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Biochim Biophys Acta. 2009 Sep;1792(9):881-7. doi: 10.1016/j.bbadis.2009.07.001. Epub 2009 Jul 24.

Hereditary inclusion body myopathy: a decade of progress.

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1
Cell Biology of Metabolic Disorders Unit, National Human Genome Research Institute, National institutes of Health, Bethesda, MD 20892, USA.

Abstract

Hereditary Inclusion Body Myopathy (HIBM) is an autosomal recessive, quadriceps sparing type commonly referred to as HIBM but also termed h-IBM or Inclusion Body Myopathy 2 (IBM2). The clinical manifestations begin with muscle weakness progressing over the next 10-20 years uniquely sparing the quadriceps until the most advanced stage of the disease. Histopathology of an HIBM muscle biopsy shows rimmed vacuoles on Gomori's trichrome stain, small fibers in groups and tubulofilaments without evidence of inflammation. In affected individuals distinct mutations have been identified in the GNE gene, which encodes the bifunctional enzyme uridine diphospho-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase/N-acetyl-mannosamine (ManNAc) kinase (GNE/MNK). GNE/MNK catalyzes the first two committed steps in the biosynthesis of acetylneuraminic acid (Neu5Ac), an abundant and functionally important sugar. The generation of HIBM animal models has led to novel insights into both the disease and the role of GNE/MNK in pathophysiology. Recent advances in therapeutic approaches for HIBM, including administration of N-acetyl-mannosamine (ManNAc), a precursor of Neu5Ac will be discussed.

PMID:
19596068
PMCID:
PMC2748147
DOI:
10.1016/j.bbadis.2009.07.001
[Indexed for MEDLINE]
Free PMC Article

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