title: Serum neural cell adhesion molecule is hyposialylated in hereditary inclusion body myopathy.
abstract: Hereditary inclusion body myopathy (HIBM) is a young-adult onset autosomal recessive disorder caused by a hypomorphic rate limiting enzyme of sialic acid biosynthesis. The enzyme is UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, and is encoded by the GNE gene. HIBM causes slowly progressive muscle weakness and atrophy. Patients are typically diagnosed at 20-30 years of age, and most patients are incapacitated and wheelchair-confined by 30-50 years of age. Some sialic acid containing glycoproteins, including neural cell adhesion molecule (NCAM), are hyposialylated in HIBM muscle biopsy samples. We developed a method to allow detection of serum NCAM sialylation using Western blot, and tested serum samples from several patients and a HIBM mouse model. Preliminary results showed a clear difference in polysialylated and hyposialylated forms of NCAM extracted from serum, and showed NCAM is hyposialylated in HIBM serum samples. This initial finding may prove useful in reducing the need for serial muscle biopsies in HIBM treatment trials. Additional studies are underway to further validate this finding and to evaluate the specificity, reliability, and robustness of this potential serum biomarker for HIBM.
authors.affiliation: HIBM Research Group, Reseda, California, USA. yadira@hibm.org
authors.forename: Yadira
authors.initials: Y
authors.lastname: Valles-Ayoub
authors.forename: Saghi
authors.initials: S
authors.lastname: Esfandiarifard
authors.forename: Pedram
authors.initials: P
authors.lastname: Sinai
authors.forename: Rosangela
authors.initials: R
authors.lastname: Carbajo
authors.forename: Zeshan
authors.initials: Z
authors.lastname: Khokher
authors.forename: Daniel
authors.initials: D
authors.lastname: No
authors.forename: Marvin
authors.initials: M
authors.lastname: Pietruszka
authors.forename: Babak
authors.initials: B
authors.lastname: Darvish
authors.forename: Emil
authors.initials: E
authors.lastname: Kakkis
authors.forename: Daniel
authors.initials: D
authors.lastname: Darvish
mesh_terms: D000328:Adult; D000818:Animals; D015153:Blotting, Western; D002238:Carbohydrate Epimerases / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D018979:Myositis, Inclusion Body / Q000151:congenital* / Q000235:genetics / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000097:blood*; D055815:Young Adult
chemical_list: D019006:Neural Cell Adhesion Molecules; D002238:Carbohydrate Epimerases; C100033:UDP acetylglucosamine-2-epimerase; D019158:N-Acetylneuraminic Acid