tafazzin

Tafazzin is a mitochondrial enzyme that remodels cardiolipin, a special phospholipid of the inner mitochondrial membrane. It is encoded by the TAZ gene on the X chromosome. Tafazzin functions as a phospholipid transacylase, participating in the deacylation/reacylation cycle that reshapes cardiolipin’s fatty acyl composition. By transferring fatty acid chains between phospholipids, tafazzin helps generate mature cardiolipin species, including tetralinoleoyl cardiolipin, which are important for mitochondrial membrane integrity, cristae structure, and optimal electron transport chain function.

Mutations in TAZ cause Barth syndrome, an X-linked recessive disorder. Tafazzin deficiency leads to abnormal cardiolipin remodeling, resulting in a characteristic pattern of cardiolipin and its precursor monolysocardiolipin that can be detected biochemically. The disorder manifests with cardiomyopathy, neutropenia, skeletal and systemic edema, growth delay, and episodic infections due to neutrophil dysfunction. Metabolic features can include elevated 3-mydroxy- and 3-memethylglutaconic acid excretion and lactic acidosis in some cases.

Diagnosis relies on suspicion from clinical features in males and confirmatory testing. Genetic testing identifies pathogenic variants in TAZ, and biochemical testing assesses the MLCL/CL ratio in blood or tissue samples. Management is supportive and multidisciplinary, addressing heart failure risk, infections, nutrition, and development. Treatments may include standard cardiomyopathy care and growth/immune support; G-CSF can be used for neutropenia. Research continues into targeted therapies, including approaches to correct cardiolipin remodeling.