Clinical and neurophysiologic response of myopathy and neuropathy in long-chain l-3-hydroxyacyl-CoA dehydrogenase deficiency to oral prednisone

The purpose of this study was to evaluate the clinical and neurophysiologic responses to oral prednisone therapy in a boy with enzymatically confirmed long-chain l-3-hydroxyacyl-CoA dehydrogenase deficiency in biopsied muscle and cultured skin fibroblasts. This boy presented with progressive limb girdle myopathy, recurrent myoglobinuria, peripheral sensorimotor axonopathy, and intraventricular conduction delays. Prior to prednisone therapy, at age 8 years, he exhibited marked distal weakness greater than proximal weakness with a waddling and high-steppage gait, Gowers' maneuver (10 s to rise from the floor), fatigue after 3-20 yards of walking and the ability to climb only 2 stairs. Serum levels of creatine kinase rose from 34 to 4,124 U/L following mild exertion. Nerve conduction studies revealed progressive axonopathy with secondary demyelination. Four weeks after initiation of oral prednisone (0.75 mg/kg/day) therapy, there was approximately a 100% increase in power and endurance. He was able to walk at least 100 yards before tiring, could rise from sitting on the floor in 3-4 s, and was able to climb 20 steps in 30 s. There was concurrent improvement in nerve conduction studies. Prednisone was gradually withdrawn over the next 4 months to 0.19 mg/kg/day; lower doses of 0.08 mg/kg/day resulted in a marked deterioration in power to the prior state. Although 0.19 mg/kg/day did not maintain the peak power achieved at 0.75 mg/kg/day, it provided adequate baseline power and endurance. It is concluded that there was a significant clinical and neurophysiologic response to prednisone at a dosage ≥0.16 mg/kg/day. Prednisone may stabilize muscle and neuronal plasma membranes, as well as the fatty acid oxidation enzyme complex in the mitochondrial membrane.