Search

GNE myopathy is a rare neuromuscular disease whose description is fairly recent. It predominantly affects the adult population and is an inherited autosomal recessive disorder. Although universal and ubiquitous, GNE myopathy prevails in the Jewish community of Persian origin, living in Iran, Israel or in the United States. This condition has also been reported in great number in populations of far-East Asia (Japan and neighboring countries) and, closer to France, in Bulgaria. GNE myopathy causes muscle weakness in the extremities (distal myopathy), affecting initially and predominantly foot flexor muscles. The generic term of GNE myopathy is now fully accepted and encompasses two previously described entities: the quadriceps sparing myopathy, (also referred to as the autosomal recessive form of inclusion body myopathy (hIBM) and the Nonaka type distal myopathy (or distal myopathy with rimmed vacuoles DMRV). This myopathy is due to mutations in the GNE gene encoding a bifunctional enzyme, the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase. This enzyme plays a role at two levels in the metabolic pathway leading to the synthesis of sialic acid. Sialic acid, also known as N-acetylneuraminic acid (Neu5Ac or NANA), is a monosaccharide essential to other protein or lipid molecules requiring sugar residues on their surface in order to function efficiently. GNE myopathy is characterized by histological lesions (rimmed vacuoles) within muscle fibers. They are fairly typical in a suggestive context, but non-specific and inconsistent from one muscle to another. The diagnosis of GNE myopathy is essentially based on clinical clues, including muscle imaging, and is confirmed by genetic studies. If promising therapeutic trials are being developed to compensate for this recently unveiled metabolic defect, the treatment of this myopathy remains purely supportive to date., (© 2015 médecine/sciences – Inserm.)

Miyoshi myopathy is the most common form of recessive distal myopathy. Recessive mutations in the ANO5 gene have been recently identified in Northern Europe as a cause of non dysferlin-linked distal myopathy and limb girdle muscular dystrophy. We report here the first French cases of anoctamin 5 myopathy in 2 brothers presenting with a Miyoshi-like pattern. Comparing these patients with 12 other cases from the literature shows that all cases share a homogeneous clinical pattern, characterized by initial calf muscles involvement. Asymmetric muscle atrophy often precedes weakness. In this setting, high CK level and normal expression of dysferlin in muscle should lead to consider the diagnosis, which will be confirmed by ANO5 gene testing. The c.191dupA mutation, already reported as a founder mutation in Caucasian patients with anoctamin myopathies, was found in our family in a heterozygous state., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Distal myopathies are rare muscular disorders clinically characterized by a predominantly distal muscular involvement. Among recessive forms, the myopathy resulting from mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene, often designated as Nonaka myopathy, primarily affect young adults and are characterized by muscle wasting and weakness predominating on the anterior compartment of the leg, a remarkable quadriceps sparing and a frequent evolution towards ambulation loss after a few years. Finding rimmed vacuoles on muscle biopsy is a further argument for the diagnosis. However, the presentation and course may vary and we describe four patients who illustrate the clinical spectrum of the disease: the first patient had a classical form with progressive weakness over several years, the second one a rapidly progressive myopathy leading to ambulation loss within three years from onset, the third one a very slow course with no ambulation loss after several decades, and the last one a progressive form with misleading neurogenic features on the EMG. One of our four patients harbored a homozygous mutation, and three others were compound heterozygous, two of them displaying an original mutation: one had a c.2036 T>G (p.Val679Gly) substitution, the c.829 C>T (p.Arg277Cys) substitution.