TY  - CHAP
M1  - Book, Section
TI  - Cytochrome b5 Reductase Deficiency and Enzymopenic Hereditary Methemoglobinemia
A1  - Jaffé, Ernst R.
A1  - Hultquist, Donald 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  major  pathway  for  the  reduction  of  methemoglobin  to  functional  hemoglobin  in  human  erythrocytes  involves  a  NADH-dependent  methemoglobin  reductase  system.  In  addition  to  NADH,  this  system  requires  the  presence  in  the  cytosol  of  both  cytochrome  b5  reductase,  a  32,000-dalton  protein,  and  cytochrome  b5,  a  12,000-dalton  protein.  These  proteins  are  presumed  to  arise  from  larger  parent  molecules  in  the  erythroid  precursors  by  proteolytic  cleavage  of  their  hydrophobic  tails.Enzymopenic  hereditary  methemoglobinemia  (MIM  250800)  is  a  rare  recessively  inherited  disorder  caused,  in  most  cases,  by  deficiency  of  cytochrome  b5  reductase  only  in  erythrocytes  (type  I).  Generalized  cytochrome  b5  reductase  deficiency,  demonstrable  in  all  tissues  that  have  been  examined,  occurs  in  10  to  15  percent  of  cases  and  is  accompanied  by  methemoglobinemia  and  severe,  progressive,  lethal  neurologic  disability  (type  II).  Cytochrome  b5  reductase  deficiency  limited  to  hematopoietic  cells  is  also  manifested  by  methemoglobinemia,  but  without  neurologic  effects  (type  III).  Deficiency  of  cytochrome  b5  may  also  lead  to  methemoglobinemia  (type  IV).The  gene  regulating  the  synthesis  of  cytochrome  b5  reductase  has  been  assigned  to  chromosome  22.  Deficiency  of  cytochrome  b5  reductase  has  a  worldwide  distribution,  and  electrophoretic  variants  of  the  enzyme  with  normal  catalytic  properties  may  have  an  incidence  as  high  as  1:100.  Heterozygotes  for  cytochrome  b5  reductase  deficiency  are  asymptomatic  but  have  an  increased  propensity  to  develop  toxic  methemoglobinemia  induced  by  drugs  or  other  chemicals.The  diagnosis  of  enzymopenic  hereditary  methemoglobinemia  may  be  made  by  relatively  simple  laboratory  determinations,  but  definition  of  the  specific  defect  requires  more  sophisticated  studies.Effective  treatment  may  be  provided  by  the  administration  of  methylene  blue,  ascorbic  acid,  or  riboflavin  but  is  often  not  indicated,  except  for  cosmetic  reasons.  Such  therapy,  however,  has  had  no  demonstrable  effect  on  the  neurologic  aberrations  in  the  generalized  type  II  disorder.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/19
UR  - ommbid.mhmedical.com/content.aspx?aid=1181456408
ER  -