PONM14 A novel homozygous missense mutation in the GNE gene of two brothers with hereditary inclusion body myopathy type 2

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 81; no. 11; p. e64
• Main Authors: Sheerin, U M, Lane, R J M, Rakowicz, W, Roncaroli, F
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.11.2010; BMJ Publishing Group LTD
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp.2010.226340.187

Hereditary inclusion body myopathy type 2 (HIBM2) is an autosomal recessive neuromuscular disorder presenting in early adulthood with foot drop and progressive muscle weakness that involves all limbs but typically spares the quadriceps, a unique feature of this disorder. Muscle histopathology reveals rimmed vacuoles on Gomoris trichrome stain, small fibres in groups and tubulofilaments without evidence of inflammation. The disorder is caused by a mutation in the gene for UDP-N-acetylglucosamine 2-epimerase-N-acetylmannosamine kinase (GNE), a bifunctional enzyme involved in protein glycosylation. We present two siblings from consanguineous parentage presenting several years apart with progressive lower extremity weakness. Clinical presentation, laboratory evaluation, electrophysiology, imaging, muscle pathology and genetic sequencing are described. The diagnosis was not suspected until the second sibling presented with distal weakness. A novel homozygous mutation c.568C>A changing leucine to isoleucine (p.L190I) in the epimerase domain was found confirming the diagnosis of hereditary inclusion body myopathy type 2. HIBM2 should be considered in patients presenting in their second or third decade with progressive lower- and upper-limb muscle weakness sparing the quadriceps with a pedigree consistent with an autosomal recessive disorder.