Myopathic changes caused by protein aggregates in adult‐onset spinal muscular atrophy

Abstract

Spinal muscular atrophy (SMA), an autosomal‐recessive lower motor neuron disease, causes progressive proximal muscle waste and weakness. It remains unclear whether myopathic changes are involved in pathogenesis. We encountered a patient with adult‐onset SMA caused by a homozygous deletion in exon 7 of the survival motor neuron 1 (SMN1) gene who had had four copies of SMN2 exon 7. Muscle biopsy showed neurogenic features of groups of atrophic fibers, fiber‐type grouping, and pyknotic nuclear clumps associated with fibers with rimmed vacuoles. Immunohistochemistry revealed sarcoplasmic aggregates of phosphorylated TDP‐43 and p62 but not SMN. This study demonstrated myopathic changes with the accumulation of phosphorylated p62 and TDP‐43 in the muscles of a patient with SMA, suggesting that abnormal protein aggregation may be involved in myopathic pathology.