Sporadic inclusion body myositis (IBM) is the most common age-related muscle disease in the elderly that results in severe disability. Although traditionally considered an inflammatory myopathy, it is now considered to be more consistent with a myodegenerative disease ... Sporadic inclusion body myositis (IBM) is the most common age-related muscle disease in the elderly that results in severe disability. Although traditionally considered an inflammatory myopathy, it is now considered to be more consistent with a myodegenerative disease (Sugarman et al., 2002; Askanas and Engel, 2006). See 600737 for a description of a presumably distinct disorder, inclusion body myopathy-2.
The vast majority of IBM occurs sporadically; however, rare familial occurrence has been reported. Inclusion body myositis is a slowly progressive inflammatory myopathy characterized clinically by weakness of the proximal parts of the limbs, diminished deep tendon reflexes, ... The vast majority of IBM occurs sporadically; however, rare familial occurrence has been reported. Inclusion body myositis is a slowly progressive inflammatory myopathy characterized clinically by weakness of the proximal parts of the limbs, diminished deep tendon reflexes, dysphagia, and mixed myopathic and neurogenic changes on electromyography. Baumbach et al. (1990) reported the first familial cases. Six persons in 2 generations were affected in an autosomal dominant pattern of inheritance. All 5 affected males had significant clinical findings with age of onset at 20 to 30 years. The only affected female was clinically asymptomatic but on muscle biopsy showed mild changes consistent with IBM. Garlepp et al. (1995) found particularly severe involvement of the quadriceps femoris muscles in the lower extremity and of the forearm flexor muscles in the upper limbs. - Pathologic Findings Garlepp et al. (1995) defined IBM histologically by the presence of characteristic rimmed vacuoles with immunohistochemical evidence of the beta-amyloid fragment of the beta-amyloid precursor protein (beta-APP; 104760) and ubiquitin (see UBB; 191339). Askanas et al. (2003) reported a 70-year-old African American man with sporadic IBM and cardiac amyloidosis associated with a mutation in the transthyretin gene (TTR; 176300.0009). Cultured skeletal muscle fibers from the patient showed vacuolar degeneration, congophilic inclusions, and clusters of colocalizing beta-amyloid and TTR immunoreactivities, none of which were found in normal cultured muscle fibers. Overexpression of the APP gene resulted in accelerated fiber degeneration, greater congophilic inclusions, and accumulation of heavy beta-amyloid oligomers. Askanas et al. (2003) suggested that the TTR mutation may have predisposed the patient to IBM by increasing beta-amyloid deposition in skeletal muscle. Fratta et al. (2004) found that 70 to 80% of the vacuolated muscle fibers in samples from 10 patients with sporadic inclusion body myositis contained strong immunoreactivity to mutant ubiquitin (UBB+1) in the form of numerous well-defined plaque-like, dotted, or elongated aggregates. Similar aggregates were identified in 10 to 15% of the nonvacuolated normal-appearing fibers. In the abnormal fibers, these aggregates were concurrently immunoreactive for wildtype UBB and either beta-amyloid or phosphorylated tau (MAPT; 157140). None of the control biopsies were immunoreactive to UBB+1. Fratta et al. (2004) suggested that the UBB+1-inhibited proteasome cannot properly degrade toxic proteins, resulting in their accumulation and aggregation.
Garlepp et al. (1995) found the frequency of the apolipoprotein E4 allele to be 0.29 in a group of 14 patients with IBM. This was considerably higher than that found in their control group of other inflammatory diseases ... Garlepp et al. (1995) found the frequency of the apolipoprotein E4 allele to be 0.29 in a group of 14 patients with IBM. This was considerably higher than that found in their control group of other inflammatory diseases (0.15) and the general population (0.13). Fifteen- to 18-nm tubulofilament inclusions similar to those found in IBM have been observed in some cases of oculopharyngeal dystrophy (164300), which is caused by short expansions of a GCG trinucleotide repeat in the gene encoding poly(A)-binding protein-2 (PABP2; 602279). However, Mezei et al. (1999) did not observe any expansions in PABP2 in 22 sporadic or 3 familial cases of IBM.