Barth syndrome is an X-linked cardiac and skeletal mitochondrial myopathy. Barth syndrome may be due to lipid alterations because the product of the mutated gene is homologous to phospholipid acyltransferases. Here we document that a single mitochondrial phospholipid species, tetralinoleoyl-cardiolipin, was lacking in the skeletal muscle (n = 2), right ventricle (n = 2), left ventricle (n = 2), and platelets (n = 6) of 8 children with Barth syndrome. Tetralinoleoyl-cardiolipin is specifically enriched in normal skeletal muscle and the normal heart. These findings support the notion that Barth syndrome is caused by alterations of mitochondrial lipids.

Background Some Coronavirus disease 2019 (COVID-19) patients who have recovered from their acute infection after experiencing only mild symptoms continue to exhibit persistent exertional limitation that is often unexplained by conventional investigative studies. Research question What is the patho-physiological mechanism of exercise intolerance that underlies the post-COVID-19 long haul syndrome following COVID-19 in patients without cardio-pulmonary disease? Study Design and Methods This study examined the systemic and pulmonary hemodynamics, ventilation, and gas exchange in 10 post-COVID-19 patients without cardio-pulmonary disease during invasive cardiopulmonary exercise testing (iCPET) and compared the results to 10 age- and sex matched controls. These data were then used to define potential reasons for exertional limitation in the post-COVID-19 cohort. Results Post-COVID-19 patients exhibited markedly reduced peak exercise aerobic capacity (VO 2 ) compared to controls (70±11%predicted vs. 131±45%predicted; p<0.0001). This reduction in peak VO 2 was associated with impaired systemic oxygen extraction (i.e., narrow CaVO 2 /CaO 2 ) compared to controls (0.49±0.1 vs. 0.78±0.1, p<0.0001) despite a preserved peak cardiac index (7.8±3.1 vs. 8.4±2.3 L/min, p>0.05). Additionally, post-COVID-19 patients demonstrated greater ventilatory inefficiency (i.e., abnormal VE/VCO 2 slope: 35±5 vs. 27±5, p=0.01) compared to controls without an increase in dead space ventilation. Interpretation Post-COVID-19 patients without cardiopulmonary disease demonstrate a marked reduction in peak VO 2 from a peripheral rather than a central cardiac limit along with an exaggerated hyper-ventilatory response during exercise.