Barth Syndrome
A rare X-linked genetic disorder affecting cardiolipin production in mitochondrial membranes, causing cardiomyopathy, muscle weakness, and neutropenia. Elamipretide stabilises mitochondrial cardiolipin and received accelerated FDA approval for Barth syndrome, representing a novel mitochondria-targeted peptide therapy.
Technical Context
X-linked recessive (TAFAZZIN gene, Xq28): affects males almost exclusively. TAFAZZIN encodes a transacylase that remodels cardiolipin — the signature phospholipid of the inner mitochondrial membrane. Cardiolipin remodelling deficiency → abnormal cardiolipin species (monolysocardiolipin accumulation, reduced tetralinoleoyl-cardiolipin) → disorganised mitochondrial cristae → impaired electron transport chain complex assembly → reduced ATP production + increased ROS. Clinical features: dilated cardiomyopathy (often presenting in infancy — leading cause of morbidity/mortality), skeletal myopathy (exercise intolerance, proximal weakness), neutropenia (cyclic or intermittent — increasing infection risk), and growth delay. Elamipretide (Barth syndrome approval): mitochondria-targeted tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2) that binds cardiolipin → stabilises cristae structure → improves ETC complex organisation → enhanced ATP production and reduced ROS. TAZPOWER trial: improvements in functional assessments. FDA accelerated approval (2024) based on functional endpoints; confirmatory trials required.