Pulmonology Book

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Alpha-1-Antitrypsin Deficiency

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  1. Epidemiology
    1. Age of onset: 20 to 50 years
  2. 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)
  3. 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
  4. Labs
    1. Serum alpha-1 antitrypsin
      1. Deficiency: Level <1.5 g/L (<20 umol/L)
  5. 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)
  6. Complications
    1. Chronic Obstructive Pulmonary Disease (Emphysema)
    2. Neonatal Hepatitis
    3. Chronic Hepatitis (adults)
    4. Cirrhosis (and associated risk of Hepatocellular Carcinoma)
    5. Wegener's Granulomatosis (rare)
    6. Skin Necrotizing Panniculitis (rare)
  7. References
    1. Kohnlein (2008) Am J Med 121:3

alpha 1-Antitrypsin Deficiency (C0221757)

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.
Definition (MSH)Deficiency of the protease inhibitor ALPHA 1-ANTITRYPSIN, leading primarily to degradation of elastin of the alveolar walls, as well as other structural proteins of a variety of tissues. (From Scriver, Beaudet, Sly, & Valle, The Metabolic and Molecular Bases of Inherited Disease, 7th ed, p4125)
ConceptsDisease or Syndrome (T047)
ICD9273.4, 273.4
MSHD019896
EnglishAAT deficiency, ALPHA 1 ANTITRYPSIN DEFIC, alpha 1 antitrypsin deficiency, alpha 1-Antitrypsin Deficiencies, alpha 1-Antitrypsin Deficiency, ALPHA ANTITRYPSIN DEFICIENCY 01, ALPHA-1 ANTITRYPSIN DEFICIENCY, ALPHA-1-ANTITRYPSIN DEF, alpha-1-Antitrypsin deficiency, alpha-1-Proteinase inhibitor deficiency
Spanishdeficiencia de alfa - 1 - antitripsina, deficiencia de inhibidor de alfa - 1 - proteinasa
Parent ConceptsInborn Errors of Metabolism (C0025521), Disorder of plasma protein metabolism NOS (C0154253), Connective Tissue Diseases (C0009782), Lung diseases (C0024115), Autosomal recessive hereditary disorder (C0265388), [X]Disorder of glycoprotein metabolism, unspecified (C0342844), Metabolic and genetic disorder affecting the liver (C0400963), Enzymopathy (C0520572), Digestive system hereditary disorder (C1285252), Duplicate concept (C1274013)
SourcesCOSTAR, CSP, DXP, ICD9CM, MEDLINEPLUS, MSH, MTHICD9, NDFRT, SCTSPA, SNOMEDCT
Derived from the NIH UMLS (Unified Medical Language System)



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