Clinical presentation and natural history of Barth Syndrome: An overview

Abstract

Barth Syndrome is a rare X‐linked disorder caused by pathogenic variants in the gene TAFAZZIN, which encodes for an enzyme involved in the remodeling of cardiolipin, a phospholipid primarily localized to the inner mitochondrial membrane. Barth Syndrome is characterized by cardiomyopathy, skeletal myopathy, neutropenia, and growth abnormalities, among other features. In this review, we will discuss the clinical presentation and natural history of Barth Syndrome, review key features of this disease, and introduce less common clinical associations. Recognition and understanding of the natural history of Barth Syndrome are important for ongoing patient management and developing endpoints for the demonstration of efficacy of new and emerging therapies.

Studying Lipid-Related Pathophysiology Using the Yeast Model

“…Cardiomyopathy BTHS and its clinical manifestations have been previously discussed in other reviews (Raja et al, 2017b;Ghosh et al, 2019;Taylor et al, 2021;Zegallai and Hatch, 2021). Cardiomyopathy is the major clinical manifestation of BTHS, and all identified patients have developed cardiomyopathy at some point in their lives.…”

Mitochondrial Membranes and Mitochondrial Genome: Interactions and Clinical Syndromes

“…Additional features include exercise intolerance, lactic acidosis, and growth delay [73]. Electron-microscopy findings include enlarged mitochondria and abnormal mitochondrial cristae [74]. In one report, mtDNA content in fibroblasts from an affected individual with a frameshift variant in TAFAZZIN showed significant decrease in mtDNA copy numbers compared to healthy controls, whereas the cell line with a missense variant did not show a similar decrease.…”

Myocardial disturbances of intermediary metabolism in Barth syndrome

“…Cardiomyopathy is the most common clinical feature and primary driver of disease outcomes in Barth syndrome (BTHS; Online Mendelian Inheritance in Man [OMIM] 302060 ), a rare X-linked mitochondrial disorder first described by Dr. Peter Barth and colleagues in 1983 ( 1 , 2 ). Despite the broad variability in clinical presentation, which can include features such as neutropenia, skeletal myopathy, exercise intolerance, 3-methylglutaconic aciduria, and pre-pubertal growth retardation, cardiomyopathy manifests in approximately 90% of males with BTHS ( 3 , 4 ).…”

“…However, the severity and specific cardiomyopathic phenotype can vary both between individuals and throughout disease progression, with no definitive genotype-phenotype correlations having yet been identified. Dilated cardiomyopathy is most common, however other forms including restrictive ( 5 ), hypertrophic, and hypertrophic-dilated cardiomyopathy have also been reported ( 2 , 6 ).…”