TY  - CHAP
M1  - Book, Section
TI  - GNE Myopathy
A1  - Huizing, Marjan
A1  - Malicdan, May Christine V.
A1  - Krasnewich, Donna M.
A1  - Manoli, Irini
A1  - Carrillo-Carrasco, Nuria
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
PY  - 2019
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - GNE  myopathy  is  a  rare  muscle  disease  caused  by  mutations  in  GNE,  the  gene  that  encodes  the  rate-limiting  enzyme  of  the  biosynthetic  pathway  of  sialic  acid.Uridine  diphosphate  (UDP)-N-acetylglucosamine  (GlcNAc)  2-epimerase/N-acetylmannosamine  (ManNAc)  kinase  (GNE)  catalyzes  the  first  2  committed  steps  in  sialic  acid  synthesis  and  is  encoded  by  the  GNE  gene.GNE  myopathy  patients  have  nonallosteric,  biallelic,  predominantly  missense  mutations  in  GNE.  GNE  myopathy  has  historically  also  been  named  hereditary  inclusion  body  myopathy  (HIBM),  distal  myopathy  with  rimmed  vacuoles  (DMRV),  Nonaka  myopathy,  inclusion  body  myopathy  type  2  (IBM2),  and  quadriceps-sparing  myopathy  (QSM).GNE  myopathy  presents  in  early  adulthood  with  lower  extremity  distal  muscle  weakness.  The  disease  is  characterized  by  a  slow  progression  of  muscle  weakness  and  atrophy,  from  distal  to  proximal,  initially  in  the  lower  extremities,  with  relative  sparing  of  the  quadriceps,  and  subsequently  in  the  upper  extremities.  The  disease  leads  to  marked  disability,  wheelchair  use,  and  dependent  care.The  diagnosis  of  GNE  myopathy  is  currently  based  upon  clinical  features,  muscle  pathology,  and,  ultimately,  the  presence  of  GNE  gene  mutations.  Histopathology  of  muscle  biopsies  typically  shows  rimmed  vacuoles  and  characteristic  filamentous  inclusions,  but  may  be  negative.  Diagnosis  is  usually  delayed  or  missed,  likely  because  of  the  rare  nature  of  the  disease  and  the  lack  of  inexpensive  and  noninvasive  diagnostic  tests.Impaired  sialylation  of  (muscle)  glycans  likely  underlies  the  disease  pathology.  However,  the  exact  pathophysiology  of  GNE  myopathy  remains  unknown.No  approved  therapies  are  currently  available  for  GNE  myopathy.  Clinical  trials  are  being  conducted,  including  trials  that  increase  sialic  acid  levels  through  exogenous  means  or  through  GNE  gene  therapy.  Exogenous  therapies  include  oral  administration  of  the  sialic  acid  precursor  N-acetylmannosamine  (ManNAc)  or  sialic  acid  (Neu5Ac)  itself  and  intravenous  administration  of  immunoglobulin  (IVIG),  a  highly  sialylated  compound.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/25
UR  - ommbid.mhmedical.com/content.aspx?aid=1184073424
ER  -