Updated: 10/1/2019

Alpha-1 Antitrypsin Deficiency

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Snapshot
  • A 23-year-old man with a past medical history of depression presents to his primary care physician for increasing shortness of breath. He reports that this occurs especially when he exercises. His family history is pertinent for lung disease in multiple family members, but he is not sure which lung disease. He reports that when he smokes socially, the shortness of breath becomes acutely worse. A chest radiograph shows a flattened diaphragm, and laboratory evaluation reveals increased lever enzymes. He is sent to the genetic counselor for genetic testing.
Introduction
  • Clinical definition
    • alpha-1 antitrypsin deficiency is characterized by
      • early-onset emphysema
      • cirrhosis
  • Epidemiology
    • demographics
      • young adults
        • often without a history of smoking
    • risk factors
      • family history
      • smoking exacerbates illness
  • Pathogenesis
    • alpha-1 antitrypsin is a serine protease inhibitor synthesized in the liver
      • inhibits proteolysis by enzymes, particularly elastase
    • decrease or dysfunctional alpha-1 antitrypsin is usually caused by misfolded gene product
      • increased proteolysis of alveoli by neutrophil elastase
      • accumulation of the misfolded alpha-1 antitrypsin polymers in hepatocytes
      • proteolysis and damage to vessels may cause vasculitis
  • Genetics
    • autosomal codominant
    • SERPINA1 gene
Presentation
  • Symptoms
    • chronic obstructive pulmonary disease (COPD)
      • onset at age 40-50 years
      • dyspnea on exertion
      • wheezes
      • cough
      • sputum production
    • liver disease that may progress to cirrhosis
      • onset in childhood
      • hepatomegaly
      • abdominal pain
Imaging
  • Chest radiograph
    • findings
      • flattened diaphragm
  • Computed tomography of chest
    • findings
      • panacinar emphysema
Studies
  • Serum labs
    • ↑ prothrombin time
    • ↓ alpha-1 antitrypsin level
    • ↑ liver enzymes
    • genetic testing
      • confirms diagnosis
  • Invasive studies 
    • liver biopsy 
      • findings
        • PAS+ globules in hepatocytes
  • Diagnostic criteria
    • diagnosed with ↓ alpha-1 antitrypsin levels and confirmed with genetic testing or liver biopsy
Differential
  • Asthma 
    • distinguishing factor
      • typically not associated with liver disease and presents at a younger age
  • Autoimmune hepatitis 
    • distinguishing factor
      • typically not associated with COPD or ↓ alpha-1 antitrypsin levels
Treatment
  • Lifestyle
    • minimize alcohol consumption
  • Medical
    • vaccinations
      • influenza
      • pneumococcus
    • alpha-1 antitrypsin infusion
      • indication
        • patients with symptoms of COPD
    • standard COPD treatment
  • Surgical
    • liver transplant
      • indication
        • decompensated cirrhosis
        • hepatocellular carcinoma
      • outcomes
        • liver transplant will help patients maintain normal levels of donor’s alpha-1 antitrypsin
Complications
  • Hepatocellular carcinoma
    • regular surveillance
      • liver ultrasound
      • alpha-fetoprotein

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(M1.GI.15.22) A 36-year-old woman with no prior history of smoking presents to her primary care physician for recurrent dyspnea on exertion and shortness of breath. She used to be in good health but now gets very winded when she walks up a flight of stairs or a few city blocks. The physician obtains a chest radiograph which is demonstrated in figure F. The physician then orders pulmonary function tests which demonstrate: FEV1: 60% of normal, FVC: low-normal, FEV1/FVC: 0.57, DLCO: normal. The physician, concerned about the etiology of this patient's condition orders a liver biopsy. Which of the following figures represents the histological findings of this patient's liver biopsy?

QID: 104813
FIGURES:
1

Figure A

14%

(25/180)

2

Figure B

12%

(22/180)

3

Figure C

48%

(86/180)

4

Figure D

12%

(22/180)

5

Figure E

9%

(17/180)

M 1 D

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