RT Book, Section
A1 van der Knaap, Marjo S.
A1 Bugiani, Marianna
A1 Boor, Ilja
A1 Proud, Chris G.
A1 Scheper, Gert C.
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1181480196
T1 Vanishing White Matter
T2 The Online Metabolic and Molecular Bases of Inherited Disease
YR 2019
FD 2019
PB McGraw-Hill Education
PP New York, NY
SN 9780071459969
LK ommbid.mhmedical.com/content.aspx?aid=1181480196
RD 2024/04/20
AB “Vanishing  white  matter”  (VWM)  is  an  autosomal  recessively  inherited  disorder  in  which  the  basic  defect  resides  in  eukaryotic  initiation  factor  2B  (eIF2B).  The  clinical  onset  and  severity  of  VWM  vary  greatly.  The  classical  form  has  an  early-childhood  onset,  but  onset  can  vary  from  antenatal  and  early-infantile  onset  at  one  end  of  the  spectrum  to  late-adult  onset  at  the  other  end.  Age  of  onset  is  predictive  of  disease  severity.  The  clinical  and  histopathologic  manifestations  of  VWM  are  dominated  by  degeneration  of  the  white  matter  of  the  central  nervous  system.  Organs  other  than  the  brain  are  rarely  affected,  with  the  exception  of  the  ovaries.  In  addition  to  a  chronic  progressive  encephalopathy,  there  are  typically  episodes  of  rapid  and  major  deterioration,  provoked  by  stresses  like  febrile  infections  of  minor  head  trauma.  VWM  is  caused  by  mutations  in  any  of  the  five  genes  EIF2B1-5,  encoding  the  α-ϵ  subunits  of  eIF2B.  The  reason  for  the  selective  vulnerability  of  the  white  matter  of  the  central  nervous  system  and,  less  consistently,  the  ovaries  is  poorly  understood.  Multiple  hypotheses  have  been  put  forward,  including  the  effects  of  inappropriate  activation  of  the  unfolded  protein  response  in  oligodendrocytes  and  astrocytes,  differing  cellular  levels  of  eIF2B  or  eIF2/eIF2B  ratios  and  aberrant  control  of  translation  of  specific  mRNAs.