title: Fuel utilization in subjects with carnitine palmitoyltransferase 2 gene mutations.
abstract: 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 also 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 deficiency, three subjects who carried one CPT2 gene mutation, and five healthy control subjects. Cycle exercise at a constant workload of 50% of maximal oxygen uptake 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, low-intensity exercise in patients with CPT II deficiency, and that two of the single CPT2 gene mutation carriers, who displayed symptoms of CPT II deficiency, had an FAO comparable with the patients. These results indicate 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 findings also suggest that single CPT2 gene mutations may exert a dominant-negative effect on the tetrameric CPT II protein.
authors.affiliation: Copenhagen Muscle Research Center, National University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. rh10679@rh.dk
authors.forename: Mette C
authors.initials: MC
authors.lastname: Ørngreen
authors.forename: Morten
authors.initials: M
authors.lastname: Dunø
authors.forename: Rasmus
authors.initials: R
authors.lastname: Ejstrup
authors.forename: Ernst
authors.initials: E
authors.lastname: Christensen
authors.forename: Marianne
authors.initials: M
authors.lastname: Schwartz
authors.forename: Massimo
authors.initials: M
authors.lastname: Sacchetti
authors.forename: John
authors.initials: J
authors.lastname: Vissing
mesh_terms: D000293:Adolescent; D000328:Adult; D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002151:Calorimetry / Q000379:methods; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000502:physiology*; D004252:DNA Mutational Analysis / Q000379:methods; D004734:Energy Metabolism / Q000502:physiology*; D005080:Exercise Test / Q000379:methods; D005227:Fatty Acids / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000235:genetics; D006728:Hormones / Q000097:blood; D006801:Humans; D007554:Isotopes / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*; D009154:Mutation; D010100:Oxygen / Q000097:blood; D012119:Respiration; D016526:Workload
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D006728:Hormones; D007554:Isotopes; D019344:Lactic Acid; D002334:Carnitine O-Palmitoyltransferase; D000409:Alanine; D010100:Oxygen