Flexor-dominant myopathic phenotype in patients with His46Arg substitution in the Cu/Zn superoxide dismutase gene

We present the cases of 3 patients with a histidine-to-arginine substitution at position 46 of the Cu/Zn superoxide dismutase gene. Consistent with previous reports, the initial symptom in each patient was unilateral weakness in the distal leg muscles. Remarkably, muscular atrophy in these patients during the early stage of the disease was more specific to the flexor muscle group, with the extensor muscle group remaining intact over long-term observation. More interestingly, biopsy of the affected muscle in the early stage of the disease revealed necrotic and regenerative myofibers with infiltration of lymphocytes, resembling inflammatory myopathy. These novel findings might provide further insights into the pathophysiology of familial amyotrophic lateral sclerosis.