II. Epidemiology

  1. Age of onset: 20 to 50 years

III. Pathophysiology

  1. Serpina1 gene defect (Chromosome 14q31-32.3) results in Alpha-1 antitrypsin deficiency
  2. Alpha-1 antitrypsin protects against the Leukocyte enzyme Neutrophil elastase
  3. When Alpha-1 antitrypsin is deficient, neutophil elastase results in tissue damage
    1. Lung alveolar damage (most common)
    2. Liver injury (less common)
    3. Skin Injury (rare)

IV. Presentations: Clinical manifestations that warrant screening

  1. Emphysema onset before age 45 years
  2. Emphysema without Tobacco exposure or occupational exposure
  3. Emphysema predominantly affecting the lower lung lobes
  4. Idiopathic Chronic Hepatitis
  5. Family History of COPD or Bronchiectasis at a young age or without risk factors

V. Labs

  1. Serum alpha-1 antitrypsin
    1. Deficiency: Level <1.5 g/L (<20 umol/L)

VI. Management

  1. See COPD Management
  2. Eliminate exacerbating exposures
    1. Avoid Tobacco exposure
    2. Avoid occupational exposures of airborne toxins
  3. Substitution therapy with human alpha-1 antitrypsin
    1. Weekly injection of alpha-1-antitrypsin (60 mg/kg) from pooled human plasma
    2. Indicated in non-smokers, progressive COPD, and serum level <0.8 g/L (<11 umol/L)

VII. Complications

  1. Chronic Obstructive Pulmonary Disease (Emphysema)
  2. Neonatal Hepatitis
  3. Chronic Hepatitis (adults)
  4. Cirrhosis (and associated risk of Hepatocellular Carcinoma)
  5. Granulomatosis with Polyangiitis (previously known as Wegener's Granulomatosis, rare)
  6. Skin Necrotizing Panniculitis (rare)

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Related Studies

Ontology: alpha 1-Antitrypsin Deficiency (C0221757)

Definition (MSH) Deficiency of the protease inhibitor ALPHA 1-ANTITRYPSIN that manifests primarily as PULMONARY EMPHYSEMA and LIVER CIRRHOSIS.
Definition (MEDLINEPLUS)

Alpha-1 antitrypsin deficiency (AAT deficiency) is an inherited condition that raises your risk for lung and liver disease. Alpha-1 antitrypsin (AAT) is a protein that protects the lungs. The liver makes it. If the AAT proteins aren't the right shape, they get stuck in the liver cells and can't reach the lungs.

Symptoms of AAT deficiency include

  • Shortness of breath and wheezing
  • Repeated lung infections
  • Tiredness
  • Rapid heartbeat upon standing
  • Vision problems
  • Weight loss

Some people have no symptoms and do not develop complications.

Blood tests and genetic tests can tell if you have it. If your lungs are affected, you may also have lung tests. Treatments include medicines, pulmonary rehab, and extra oxygen, if needed. Severe cases may need a lung transplant. Not smoking can prevent or delay lung symptoms.

