Barth syndrome

Barth syndrome (also known as 3-methylglutaconic aciduria type II, cardioskeletal myopathy with neutropenia and abnormal mitochondria, or BTHS) is a rare X-linked genetic disorder caused by mutations in the TAFAZZIN (TAFAZZIN/TAZ) gene located on chromosome Xq28. This gene encodes an enzyme essential for remodeling cardiolipin, a critical phospholipid in the inner mitochondrial membrane. Deficiency of functional tafazzin leads to abnormal cardiolipin composition, resulting in mitochondrial dysfunction that affects multiple organ systems. The hallmark features of Barth syndrome include dilated cardiomyopathy (often presenting in infancy), skeletal myopathy with muscle weakness and exercise intolerance, neutropenia (which may be chronic or cyclical and predisposes to recurrent bacterial infections), and growth delay. Affected individuals are almost exclusively male. Additional findings include 3-methylglutaconic aciduria (elevated urinary 3-methylglutaconic acid), fatigue, and feeding difficulties in early childhood. Cardiomyopathy can range from severe neonatal presentation with heart failure to milder forms detected later in childhood. Left ventricular noncompaction is also frequently observed. Some patients experience significant cardiac arrhythmias. There is currently no cure for Barth syndrome, and management is supportive and multidisciplinary. Treatment typically includes standard heart failure medications (ACE inhibitors, beta-blockers, diuretics) for cardiomyopathy, granulocyte colony-stimulating factor (G-CSF) for clinically significant neutropenia, physical therapy for muscle weakness, and nutritional support for growth delay. Cardiac transplantation may be considered in severe cases. Regular monitoring by cardiology, hematology, and metabolic specialists is essential. Research into gene therapy and other targeted approaches is ongoing. With improved recognition and management, survival and quality of life have improved significantly in recent decades.

Common questions about Barth syndrome