Barth Syndrome Management Gets a Boost With Targeted Elamipretide Therapy

Barth syndrome is a rare but serious X-linked mitochondrial disease caused by hemizygous pathogenic variants in the TAFAZZIN gene, which encodes an enzyme critical for cardiolipin remodeling in mitochondrial membranes. Affecting almost exclusively males, the condition creates profound challenges across multiple organ systems from early childhood onward.

The disorder is characterized by dilated or hypertrophic cardiomyopathy — nearly always present before age five — alongside cyclic or chronic neutropenia, proximal skeletal myopathy, and prepubertal growth delay followed by catch-up growth after puberty. Heart failure, arrhythmia, and sudden death represent the most serious risks, while recurrent bacterial infections from neutropenia add further burden.

Diagnosis is confirmed through identification of an elevated monolysocardiolipin-to-cardiolipin ratio or detection of a TAFAZZIN pathogenic variant via molecular genetic testing. A landmark update in this review is the formal inclusion of elamipretide — a mitochondria-targeting peptide — as an indicated therapy to improve muscle strength in affected individuals, marking a significant step toward mechanism-based treatment.

Management remains largely supportive, encompassing antiarrhythmic medications or implantable defibrillators, careful cardiac fluid management, granulocyte colony-stimulating factor for neutropenia, physical therapy for myopathy, and nutritional support. Surveillance includes at minimum annual electrocardiography, Holter monitoring, and echocardiography, with semiannual complete blood counts. Clinicians are advised to avoid prolonged fasting, succinylcholine, and rectal thermometers in neutropenic patients, and to be alert to malignant hyperthermia risk.

For families, genetic counseling is essential: carrier mothers have a 50% chance of transmitting the variant per pregnancy, and prenatal or preimplantation genetic testing is available. Early identification of at-risk male relatives is strongly recommended to enable prompt initiation of treatment and preventive strategies.