Long-term follow-up of bezafibrate treatment in patients with the myopathic form of carnitine palmitoyltransferase 2 deficiency.
Carnitine palmitoyltransferase 2 (CPT2) deficiency is a rare mitochondrial fatty acid oxidation (FAO) disorder characterized by myalgia, exercise intolerance, and rhabdomyolysis. We evaluate the efficacy of bezafibrate (BZ), a hypolipidemic drug, as a treatment for this form of CPT2 deficiency. A pilot trial was conducted with BZ in six patients for 6 months. There was a follow-up period of 3 years. The oxidation rates of the long-chain fatty acid derivative palmitoyl-CoA, measured in the mitochondria of the patients' muscles, were markedly lower than normal before treatment and increased significantly (+39 to +206%; P = 0.028) in all patients after BZ treatment. The evaluation of the therapeutic effects by the patients themselves (using the Short Form Health Survey (SF-36)), as well as by the physicians, indicated an improvement in the condition of the patients; there was an increase in physical activity and a decline in muscular pain. The results suggest that BZ has a therapeutic effect in the muscular form of CPT2 deficiency.
Bonnefont
J P
JP
INSERM U 781, Université Paris Descartes, Necker-Enfants Malades Hospital, Paris, France.
Bastin
J
J
Laforêt
P
P
Aubey
F
F
Mogenet
A
A
Romano
S
S
Ricquier
D
D
Gobin-Limballe
S
S
Vassault
A
A
Behin
A
A
Eymard
B
B
Bresson
J L
JL
Djouadi
F
F
D000203:Activities of Daily Living; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D001629:Bezafibrate / Q000627:therapeutic use*; D002334:Carnitine O-Palmitoyltransferase / Q000096:biosynthesis* / Q000172:deficiency* / Q000235:genetics; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000201:enzymology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D009135:Muscular Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000235:genetics; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D010146:Pain / Q000453:epidemiology / Q000209:etiology; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D010865:Pilot Projects; D012206:Rhabdomyolysis / Q000188:drug therapy / Q000201:enzymology; D016896:Treatment Outcome; D055815:Young Adult
D000960:Hypolipidemic Agents; D010171:Palmitoyl Coenzyme A; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002334:Carnitine O-Palmitoyltransferase; D001629:Bezafibrate