Cardiac Transplantation Does Not Improve Exercise Tolerance, Muscle Mass, or Substrate Metabolism in Barth Syndrome

Area of Science:

• Biochemistry
• Genetics
• Cardiology

Background:

• Barth syndrome (BTHS) is a rare X-linked disorder caused by TAFAZZIN gene mutations.
• It leads to mitochondrial dysfunction, cardioskeletal myopathy, and exercise intolerance.
• Cardiac transplantation is a treatment, but its metabolic effects in BTHS are unclear.

Purpose of the Study:

• Compare skeletal muscle morphology, metabolism, energetics, and exercise tolerance in BTHS patients with and without cardiac transplantation (BTHS-T vs. BTHS-noT) against healthy controls.
• Investigate the long-term metabolic consequences of BTHS and the impact of cardiac transplantation.

Main Methods:

• Compared 6 BTHS-T participants with 29 BTHS-noT and 28 healthy controls.
• Utilized graded exercise testing, echocardiography, body composition analysis, and 31P-MRS for mitochondrial energetics assessment.

Main Results:

• No significant difference in fat-free mass between BTHS-T and BTHS-noT.
• Both BTHS groups showed lower exercise capacity (V̇O2peak) and higher plasma lactate than controls.
• Skeletal muscle energetics revealed slower phosphocreatine recovery and reduced ATP production in BTHS patients, irrespective of transplantation.

Conclusions:

• Cardiac transplantation in BTHS may improve cardiac function but does not normalize skeletal muscle function, energetics, or exercise intolerance.
• The study highlights limitations of cardiac transplantation in fully addressing BTHS metabolic dysfunctions.
• Further research is needed for targeted therapies to improve metabolic abnormalities in BTHS.