Arginine kinetics are altered in a pilot sample of adolescents and young adults with Barth syndrome

Authors: CADE, TODD - Washington University; BOHNERT, KATHRYN - Washington University; BITTEL, ADAM - Washington University; CHACKO, SHAJI - Children'S Nutrition Research Center (CNRC); PATTERSON, BRUCE - Washington University; PACAK, CHRISTINA - University Of Florida; BYRNE, BARRY - University Of Florida; VERNON, HILARY - Johns Hopkins University School Of Medicine; REEDS, DOMINIC - Washington University

Submitted to: Molecular Genetics and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/29/2020
Publication Date: 11/4/2020
Citation: Cade, T.W., Bohnert, K.L., Bittel, A.J., Chacko, S.J., Patterson, B.W., Pacak, C.A., Byrne, B.J., Vernon, H.J., Reeds, D.N. 2020. Arginine kinetics are altered in a pilot sample of adolescents and young adults with Barth syndrome. Molecular Genetics and Metabolism. 25:100675. https://doi.org/10.1016/j.ymgmr.2020.100675.
DOI: https://doi.org/10.1016/j.ymgmr.2020.100675

Interpretive Summary: Barth syndrome is a rare condition that results in enlarged and weakened heart, weakness in muscles, low cholesterol level and metabolic disturbances. Although dysregulated cardiac and skeletal muscle, glucose and fatty acid metabolism have been reported, much less is known about amino acid metabolism in Barth condition. Arginine is an amino acid that helps the body build protein and low plasma arginine concentration has been reported in Barth condition. The objective of this study was to characterize arginine metabolism in adolescents and young adults with Barth syndrome. Scientists in Houston, Texas demonstrated that arginine rate of appearance was lower in adolescents and young adults with Barth condition compared to healthy controls. This study provides a foundation for future studies on how arginine and potentially other amino acid abnormalities contribute to the Barth condition in humans.

Technical Abstract: Barth syndrome (BTHS) is a rare, X-linked cardioskeletal myopathy caused by recessive mutations in the tafazzin (TAZ) gene resulting in metabolic disturbances including an increased monolysocardiolipin to cardiolipin ratio, 3-methyglutaconic aciduria, hypocholesterolemia. Although dysregulated cardiac and skeletal muscle glucose and fatty acid metabolism and energetics have been reported, much less in known about amino acid metabolism in BTHS. Low plasma arginine concentration in BTHS has received considerable clinical attention and a proportion of patients have been treated with oral L-arginine and L-citrulline amino acid supplementation. However, other features of arginine metabolism, including arginine kinetics, are not known in BTHS. Therefore, the objective of this pilot study was to characterize whole-body arginine kinetics in a pilot sample of adolescents and young adults with BTHS.