title: Role of alpha-1-antichymotrypsin deficiency in promoting cirrhosis in two siblings with heterozygous alpha-1-antitrypsin deficiency phenotype SZ.
abstract: BACKGROUND
  Alpha-1-antitrypsin (A1AT) deficiency is the most common inherited metabolic disorder with the potential to cause injury in the lung and liver. Recent reports suggested that alpha-1-antichymotrypsin (A1AC) deficiency may also be a possible cause of chronic liver disease. However, it has received little attention and is rarely investigated in the clinical setting.
  
  
  OBJECTIVE
  To assess the role of A1AC deficiency in the pathogenesis of chronic liver disease in two siblings with heterozygous A1AT phenotype Pi SZ.
  
  
  METHODS
  Two adult siblings with an A1AT Pi SZ phenotype and reduced levels of A1AC consistent with heterozygosity who developed cirrhosis and underwent liver transplantation.
  
  
  RESULTS
  A1AT and A1AC levels in plasma measured by electroimmunoassay were 74 mg/dl and 90 mg/dl (140-470) and 0.12 mg/ml and 0.14 mg/ml (0.173-0.46), respectively. Immunohistochemistry revealed an apparent accumulation of both A1AT and A1AC in hepatocytes. A previously reported point mutation in exon III (Pro(229) to Ala substitution) of the A1AC gene was not detected by polymerase chain reaction amplification and a single strand conformation polymorphism analysis.
  
  
  CONCLUSIONS
  Our report represents the first case of two siblings with A1CA phenotype Pi SZ who developed cirrhosis and underwent liver transplantation. Both siblings were heterozygous for A1AT and A1AC deficiency suggesting that combined deficiency of these two major serine protease inhibitors may enhance the risk of developing liver disease.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Veterans Affairs Medical Center, Houston, Texas 77030, USA.
authors.forename: D
authors.initials: D
authors.lastname: Yoon
authors.forename: F
authors.initials: F
authors.lastname: Kueppers
authors.forename: R M
authors.initials: RM
authors.lastname: Genta
authors.forename: G B
authors.initials: GB
authors.lastname: Klintmalm
authors.forename: V I
authors.initials: VI
authors.lastname: Khaoustov
authors.forename: B
authors.initials: B
authors.lastname: Yoffe
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D000514:alpha 1-Antichymotrypsin / Q000172:deficiency*; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications*
chemical_list: D000514:alpha 1-Antichymotrypsin