TY  - CHAP
M1  - Book, Section
TI  - Hereditary Spherocytosis and Hereditary Elliptocytosis
A1  - Tse, William T.
A1  - Lux, Samuel E.
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  - The  red-blood-cell  membrane  is  composed  of  a  bilayer  of  lipids  and  integral  membrane  proteins  laminated  to  an  underlying  protein  skeleton.  The  membrane  skeleton  is  a  two-dimensional  meshwork  of  spectrin  tetramers  and  oligomers  cross-linked  by  protein  4.1  and  short  actin  filaments.  It  is  attached  to  the  membrane  via  the  binding  of  spectrin  to  ankyrin  and  ankyrin  to  band  3  protein  and  via  an  interaction  between  protein  4.1  and  glycophorin  C.  The  membrane  skeleton  is  a  major  determinant  of  membrane  shape,  strength,  and  flexibility  and  helps  to  control  lipid  organization  and  integral  protein  mobility  and  topography.  Genetic  defects  in  the  red  cell  membrane  or  its  skeleton  cause  congenital  hemolytic  disorders  or  inherited  abnormalities  in  red  cell  morphology  such  as  hereditary  elliptocytosis  and  hereditary  spherocytosis.Hereditary  elliptocytosis  (HE)  is  a  heterogeneous  group  of  congenital  red  cell  disorders  characterized  by  ellipsoidally  shaped  cells.  Hereditary  pyropoikilocytosis  (HPP)  is  a  related  and  more  severe  group  of  disorders  characterized  by  fragmented  red  cells  and  poikilocytes.  The  clinical  phenotypes  of  HE  and  HPP  are  a  continuous  spectrum  with  varying  degrees  of  severity.  Common  HE  is  usually  a  mild,  dominantly  inherited  condition  with  prominent  elliptocytosis  but  little  or  no  hemolysis.  Acute  hemolytic  episodes  sometimes  occur  in  patients  when  splenomegaly  develops  in  response  to  exogenous  stimuli.  Some  patients  with  common  HE  present  with  poikilocytosis  and  hemolysis  in  infancy  but  later  improve  and  are  clinically  mild  after  the  first  year  of  life.  In  the  occasional  patients  with  homozygous  HE,  severe  hemolysis  is  observed.  Similar  features  are  observed  in  HPP,  an  uncommon,  usually  sporadic  disorder  manifest  by  severe  hemolysis,  marked  poikilocytosis,  and  increased  sensitivity  of  red  cells  to  heat-induced  fragmentation.  HPP  patients  often  have  family  members  who  have  common  HE,  and  their  severe  phenotype  can  be  explained  by  the  coinheritance  of  an  HE  allele  and  a  disease-modifying  gene.Many  defects  in  membrane  skeletal  proteins  have  been  identified  in  patients  with  HE  and  HPP.  Isolated  skeletons  from  these  patients  retain  the  elliptocytic  or  poikilocytic  shape  of  the  original  red  cells,  indicating  that  the  defect  causing  the  abnormal  shape  is  intrinsic  to  the  membrane  skeleton.  Many  HE/HPP  patients  have  spectrins  that  are  heat-sensitive  and  defective  in  spectrin  tetramer  formation,  and  that  cleave  abnormally  with  proteases.  Molecular  analysis  often  demonstrate  point  mutations  or  small  deletions  in  the  α-  or  β-spectrin  genes  that  interfere  with  tetramer  formation.  A  low-expression  α-spectrin  allele,  αLELY  spectrin,  is  found  at  a  high  frequency  in  most  populations.  When  αLELY  spectrin  is  coinherited  in  trans  to  an  HE  α-spectrin  allele,  it  markedly  aggravates  the  clinical  severity  of  the  disease,  explaining  the  sporadic  occurrence  of  clinically  severe  HPP  patients  in  common  HE  families.  Other  HE/HPP  patients  have  deficient  or  abnormal  protein  4.1  that  weakens  the  skeleton  protein  meshwork.  A  small  number  of  patients  with  very  mild  HE  have  glycophorin  C  deficiency.Hereditary  spherocytosis  (HS)  is  a  congenital  hemolytic  anemia  characterized  by  spheroidally  shaped  red  cells  with  a  reduced  surface  area-to-volume  ratio,  due  to  a  progressive  loss  of  the  plasma  membrane.  These  spherocytes  are  mechanically  rigid,  osmotically  fragile,  and  selectively  retained  in  the  spleen  and  destroyed.  Patients  with  the  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/18
UR  - ommbid.mhmedical.com/content.aspx?aid=1181457681
ER  -