LATE-ONSET MITOCHONDRIAL NEUROMYOPATHY - AN AGE-RELATED PHENOMENON

Peripheral neuropathy has been described in a number of cases of mitoc hondrial diseases. in these patients the onset of neuropathy varies fr om childhood to adulthood, whereas late onset is quite rare. We report here three males, ranging from 71 to 75 years with onset of periphera l neuropathy between 64 and 74 years of age. They complain of ataxic g ait, muscle aches, weakness and mild muscle atrophy, sensory impairmen t with predominant glove and stocking distribution, reduced or absent deep tendon reflexes. Neurophysiological examinations and sural nerve biopsy studies showed a sensorimotor neuropathy with axonal degenerati on in two cases and demyelination in one. Peroneus brevis muscle biops y revealed, apart from frank neurogenic changes, presence of ragged-re d fibers and cytochrome c oxidase negative fibers. Electron microscopy confirmed an abnormally increased presence of subsarcolemmal and inte rmyofibrillar mitochondria in muscle samples. These morphological feat ures suggested a mitochondrial disease that was confirmed by biochemic al investigations on muscle homogenate showing that the mitochondrial respiratory chain (MRC) enzyme activities were all reduced when compar ed to citrate synthase activity. In addition the presence of a partial ly inactive cytochrome c oxidase protein by ELISA was demonstrated in two cases. According to a recent ''mitochondrial theory of aging'' we think that a progressive decline of MRC function has affected either s keletal muscle or peripheral nerves in our patients. Being energy-requ iring processes, muscle metabolism as well as active axonal transport may become progressively defective with age resulting in a late-onset neuropathy.