Mallory body‐like inclusions in a hereditary congenital neuromuscular disease

Abstract

Subsequent to an earlier report on clinical and light microscopic data, peculiar Mallory body-like inclusions are described in muscle fibers of three genetically linked children. These Mallory body-like inclusions were unlike other well-defined intramuscular inclusions, such as nemaline, cytoplasmic, fingerprint, or sarcoplasmic bodies, but morphologically quite similar to hepatic Mallory bodies, because they were composed of three components: granular material and two types of filaments. Evidence is presented that these inclusions may contain desmin, the intermediate filament type characteristic of muscle. The exclusive appearance of these Mallory body-like inclusions in muscle biopsy specimens from three genetically related children of a large kinship emphasizes the uniqueness of these Mallory body-like inclusions in these muscle fibers as well as the special form of this congenital neuromuscular disorder.

Desmin‐related myopathy with mallory body–like inclusions is caused by mutations of the selenoprotein N gene

“…10 The genetic basis of the remaining forms of DRM were unknown, including the early-onset, autosomal recessive form with Mallory body-like inclusion bodies or hyaline/desmin plaques. 11 The "Mallory body-like" form of DRM (MB-DRM) was first described as "a form of congenital muscular dystrophy" (CMD) in five patients originat-ing from a genetic isolate in Northern Germany, 12,13 four of which were related by remote family links [MIM 253850]. Since then, approximately 14 additional cases have been reported.…”

“…7 Further morphological studies established that MB-DRM was defined by the presence, in approximately 10% of muscle fibers, of hyaline plaques devoid of any enzyme activity such as NADH, SDH, or ATPase, that corresponded at the ultrastructural level to peculiar intramyofibrillar inclusions. 13,14 These inclusions were composed of helical filaments, 10 to 12nm in diameter, arranged in bundles, and surrounded by irregular masses of electron-dense amorphous material. Finer filaments of 8 to 10nm in diameter frequently created a lighter perilesional halo.…”

“…13 Because the particular inclusions resembled the Mallory bodies of alcoholic liver disease, 15,16 they were termed MB-like inclusions. The finding that these deposits were immunoreactive for desmin, dystrophin, and ubiquitin 14 led eventually to the inclusion of this entity in the group of desminrelated myopathies.…”

Protein Aggregate Myopathies

“…Autophagic vacuoles, tubulofilamentous aggregates and paired helical filaments have occasionally been seen in DRM. [14,24,25] Similar morphological features and a variety of proteins have been identified in IBM also though not disease-specific mutant proteins. A further parallel may exist between genetic and nongenetic DRM as well as hereditary and sporadic, inflammatory IBM.…”

“…[11,12] Another DRM, recently further elucidated at the molecular level is Mallory body-like myopathy, [13,14] an autosomal-recessive childhood myopathy marked by scoliosis, muscle weakness and severe respiratory insufficiency which has now been found related to a homozygous mutation in the selenoprotein N1 (SEPN1) genes. [15] Whether, SEPN1 actually accumulates in these lesions is currently unknown because a respective antibody has not yet successfully been applied to these muscle specimens.…”