Expanding the clinicopathological-genetic spectrum of GNE myopathy by a Chinese neuromuscular centre

Abstract

GNE myopathy is a heterogeneous group of ultrarare neuromuscular disorders caused by mutations in the GNE gene. An estimated prevalence of 1~21/1,000,000 leads to a deficiency of data and a lack of availability of samples to conduct clinical research on this neuromuscular disorder. Although GNE, which is the mutated gene responsible for the disease, is well known as the key enzyme in the biosynthesis pathway of sialic acid, the clinicopathological-genetic spectrum of GNE mutant patients is still unclear and expanding. This study presents ten unrelated patients with GNE myopathy, discovering five novel missense mutations. Clinical, electrophysiological, imaging, pathological and genetic data are presented in a retrospective manner. Interestingly, several patients in the cohort were found to have peripheral neuropathy and inflammatory cell infiltration in muscle biopsies, which have seldom been reported. This study, conducted by a neuromuscular centre in China, is the first attempt to highlight these abnormal clinicopathological features and associate them with genetic mutations in GNE myopathy.

Keywords: GNE mutation; GNE myopathy; muscle pathology; myopathy; neuromuscular disorder.

FIGURE 1

MRI in patient No.5 revealed increased signal intensity of the femur shaft and hamstrings; MRI in patient No.6 revealed pronounced fatty infiltration along with muscle atrophy in the posterior and internal compartments of the thigh muscles and lower leg muscles. (A and B), coronal axial MRI image of thigh muscles in patient No.5. (C and D), transverse axial image of thigh muscles in patient No.6. (E and F), transverse axial image of lower leg muscles in patient No.6

FIGURE 2

Myopathological changes in patients with GNE myopathy. All specimens were obtained from skeletal muscle. HE staining showed increased fibre size variation (A, G), vacuoles (A), fascial inflammation (D), atrophy (A, G) and regeneration (G). Modified Gömöri trichrome staining showed vacuoles (B) and rimmed vacuoles (E, H) in the fibres. NADH staining showed cores (C, I) and myofibrillar network disarray (F). Scale bar = 50 μm

FIGURE 3

Myopathological changes under electron microscopy in patient No.1 showed atrophic muscle fibres, a dilated sarcoplasmic reticulum and some oedematous and vacuolated mitochondria