Distal myopathy with rimmed vacuoles and hereditary inclusion body myopathy

Abstract

Distal myopathy with rimmed vacuoles (DMRV) and hereditary inclusion body myopathy (hIBM) share similar clinical features, including onset in young adulthood with preferential involvement of the anterior compartment of the lower legs and sparing of the quadriceps femoris muscles. The most significant muscle pathology is the presence of rimmed vacuoles, which appear to play a major role in muscle atrophy and weakness. After the discovery of the gene locus in both DMRV and hIBM on chromosome 9 and mutations in the gene encoding the enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), it became clear that they are allelic disorders. From gene analysis, it is evident that these diseases are not restricted to people of Japanese and Jewish ancestry, but that they are widely distributed throughout all ethnic groups. Although defective glycosylation to a muscle fiber has been suggested, the mechanism by which myofibrillar degeneration is followed by rimmed vacuole formation remains to be clarified.

Peracetylated N-Acetylmannosamine, a Synthetic Sugar Molecule, Efficiently Rescues Muscle Phenotype and Biochemical Defects in Mouse Model of Sialic Acid-deficient Myopathy

“…Distal myopathy with rimmed vacuoles (DMRV) 3 /hereditary inclusion body myopathy (hIBM) is a gradually progressive autosomal recessive disorder that predominantly affects distal muscles at the initial stages but also involves proximal muscles during the progression of the disease (1,2). DMRV/hIBM has been reported as quadriceps-sparing myopathy because the quadriceps muscles are relatively spared even during the late stage of the disease (3).…”

Distal Myopathy with Rimmed Vacuoles Confirmed by Whole Exome Sequencing

“…This disease generally develops in early adulthood and is clinically characterized by preferential involvement of ankle dorsiflexors [1,20]. In addition, muscle pathology typically reveals muscle fiber atrophy with rimmed vacuoles and intracellular congophilic deposits [19].…”

“…The GNE gene is ubiquitously expressed and has two functional domains: the epimerase and the kinase domains located in the N-terminus encoding the N-actylglucosamine 2 epimerase and the C-terminus encoding the N-acetylmannosamine kinase, respectively [14,19]. Mutations in GNE have been linked to not only DMRV (MIM 605820) [27,29] but also sialuria (MIM 269921) [13,24].…”

Genetics of GNE myopathy in the non-Jewish Persian population

“…The Middle Eastern patients harboring c.2228T4C (p.M743T) became wheelchair bound on average 15 years after the disease onset, 5 whereas ambulatory loss occurred earlier in Indian (3-9 years after the disease onset) 25 and Japanese (12 years) 3 patients. Of our patients homozygous for c.830G4A (p.R277Q; Table 1), one (9b, 42 years) used a wheelchair intermittently (15 years after onset) and another (9a, 45) became wheelchair bound 13 years after onset.…”

“…As the disease progresses patients become wheelchair bound~10-12 years after onset. 3 The typical histopathological findings in GNE myopathy include cytoplasmic rimmed vacuoles and congophilic inclusions mainly in angular atrophic fibers, some arranged in groups using Gomori trichrome and Congo red stains. Presence of necrotic or basophilic degenerative fibers and endomysial fibrosis are not among usual findings but can be seen in typical cases.…”