TY  - CHAP
M1  - Book, Section
TI  - The Hereditary Hemochromatoses
A1  - Brooks, David G.
A2  - Murray, Michael F.
A2  - Babyatsky, Mark W.
A2  - Giovanni, Monica A.
A2  - Alkuraya, Fowzan S.
A2  - Stewart, Douglas R.
PY  - 2014
T2  - Clinical Genomics: Practical Applications in Adult Patient Care
AB  - Disease  summary:Iron  is  an  essential  dietary  mineral  that  can  become  toxic  when  present  in  excess  quantities  or  in  a  reactive  state.Hereditary  hemochromatosis  (HHC)  is  defined  as  a  biochemical  state  of  iron  overload  complicated  by  end-organ  dysfunction  such  as  diabetes,  cirrhosis,  or  cardiomyopathy.It  is  critical  to  recognize  the  general  presenting  symptoms  or  family  history  of  HHC  as  this  disease  can  be  fatal  if  undiagnosed,  but  is  the  rare  genetic  disease  that  can  be  cured  if  detected  and  treated  early.The  HHCs  are  a  group  of  monogenic  diseases  with  a  common  pathophysiology  that  features  disruption  of  mechanisms  regulating  iron  homeostasis  resulting  in  excess  iron  accumulation.The  most  common,  classical  form  of  the  disease  is  type  1  or  HFE-linked  HHC  which  accounts  for  80%  of  cases  in  Caucasian  populations.  The  other  types  are  rare  and  panethnic.There  are  four  other  well-defined  types  of  hereditary  hemochromatosis  caused  by  loss-of-function  mutations  in  five  genes.The  common  pathophysiology  underlying  HHC  is  failure  to  prevent  a  rise  in  blood  iron  levels  as  evidenced  by  the  fact  that  all  five  proteins  either  sense  or  control  the  level  of  iron.Hereditary  basis:Iron  overload  should  only  be  attributed  to  hereditary  causes  after  ruling  out  comorbid  conditions  such  as  other  etiologies  of  liver  disease  or  anemia  that  lead  to  secondary  iron  overload.Types  1  to  3  HHC  are  autosomal  recessive  and  result  from  loss-of-function  mutations.Type  4  is  autosomal  dominant  due  to  heterozygous  mutations  of  ferroportin  with  two  distinct  genotype-phenotype  manifestations.Differential  diagnosis:The  key  is  to  distinguish  uncomplicated  iron  overload  from  complicated  iron  overload  that  includes  HHC.It  is  imperative  to  differentiate  other  causes  of  liver  disease  where  iron  accumulation  is  secondary  (eg,  alcoholic  or  hepatitis  virus  cirrhosis)  from  HHC.Other  genetic  disorders  such  as  anemias  and  porphyria  cutanea  tarda  are  associated  with  secondary  iron  overload  but  have  additional  features  that  distinguish  them  from  HHC.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/18
UR  - accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102702187
ER  -