Objective
s: Barth Syndrome (BTHS) is an X-linked mutation in the TAZ gene characterized by cardiolipin deficiency, mitochondrial dysfunction and cardio-skeletal myopathy. We hypothe- sized that abnormal skeletal muscle oxygen (O
2
) utilization contributes to exercise intolerance in BTHS.
Methods
: Boys with BTHS (n=13) and healthy male controls (n=7) performed a graded exercise test on a cycle ergometer with continuous metabolic and EKG monitoring. Near infrared spectroscopy (NIRS), an indirect measure of tissue O
2
saturation and index of skeletal muscle O
2
utilization, was applied to the vastus lateralis during exercise. Cardiac function in BTHS was assessed by echocardiography and serum BNP to examine the relationship between resting cardiac function and exercise capacity in BTHS.
Results
: Age (16±5 vs 13±3 years; p=0.22), BMI (17±3 vs. 20±5; p=0.14) and BSA (1.0±0.5 vs 1.2±0.6 m
2
; p=0.3) were not different between BTHS and controls. BTHS had lower peak VO
2
(19±6 vs. 52±6 ml/kg/min, p < 0.001), lower % of predicted peak VO
2
(40±10% vs. 115±12%, p=0.0004), lower peak work rate (58±18 vs. 205±69 watts, p=0.0004), and lower peak O
2
pulse (4.6±1.6 vs. 14±6 ml O
2
/kg/beat, p< 0.00001) than controls. Peak HR in BTHS was lower but remained within normal peak predicted rate (172±14 vs. 197±11 bpm, p=0.001). Vastus lateralis tissue O
2
saturation at peak exercise decreased from baseline in controls as expected (-18±16%, p<0.001) but paradoxically increased from baseline in BTHS (+17±14%, p<0.03, p=0.0005 BTHS vs. controls) indicating impaired muscle O
2
utilization. Absolute (r= - 0.70, p<0.0001) and percent (r= - 0.70, p<0.001) change in NIRS from baseline was negatively associated with peak VO
2
. There was no correlation between peak VO
2
and resting EF (55±7%; r=0.12), SF (30±4%; r= -.26), myocardial performance index (0.4±0.1; r= -.3) or serum BNP (232±381; r=0.1).
Conclusion
: O
2
consumption during exercise in BTHS is severely reduced and caused, at least in part, by impaired skeletal muscle O
2
utilization. Resting cardiac function is not related to O
2
consumption in BTHS but cardiac dysfunction during exercise in BTHS is not excluded without further studies. Mitochondrial dysfunction likely mediates skeletal muscle O
2
utilization deficits during exercise in BTHS.
Extended recovery of cardiac function after severe infantile cardiomyopathy presentation of Barth syndrome
