[Recurrent rhabdomyolysis and deficiency of carnitine palmityl transferase. Evidence of the responsibility of a mutant in 2 brothers]

Abstract

In two brothers who had been presenting since childhood with intermittent muscular attacks and myoglobinuria after sustained efforts, muscle carnitine palmityl transferase (CPT) activity was undetectable by the backward hydroxamate colorimetric method. Such a total deficiency could not easily fit in with the clinical features (normal muscular activity outside sustained efforts), with the normal results obtained at electromyography and with the moderate fatty overload detected at muscle biopsy. In order to elucidate these apparently discordant findings, another CPT measurement method, the forward optimized isotopic technique, was used. With this method, the catalytic activity of CPT can be measured, and enzyme inhibition by its substrate and the product of the reaction (palmityl CoA and palmitylcarnitine respectively) can be studied. The results showed that the catalytic activity of CPT was preserved in both patients, but the enzyme was abnormally sensitive to inhibitors. These 2 cases tend to demonstrate the existence of a mutant carnitine palmityl transferase.