Barth syndrome

Abstract

Barth syndrome (BTHS) is an X-linked recessive disorder that is typically characterized by cardiomyopathy (CMP), skeletal myopathy, growth retardation, neutropenia, and increased urinary levels of 3-methylglutaconic acid (3-MGCA). There may be a wide variability of phenotypes amongst BTHS patients with some exhibiting some or all of these findings. BTHS was first described as a disease of the mitochondria resulting in neutropenia as well as skeletal and cardiac myopathies. Over the past few years, a greater understanding of BTHS has developed related to the underlying genetic mechanisms responsible for the disease. Mutations in the TAZ gene on chromosome Xq28, also known as G4.5, are responsible for the BTHS phenotype resulting in a loss-of-function in the protein product tafazzin. Clinical management of BTHS has also seen improvement. Patients with neutropenia are susceptible to life-threatening bacterial infections with sepsis being a significant concern for possible morbidity and mortality. Increasingly, BTHS patients are suffering from heart failure secondary to their CMP. Left ventricular noncompaction (LVNC) and dilated CMP are the most common cardiac phenotypes reported and can lead to symptoms of heart failure as well as ventricular arrhythmias. Expanded treatment options for end-stage myocardial dysfunction now offer an opportunity to change the natural history for these patients. Herein, we will provide a current review of the genetic and molecular basis of BTHS, the clinical features and management of BTHS, and potential future directions for therapeutic strategies. © 2013 Wiley Periodicals, Inc.

Mitophagy in hematopoietic stem cells

“…135 Patients with Barth syndrome have skeletal and cardiac myopathy and cyclic neutropenia, with heart failure and opportunistic infection being major causes of mortality.…”

Cardiovascular abnormalities in primary immunodeficiency diseases

“…Organic aciduria and hypocholesterolemia may also be present. The phenotype varies in severity among patients and may change over time (Schlame and Ren 2006;Jefferies 2013).…”

“…Less common manifestations include hypertrophic cardiomyopathy, left ventricular noncompaction, endocardial fibroelastosis, ventricular arrhythmias, and thromboembolic cerebrovascular events (Jefferies 2013).…”

The Mitochondrial Quality Control Protein Yme1 Is Necessary to Prevent Defective Mitophagy in a Yeast Model of Barth Syndrome

“…If Barth syndrome goes undiagnosed, sudden cardiac arrest due to ventricular arrhythmia or bacterial septicemia due to neutropenia leads to fatality for most infants within the first few years of birth. Although there is no known cure, the disease can be managed with standard heart failure medications or ventricular assist devices to prevent arrhythmia and with prophylactic antibiotic treatment and granulocyte colony-stimulating factor to treat recurrent infections (1,2). Despite symptom management that has extended the life span for most Barth syndrome patients, quality of life and life span are still not near the norm.…”

“…The understanding of the molecular basis of Barth syndrome was increased substantially when it was determined that the protein encoded by the TAZ gene, referred to as tafazzin, is a monolysocardiolipin (MLCL) 2 transacylase that transfers unsaturated fatty acyl chains from phosphatidylcholine or phosphatidylethanolamine to MLCL to produce cardiolipin (CL) ( Fig. 1) (3,4).…”