Barth syndrome (BTHS) is an X-linked recessive disorder that is typically characterized by
cardiomyopathy (
CMP), skeletal
myopathy, growth retardation,
neutropenia, and increased urinary levels of
3-methylglutaconic acid (3-MGCA). There may be a wide variability of phenotypes amongst BTHS patients with some exhibiting some or all of these findings. BTHS was first described as a disease of the mitochondria resulting in
neutropenia as well as skeletal and cardiac
myopathies. Over the past few years, a greater understanding of BTHS has developed related to the underlying genetic mechanisms responsible for the disease. Mutations in the TAZ gene on chromosome Xq28, also known as G4.5, are responsible for the BTHS phenotype resulting in a loss-of-function in the
protein product tafazzin. Clinical management of BTHS has also seen improvement. Patients with
neutropenia are susceptible to life-threatening
bacterial infections with
sepsis being a significant concern for possible morbidity and mortality. Increasingly, BTHS patients are suffering from
heart failure secondary to their
CMP. Left ventricular noncompaction (LVNC) and dilated
CMP are the most common cardiac phenotypes reported and can lead to symptoms of
heart failure as well as ventricular arrhythmias. Expanded treatment options for end-stage myocardial dysfunction now offer an opportunity to change the natural history for these patients. Herein, we will provide a current review of the genetic and molecular basis of BTHS, the clinical features and management of BTHS, and potential future directions for therapeutic strategies.