases.
    • Patient Support: Thousands of families just like you depend upon UMDF for support and education on diseases like Barth syndrome. Attendance at our support meetings annually tops 5,000, including disease specific support meetings for families.
    • Clinician Support: To help educate clinicians on diseases like Barth syndrome, we feature monthly Bench to Bedside clinician seminars, host the annual Mitochondrial Medicine Symposium, support the Mitochondrial Care Network, and educate clinicians on our Mito U platform.
    • Advocacy: UMDF was proud to partner with the Barth Syndrome Foundation and other mito-related patient advocacy groups to help move the Barth-related treatment Forzinity (elamipretide) forward with the FDA, including multiple advocacy action campaigns, letters of support, publicity and more.

• • • • Barth Syndrome Foundation
      • National Organization for Rare Disorders: Barth Syndrome

UMDF is here to help. Contact the Support Line at (888) 900-6486 weekdays from 8:00am to 5:00pm EST to connect with our Patient Concierge. Or, via email contact  support@umdf.org.

1. Ferreira et al., 2014 (last updated 2026). Barth Syndrome.
2. Clarke et al., 2013. Barth syndrome.
3. Miller PC, Ren M, Schlame M, Toth MJ, Phoon CKL. A Bayesian Analysis to Determine the Prevalence of Barth Syndrome in the Pediatric Population. J Pediatr. 2020 Feb;217:139-144. doi: 10.1016/j.jpeds.2019.09.074. Epub 2019 Nov 12. PMID: 31732128.
4. Cantlay et al., 1999. Genetic analysis of the G4.5 gene in families with suspected Barth syndrome.
5. Mazar et al., 2019. Understanding the life experience of Barth syndrome from the perspective of adults: a qualitative one-on-one interview study.
6. Ikon & Ryan, 2019. Barth Syndrome: Connecting Cardiolipin to Cardiomyopathy.
7. Bione et al., 1996. A novel X-linked gene, 5 is responsible for Barth syndrome.
8. Vreken et al., 2000. Defective Remodeling of Cardiolipin and Phosphatidylglycerol in Barth Syndrome.
9. Jeffries, 2013. Barth syndrome; and Barth Syndrome Foundation, 2026.
10. Kulik et al., 2008. Bloodspot Assay Using HPLC-Tandem Mass Spectrometry for Detection of Barth Syndrome.
11. Houtkooper et al., 2009. Cardiolipin and monolysocardiolipin analysis in fibroblasts, lymphocytes, and tissues using high-performance liquid chromatography-mass spectrometry as a diagnostic test for Barth syndrome.
12. https://umdf.org/forzinity-elamipretide/