DETROIT — Barth Syndrome (BTHS) is a rare and serious genetic disorder that primarily affects males and is passed from mother to son; women who are carriers do not show symptoms of the disorder. Fifty percent of children born to a mother who is a carrier will inherit the defective gene, and all daughters born to an affected man will be carriers. BTHS is caused by a mutation in the tafazzin gene that results in decreased production of cardiolipin, an essential lipid for energy metabolism.

BTHS causes cardiomyopathy, a disorder of the heart muscle; neutropenia, a reduction in the number of white blood cells; hypotonia, reduced muscle tone; undeveloped skeletal muscles and muscle weakness; delayed growth; decreased stamina; physical disability; and methylglutaconic aciduria, an increase in an organic acid that is characteristic of abnormal mitochondrial function.

A team of researchers at Wayne State University has received funding from the Barth Syndrome Foundation to test a novel hypothesis that cardiolipin deficiency leads to disruption of the tricarboxylic acid (TCA) cycle, a series of enzyme-catalyzed chemical reactions that forms a key part of aerobic respiration in cells, leading to metabolic defects that have potential to be rescued by restoring TCA cycle deficiencies.

Led by Miriam L. Greenberg, Ph.D., professor of biological sciences in the College of Liberal Arts and Sciences and a resident of Ann Arbor, the team hopes to find ways to restore the TCA cycle metabolites that may offer potential new treatments for the disorder.

"Cardiolipin deficiency is implicated in a number of disorders such as diabetic cardiomyopathy, heart failure, ischemia/reperfusion injury and non-alcoholic fatty liver disease," said Greenberg. "Understanding the mechanisms underlying the involvement of cardiolipin in cellular functions may provide insight into these disorders and Barth Syndrome, and may help identify potential drug targets."

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