Adult-onset spinal muscular atrophy with SMN deletion and ultrastructural tubulo-filamentous inclusions identical to inclusion body myositis

Abstract

Sporadic inclusion body myositis (IBM) is an inflammatory myopathy with the diagnostic criteria on electron microscopy of rimmed vacuoles and 15–18 nm intracytoplasmic/intranuclear tubulofilamentous inclusions. There is a spectrum of neuromuscular diseases with these features and to our knowledge, this is the first case of a genetically proven adult-onset spinal muscular atrophy illustrating inflammation, rimmed vacuoles and tubulofilamentous inclusions. A 53-year-old male presented at 35 years with slowly progressive weakness, unsteady gait and atrophy of thighs and buttocks. His upper limbs and distal legs were unaffected. Sensory examination was normal. There was no dysphagia, ocular disturbance, sphincteric involvement and no family history of a neuromuscular disorder. Serum CK was normal. The EMG and deltoid muscle biopsy showed a neurogenic process. Subsequent quadriceps muscle biopsy histology demonstrated denervation and focal myonecrosis, rimmed vacuoles and sarcoplasmic inclusions. Ultrastructurally, rimmed vacuoles with myelinoid phospholipid whorls and degenerate organelles, intracytoplasmic and intranuclear 16 nm tubular filaments were present. Single strand conformational polymorphism (SSCP) showed homozygous deletions of exons 7 and 8 of the SMN1 gene on chromosome 5q. Our case of genetically proven adult-onset SMA confirms that rimmed vacuoles and 16 nm. IBM-like tubulofilamentous inclusions occur in a primary denervating condition. 1.Dubowitz V, Sewry C, Oldfors A. Muscle Biopsy: A Practical Approach. 5th ed. London: Elsevier, 2021.2.Semino-Mora C, Dalakas MC. Rimmed vacuoles with beta-amyloid and ubiquinated filamentous deposits in the muscles of patients with long-standing denervation (postpoliomyelitis muscular atrophy): similarities with inclusion body myositis. Hum Pathol 1998; 29: 1128–33.