cqvip:Patients with the myopathic form of carnitine palmitoyltransferase II (CPT II ) deficiency typically experience muscle pain, cramps, and myoglobinuria during prolonged exercise. It has been suggested that carriers of CPT2 gene mutations a lso may have milder clinical symptoms, but fatty acid oxidation (FAO) has never been investigated in vivo in this group. We studied fuel utilization by indirect calorimetry and stable isotope methodology in four patients with CPT II deficie ncy, three subjects who carried one CPT2 gene mutation, and five healthy control subjects. Cycle exercise at a constant workload of 50% of maximal oxygen upta ke capacity was used to facilitate FAO. We found that in vivo oxidation of long chain fatty acids was normal at rest but severely impaired during prolonged, lowintensity exercise in patients with CPT II deficiency, and that two of the single CPT2 gene mutation carriers, who displayed symptom s of CPT II deficiency, had an FAO comparable with the patients. These results i ndicate that residual CPT II activity is sufficient to maintain long chain FAO at rest in CPT II deficiency but not to increase FAO during exercise. The findi ngs also suggest that single CPT2 gene mutations may exert a dominant negative effect on the tetrameric CPT II protein.
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