Researchers discovered that long-chain fatty acid oxidation and respiratory complex 1 deficiencies can differentiate Barth syndrome from idiopathic pediatric cardiomyopathy, as published in the Journal of Inherited Metabolic Disease. Barth syndrome and idiopathic pediatric cardiomyopathy are driven by metabolic defects such as long chain fatty acid oxidation disorder.

“[Barth syndrome] patients develop early onset cardiomyopathy and a derangement of intermediary metabolism consistent with mitochondrial disease, but the precise alterations in cardiac metabolism that distinguish [Barth syndrome] from idiopathic forms of cardiomyopathy are unknown,” Chatfield and colleagues explained.

The research team obtained 5 left ventricular heart tissue samples from patients with Barth syndrome and cardiomyopathy from the Barth Syndrome Foundation DNA and Tissue Bank. Three of these were from transplant surgeries and 2 were from organ donations after death.

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These samples were then compared with 4 explanted left ventricular tissue samples from patients with idiopathic dilated cardiomyopathy who were male and age-matched. Seven left ventricular tissue samples were obtained from healthy donor controls. 

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Chatfield and colleagues wanted to identify the metabolic derangements that differentiated Barth syndrome from idiopathic dilated cardiomyopathy in children.

“Results corroborate previous evidence for profound deficiencies in cardiolipin content and its linoleate enrichment as defining molecular features of [Barth syndrome], and reveal a pathologic accumulation of monolysocardiolipin to levels 5-fold greater than tetra-acyl cardiolipins in the heart,” they wrote.

Although the findings of the study are vast, the major accomplishment is that they found the differentiating metabolic defects distinguishing Barth syndrome for idiopathic dilated cardiomyopathy.

“In summary, results from this study corroborate accumulating evidence for defective [long-chain fatty acid] beta-oxidation as a central metabolic feature of [Barth syndrome] cardiomyopathy, and highlight the potential roles of complex I deficiency, [monolysocardiolipin] accumulation, and altered expression of [long-chain fatty acid] oxidation enzymes in this process,” they concluded.


Chatfield KC, Sparagna GC, Specht KS, et al. Long-chain fatty acid oxidation and respiratory complex I deficiencies distinguish Barth Syndrome from idiopathic pediatric cardiomyopathyJ Inherit Metab Dis. Published online November 25, 2021. doi:10.1002/jimd.12459. doi:10.1002/jimd.12459