Barth syndrome: cardiolipin, cellular pathophysiology, management, and novel therapeutic targets.
Barth syndrome is a rare X-linked genetic disease classically characterized by cardiomyopathy, skeletal myopathy, growth retardation, neutropenia, and 3-methylglutaconic aciduria. It is caused by mutations in the tafazzin gene localized to chromosome Xq28.12. Mutations in tafazzin may result in alterations in the level and molecular composition of the mitochondrial phospholipid cardiolipin and result in large elevations in the lysophospholipid monolysocardiolipin. The increased monolysocardiolipin:cardiolipin ratio in blood is diagnostic for the disease, and it leads to disruption in mitochondrial bioenergetics. In this review, we discuss cardiolipin structure, synthesis, and function and provide an overview of the clinical and cellular pathophysiology of Barth Syndrome. We highlight known pharmacological management for treatment of the major pathological features associated with the disease. In addition, we discuss non-pharmacological management. Finally, we highlight the most recent promising therapeutic options for this rare mitochondrial disease including lipid replacement therapy, peroxisome proliferator-activated receptor agonists, tafazzin gene replacement therapy, induced pluripotent stem cells, mitochondria-targeted antioxidants and peptides, and the polyphenolic compound resveratrol.
['Zegallai|Hana M|HM|', 'Hatch|Grant M|GM|http://orcid.org/0000-0002-1568-6071']
D000217:Acyltransferases D000818:Animals D000975:Antioxidants D056889:Barth Syndrome D002308:Cardiolipins D009202:Cardiomyopathies D002784:Cholesterol D003071:Cognition D057809:HEK293 Cells D006801:Humans D008246:Lysophospholipids D008928:Mitochondria D018482:Muscle, Skeletal D009135:Muscular Diseases D009154:Mutation D009206:Myocardium D009503:Neutropenia D010085:Oxidative Phosphorylation D010641:Phenotype D014157:Transcription Factors
Barth syndrome Cardiolipin Genetic disease Neutropenia Tafazzin Pharmacological management Resveratrol Cholesterol Heart Mitochondria Skeletal muscle