What is Barth syndrome?
A rare genetic disease of the mitochondria
Barth syndrome (BTHS) is a rare, life-threatening genetic disease caused by mutations in the TAFAZZIN gene on the X chromosome. Because of that X-linkage it almost exclusively affects males. Only a few hundred individuals are diagnosed worldwide, though the condition is believed to be underdiagnosed.
The TAFAZZIN gene encodes tafazzin, an enzyme that remodels cardiolipin — a lipid unique to the inner mitochondrial membrane that mitochondria need to produce energy efficiently. When tafazzin doesn't work, cells accumulate an immature form of the lipid (monolysocardiolipin) and mitochondrial energy production drops. The tissues that use the most energy — heart and skeletal muscle — are affected most.
How it presents
- Cardiomyopathy — weakening of the heart muscle, often dilated cardiomyopathy or left-ventricular non-compaction, frequently appearing in infancy. Heart failure and arrhythmia are the leading clinical concerns.
- Neutropenia — chronically or intermittently low neutrophil counts, raising the risk of serious bacterial infection.
- Skeletal myopathy and fatigue — muscle weakness and low exercise tolerance.
- Growth delay — slowed growth in childhood, often with a later catch-up phase, along with feeding difficulties in infancy.
- 3-methylglutaconic aciduria — elevated 3-methylglutaconic (3-MGC) acid in urine, a metabolic marker of the disease; Barth syndrome was historically classified as 3-methylglutaconic aciduria type II. Levels fluctuate and can be normal, so a normal urine result does not rule the disease out.
Severity varies widely between individuals, even within the same family.
How it's diagnosed
There are two routes to a diagnosis, and most patients end up needing both.
Genetic testing. Sequencing that covers the TAFAZZIN gene — a targeted test, a cardiomyopathy or neutropenia gene panel, or exome/genome sequencing — identifies the causal variant. Many diagnoses now start here, when a boy with unexplained cardiomyopathy or neutropenia is sequenced. No-cost sequencing programs exist — see iHope Genetic Health and free genetic testing for suspected mitochondrial disease. A confirmed variant also enables carrier testing for mothers and sisters and prenatal testing, since carriers have a 50% chance of passing the variant to each child.
The biochemical test. The monolysocardiolipin-to-cardiolipin (MLCL/CL) ratio, measurable from a dried blood spot, is elevated in Barth syndrome with near-complete sensitivity and specificity — including in atypical cases where individual cardiolipin species read normal. It confirms that a TAFAZZIN variant of uncertain significance is actually disease-causing, and it can establish the diagnosis when sequencing is negative or unavailable. Elevated urine 3-MGC can be an early clue that prompts testing, but because it fluctuates it is not reliable on its own.
Living with Barth syndrome
Care is multidisciplinary: cardiology (heart-failure management, and transplant in severe cases), immunology and hematology (including G-CSF for neutropenia), nutrition, and physical therapy. The first disease-specific therapy was approved in 2025 — see therapy progress for the current treatment landscape.
Frequently asked questions
What causes Barth syndrome?
Mutations in the TAFAZZIN gene on the X chromosome. The gene encodes tafazzin, an enzyme that remodels cardiolipin, a lipid the inner mitochondrial membrane needs for efficient energy production. Without working tafazzin, cells accumulate monolysocardiolipin and mitochondrial energy output drops.
How is Barth syndrome inherited?
It is X-linked. Mothers who carry a TAFAZZIN variant have a 50% chance of passing it to each child; sons who inherit it are affected, daughters who inherit it are carriers. It almost exclusively affects males.
How is it diagnosed?
Two routes: sequencing that covers the TAFAZZIN gene (targeted test, gene panel, or exome/genome), and the monolysocardiolipin-to-cardiolipin (MLCL/CL) ratio measured from a dried blood spot, which is elevated in Barth syndrome with near-complete sensitivity and specificity. Elevated urine 3-methylglutaconic acid can be an early clue but fluctuates.
Is there a treatment?
The first disease-specific therapy, FORZINITY (elamipretide), received FDA accelerated approval in September 2025 for patients weighing at least 30 kg. Care otherwise centers on managing the heart, infection risk from neutropenia, nutrition, and physical therapy. Several further therapies, including gene therapy, are in development.
How rare is it?
Only a few hundred individuals are diagnosed worldwide. The condition is believed to be underdiagnosed, partly because only two laboratories worldwide are known to offer the clinical MLCL/CL assay.
Where can families find support?
The Barth Syndrome Foundation (barthsyndrome.org) connects families, clinicians, and researchers, runs a registry and a biennial conference, and funds research.
Learn more
- Barth Syndrome Foundation ↗ — families, clinicians, and research
- BSF research programs ↗
- Funding index — grants open to BTHS researchers
Last updated August 28, 2026.