FaCD Online Syndrome Fact Sheet

Last updated: 13 May 2010

Name: Alpha-1-Antitrypsin Deficiency

Mode of Inheritance: AD

OMIM number: 107400  


PI, mapped to 14q32.1

Tumor features

hepatocellular cancer (hepatoma)
lung/bronchial cancer

Tumor features (possible)

colorectal cancer

Non-tumor features

liver cirrhosis
lung emphysema


This disorder is caused by deficiency of alpha-1-antitrypsin (= protease inhibitor = anti-elastase) and is characterized by emphysema and juvenile or adult liver cirrhosis. The severity of the disease depends on the specific combination of alleles and very likely also on the influence of exogenous factors like smoking. The homozygous null allele combination causes the most severe disease, followed by the ZZ combination.

Risk of hepatocellular cancer is increased, possibly only in males [1,2] and depending on allele type [3]. It has been reported in children[4]. Alpha-1-antitrypsin deficiency/haplosufficiency is a risk factor for lung cancer[5]. In one recent study, Alpha-1-ATD carriers were shown to be at a 70% to 100% increased risk of lung cancer and this genetic risk factor accounted for 11% to 12% of the patients with lung cancer in that study[7]. Yang et al.[6] estimated a 20-fold increase in risk to develop colorectal cancer (with microsatellite instability, MSI-H) among smokers who carry alpha-1-antitrypsin deficiency alleles.


Alpha-1 Association, USA 18 1 08


[1] Eriksson S, Carlson J, Velez R. Risk of cirrhosis and primary liver cancer in alpha1-antitrypsin deficiency. N Engl J Med 1986; 314(12):736-739.
[2] Rudnick DA, Perlmutter DH. Alpha-1-antitrypsin deficiency: a new paradigm for hepatocellular carcinoma in genetic liver disease. Hepatology (Baltimore, Md.) 2005; 42(3):514-21.
[3] Fargion S, Klasen EC, Lalatta F, Sangalli G, Tommasini M, Fiorelli G. Alpha1-antitrypsin in patients with hepatocellular carcinoma and chronic active hepatitis. Clin Genet 1981; 19:134-139.
[4] Hadzic N, Quaglia A, Mieli-Vergani G. Hepatocellular carcinoma in a 12-year-old child with PiZZ alpha1-antitrypsin deficiency. Hepatology (Baltimore, Md.) 2006; 43(1):194.
[5] Wentzlaff K, Marks R, Knutson A, Tazelaar H, Lindor N, Yang P. Family history of lung cancer patients who are alpha1-antitrypsin deficiency carriers. Am J Hum Genet 63suppl[4], A100. 1998.
[6] Yang P, Cunningham J, Katzmann J, Lesnick T, Halling K, Bugart L, Wiegert E, Christensen E, Kyle R, Lindor N, Thibodeau S. A 20-fold increase in risk of colorectal cancer with defective mismatch repair among current smokers who carry alpha-1 antitrypsin deficiency alleles. Am J Hum Genet 65[4], A40. 1999.
[7] Yang P, Sun Z, Krowka MJ, Aubry MC, Bamlet WR, Wampfler JA, Thibodeau SN, Katzmann JA, Allen MS, Midthun DE, Marks RS, de Andrade M. Alpha1-antitrypsin deficiency carriers, tobacco smoke, chronic obstructive pulmonary disease, and lung cancer risk.Arch Intern Med. 2008 May 26;168(10):1097-103.