title: Magnesium may help patients with recessive hereditary inclusion body myopathy, a pathological review.
abstract: Recently, bi-allelic mutations in the gene coding for the bi-functional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE/MNK), symbol GNE or GLCNE (MIM: 603824), were associated with the recessively inherited phenotype of IBM2 (MIM: 600737). All patients tested so far have bi-allelic missense mutation(s) of epimerase and/or kinase domains of GNE gene, which clearly explains the recessive inheritance pattern of this phenotype. Single allelic mutations of codons 263-266 of GNE have been implicated as the cause of French type sialuria (MIM: 269921). The dominantly inherited French type sialuria seems to result from defective allosteric feedback inhibitory regulation of GNE/MNK by cytidine monophosphate-N-acetylneuraminic acid (CMP-NANA), resulting in overproduction of cytosolic N-acetylneuraminic acid, and massive urinary excretion of free sialic acid. Because GNE is relatively weakly expressed in skeletal muscle cells, and involvement of other organs are not clinically evident in patients affected with IBM2, it is likely that the missense mutation(s) found in these patients cause a partial reduction of the efficiency of either the epimerase or the kinase activity of this enzyme. Therapeutic dietary modifications are recommended including reduction of ethanol consumption, avoidance of excess selenium, copper, and zinc, and dietary promotion of magnesium (Mg(2+)), which is an essential co-factor for this enzyme.
authors.affiliation: HIBM Research Group, Encino, CA 91434, USA. dd@hibm.org
authors.forename: D
authors.initials: D
authors.lastname: Darvish
mesh_terms: D000818:Animals; D002238:Carbohydrate Epimerases / Q000235:genetics; D005808:Genes, Recessive; D006801:Humans; D008274:Magnesium / Q000627:therapeutic use*; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D018979:Myositis, Inclusion Body / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D010641:Phenotype; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism
chemical_list: D012794:Sialic Acids; D017853:Phosphotransferases (Alcohol Group Acceptor); C018765:N-acylmannosamine kinase; D002238:Carbohydrate Epimerases; C100033:UDP acetylglucosamine-2-epimerase; D008274:Magnesium