Barth syndrome: A life-threatening disorder caused by abnormal cardiolipin remodeling

Barth syndrome (BTHS) is a rare X-linked genetic disorder characterized by cardiomyopathy, skeletal myopathy, neutropenia, and organic aciduria. The presence and severity of clinical manifestations are highly variable in BTHS, even among patients with identical gene mutations. Currently, less than 200 patients are diagnosed worldwide, but it is estimated that the disorder may be substantially under-diagnosed due to the variable spectrum of clinical manifestations. BTHS is caused by mutations in the gene tafazzin (TAZ), resulting in defective remodeling of cardiolipin (CL), the signature phospholipid of the mitochondrial membranes. Many of the clinical sequela associated with BTHS can be directly attributed to mitochondria defects. In 2008, a definitive biochemical test was described based on detection of the abnormal CL profile characteristic of BTHS. This mini-review provides an overview of the etiology of BTHS, as well as a description of common clinical phenotypes associated with the disorder.