TY  - CHAP
M1  - Book, Section
TI  - Alpha-1 Antitrypsin Deficiency
A1  - Stoller, James K.
A2  - Murray, Michael F.
A2  - Babyatsky, Mark W.
A2  - Giovanni, Monica A.
A2  - Alkuraya, Fowzan S.
A2  - Stewart, Douglas R.
Y1  - 2014
N1  - 
T2  - Clinical Genomics: Practical Applications in Adult Patient Care
AB  - Disease  summary:Alpha-1  antitrypsin  (AAT)  deficiency  is  an  autosomal  codominant  condition  characterized  by  a  decrease  in  the  circulating  level  of  AAT,  a  member  of  the  serine  protease  inhibitor  (serpin)  family  of  proteins.  AAT  neutralizes  several  proteolytic  enzymes,  most  notably  neutrophil  elastase,  which  can  break  down  matrix  proteins  of  the  lung  like  elastin.  Emphysema  results  from  the  unopposed  proteolytic  burden  to  the  lung  that  is  abetted  by  decreased  levels  of  AAT.The  most  common  severe  deficient  variant  of  the  AAT  allele  (ie,  the  Z  allele)  is  also  characterized  by  intrahepatocyte  polymerization  and  accumulation  of  the  Z-type  AAT  protein,  with  resultant  cirrhosis  and/or  hepatoma.  In  the  genetic  variants  of  AAT  deficiency  that  are  characterized  by  intrahepatocyte  accumulation  of  unsecreted  AAT  (eg,  Z,  Mmalton),  different  pathogenetic  mechanisms  cause  the  liver  versus  the  lung  disease.  Liver  disease  results  from  a  toxic  gain  of  function,  which  can  trigger  cirrhosis  and/or  hepatoma  (by  incompletely  understood  mechanisms).  Lung  disease  results  from  the  unopposed  proteolytic  burden  to  the  lung  that  exists  when  levels  of  AAT  are  decreased  and  worsened  by  increased  lung  inflammation,  as  from  cigarette  smoking.In  addition  to  associations  with  emphysema  and  liver  disease  as  clinical  manifestations  of  AAT  deficiency,  panniculitis  and  C-ANCA-positive  vasculitis  have  been  established  to  be  associated  with  AAT  deficiency.Guidelines  recommend  testing  for  AAT  deficiency  in  all  symptomatic  adults  with  fixed  airflow  obstruction  on  postbronchodilator  spirometry,  as  well  as  individuals  with  panniculitis,  patients  with  otherwise  unexplained  cirrhosis,  unexplained  bronchiectasis,  and  siblings  of  AAT-deficient  individuals.Hereditary  basis:AAT  deficiency  is  inherited  as  an  autosomal  codominant  condition.The  gene  for  AAT,  SERPINA1,  is  located  on  chromosome  14  (14q32.1).Genetic  modifiers  of  pulmonary  risk  have  been  proposed  and  remain  the  subject  of  active  investigation.Differential  diagnosis:AAT  deficiency  should  be  considered  in  the  differential  diagnosis  of  various  pulmonary,  hepatic,  and  dermatologic  conditions,  including  emphysema,  chronic  bronchitis,  bronchiectasis,  or  even  asthma  in  which  a  component  of  fixed  airflow  obstruction  exists,  panniculitis,  cirrhosis,  chronic  hepatitis,  hepatoma,  and  C-ANCA-positive  vasculitis.While  AAT  deficiency  should  be  considered  in  all  symptomatic  adults  with  fixed  airflow  obstruction,  features  of  emphysema  that  might  further  heighten  suspicion  include  basilar-predominant  hyperlucency  on  chest  imaging,  early-onset  emphysema  (eg,  before  age  55),  occurrence  of  emphysema  in  a  non-  or  trivial-smoker,  or  a  family  history  of  liver  or  lung  disease.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/18
UR  - accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102704521
ER  -