left ventricular noncompaction (LVNC). TAFAZZIN has also been associated with various cancers, including breast cancer, papillary thyroid carcinoma and non-small cell lung cancer, glioma, gastric cancer, thyroid neoplasms, and rectal cancer. Barth syndrome Barth syndrome (BTHS) is an X-linked disease caused by mutations in the TAFAZZIN gene. More than 160 mutations in the TAFAZZIN gene have been linked to this disease. It is a rare disease, found in 1 out of every 300,000 to 400,000 live births, though it is widely known that the disease is underdiagnosed. Although BTHS occurs almost exclusively in males, there has been one identified case of BTHS in a female patient. Tafazzin is responsible for remodeling of a phospholipid cardiolipin (CL), the signature lipid of the mitochondrial inner membrane. TAFAZZIN gene mutations that cause Barth syndrome result in the production of tafazzin proteins with little or no function. As a result, linoleic acid is not added to cardiolipin, which disrupts normal mitochondrial shape and function, including energy production and protein transport. Barth syndrome patients exhibit defects in cardiolipin metabolism, including aberrant cardiolipin fatty acyl composition, accumulation of monolysocardiolipin (MLCL), and reduced total cardiolipin levels. This may lead to acute metabolic decompensation and sudden death. Tissues with high energy demands, such as the heart and other muscles, are most susceptible to cell death due to reduced energy production in mitochondria and protein transport. Additionally, affected white blood cells have abnormally shaped mitochondria, which could impair their ability to grow (proliferate) and mature (differentiate), leading to a weakened immune system and recurrent infections. Dysfunctional mitochondria likely lead to other signs and symptoms of Barth syndrome. Phenotypes of Barth Syndrome encompass a wide range, with cardiovascular, musculoskeletal, neurological, metabolic, and hematologic consequences. Common clinical manifestations include: dilated cardiomyopathy (enlarged and weakened heart) muscle weakness recurrent infections short stature endocardial fibroelastosis growth retardation neutropenia organic aciduria (3-methylglutaconic acid) Additional features include hypertrophic cardiomyopathy, isolated noncompaction of left ventricular myocardium (INVM), ventricular arrhythmia, motor delay, poor appetite, fatigue and exercise intolerance, hypoglycemia, lactic acidosis, hyperammonemia, and dramatic late catch-up growth after growth delay throughout childhood. A c.348C>T mutation resulted in dilated cardiomyopathy with noncompaction of the ventricular myocardium. A patient with a frame shift mutation of c.227delC displayed symptoms of neutropenia, cardiomegaly, and other common symptoms of Barth Syndrome. Another c.C153G mutation resulted in severe metabolic acidosis, cardiomegaly, and other major symptoms of Barth syndrome. There is no known cure