Reducing body myopathy

Joseph R Siebert PhD (Dr. Siebert of the University of Washington has no relevant financial relationships to disclose.)
Harvey B Sarnat MD FRCPC MS, editor. (Dr. Sarnat of the University of Calgary has no relevant financial relationships to disclose.)
Originally released November 21, 1996; last updated May 13, 2016; expires May 13, 2019

Overview

Reducing body myopathy, a rare condition with early infant to adult onset, is characterized by abnormal inclusions in muscle fibers that are highlighted by special stains. A protein, FHL1, has been identified in these inclusions by proteomic techniques, and mutations in the corresponding gene identified in both sporadic and familial cases. Although the pathophysiology remains poorly understood, inclusions may be involved in processing and assembling ribosomes. Thus, their activity seems to be related intimately to muscle mass and function and leads to progressive muscle weakness, with wasting, and, in some, death due to respiratory failure.

Key points

 

• Reducing body myopathy is rare and manifests as infant or adult-onset forms.

 

• The disorder may be chronic and benign, or progressive and fatal.

 

• Presentation can involve muscles of the upper or lower body, which may be affected in symmetric or asymmetric fashion.

 

• Cytoplasmic inclusions identified microscopically may represent processing defects of ribosomes.

 

• Cases may be sporadic; familial cases appear to be X-linked recessive (developing from mutations in FHL1) or autosomal dominant with variable penetrance.

 

• Death is most often from respiratory failure, although cardiomyopathies may contribute.

Historical note and terminology

Reducing body myopathy is a rare disease of skeletal muscle, often classified as a congenital myopathy, although onset is more likely in early infancy (Dubowitz 1978) and adult onset is recognized. This condition was first described by Brooke and Neville in 2 unrelated children in whom muscle biopsy showed unusual structures that were termed "reducing bodies" (Brooke and Neville 1972). Over 25 cases have been reported in the medical literature, and the clinical presentation is variable.

Reducing bodies are defined by distinctive histochemical and ultrastructural abnormalities. Histologically, reducing bodies contain a substance that can reduce dihydroxydinaphthyl disulfide, confirming that sulfhydryl groups are present. They also stain black with menadione-linked alpha-glycerophosphate dehydrogenase and are able to reduce nitroblue tetrazolium even in the absence of the substrate alpha-glycerophosphate, giving the same intensive stain. By electron microscopy, reducing bodies appear as dense osmiophilic material that, at higher magnification, consists of closely packed variably and irregularly shaped particles mixed with fibrillar material, measuring 12 nm to 18 nm in width. Proliferation of cytoplasmic bodies and rimmed vacuoles is recognized. In reducing body myopathy, cytoplasmic bodies (CBs) may localize to peripheral, subsarcolemmal regions, giving an appearance termed “necklace cytoplasmic bodies” (Uruha et al 2015).

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