NIH: National Heart, Lung, and Blood Institute

Definition (NCI) A genetic disorder characterized by decreased alpha-1 antitrypsin activity in the lungs and blood and deposition of alpha-1 antitrypsin protein in the hepatocytes. These abnormalities result from defective production of alpha-1 antitrypsin and lead to the development of emphysema, cirrhosis, and liver failure.
Definition (CSP) autosomal recessive trait leading to destruction of lung tissue by neutrophil elastase and eventual emphysema; second only to cystic fibrosis as most common lethal genetic disorder among Caucasians of northern European ancestry.
Concepts Disease or Syndrome (T047)
MSH D019896
ICD9 273.4
ICD10 E88.01
SnomedCT 30188007, 154771007
English Deficiencies, alpha 1-Antitrypsin, Deficiency, alpha 1-Antitrypsin, alpha 1 Antitrypsin Deficiency, alpha 1 antitrypsin deficiency, alpha 1-Antitrypsin Deficiencies, ALPHA ANTITRYPSIN DEFICIENCY 01, ALPHA 1 ANTITRYPSIN DEFIC, alpha 1-antitrypsin deficiency, alpha 1-antitrypsin deficiency (diagnosis), Alpha-1-antitrypsin deficiency (disorder), alpha-1-Antitrypsin deficiency (disorder), alpha-1-Antitrypsin deficiency, Alpha-1-antitrypsin deficiency, Alpha-1 anti-trypsin deficiency, Alpha-1 proteinase inhibitor deficiency, Alpha-1-antitrypsin def, A-1ATD, A1AD, AAT deficiency, alpha 1-Antitrypsin Deficiency [Disease/Finding], alpha-1 antitrypsin deficiency, alpha-1-antitrypsin deficiency, 1 alpha antitrypsin deficiency, alpha-1 anti-trypsin deficiency, ALPHA-1-ANTITRYPSIN DEFICIENCY, AATD, Alpha-1 Antitrypsin Deficiency, alpha 1-Antitrypsin Deficiency, Alpha 1-antitrypsin deficiency, Alpha-1-Antitrypsin Deficiency, alpha-1-Proteinase inhibitor deficiency, deficiency; alpha-1-antitrypsin, alpha-1-antitrypsin; deficiency, Deficiency;A1 antitrypsin
Italian Deficit di alfa-1 antitripsina, Deficit dell'inibitore della alfa-1 proteinasi, Deficit di alfa-1-antitripsina
Dutch alfa-1-proteïnase-inhibitordeficiëntie, alfa-1-antitrypsine; deficiëntie, deficiëntie; alfa-1-antitrypsine, alfa-1-antitrypsinedeficiëntie, Alfa-1-antitrypsinedeficiëntie, Antitrypsinedeficiëntie, alfa-1-, Deficiëntie, alfa-1-antitrypsine-
French Carence en inhibiteurs de la protéinase alpha-1, Déficit en alpha 1-antitrypsine, Déficit en alpha-1-antitrypsine, Déficit en alpha-1 antitrypsine
German Alpha-1 Proteinase-Inhibitormangel, ALPHA ANTITRYPSINMANGEL 01, Alpha-1 Antitrypsinmangel, Alpha-1-Antitrypsinmangel
Portuguese Carência de inibidor de alfa-1-proteinase, Deficiência de 1-Antitripsina alfa, Deficiência de alfa-1-antitripsina, Deficiência de alfa 1-Antitripsina
Spanish Déficit del inhibidor de la alfa-1 proteínasa, deficiencia de alfa-1-antitripsina, deficiencia de inhibidor de alfa - 1 - proteinasa, deficiencia de alfa - 1 - antitripsina (trastorno), deficiencia de alfa-1-antitripsina (trastorno), Deficiencia de alfa 1-Antitripsina, deficiencia de alfa - 1 - antitripsina, Déficit de alfa-1 anti-tripsina
Japanese α1蛋白分解酵素阻害欠損症, α1抗トリプシン欠損症, アルファ1タンパクブンカイコウソソガイケッソンショウ, アルファ1コウトリプシンケッソンショウ, アルファ1-アンチトリプシン欠損症, α1-アンチトリプシン欠損症
Swedish Alfa 1-antitrypsinbrist
Finnish Alfa-1-antitrypsiinin puutos
Czech Deficit alfa-1-antitrypsinu, Deficit inhibitoru alfa-1-proteinázy, alfa-1-antitrypsin - nedostatečnost, deficit alfa-1 antitrypsinu, deficit alfa-1- antitrypsinu, deficit α1-antitrypsinu, deficit alfa1-antitrypsinu
Polish Niedobór alfa-1-antytrypsyny
Hungarian Alpha-1 antitrypsin hiány, Alpha-1 proteinase inhibitor hiány
Norwegian Alfa-1-antitrypsinmangel