Alpha1-antitrypsin deficiency

Write about Alpha1-antitrypsin deficiency here.


• Alpha1-antitrypsin is a Serine Protease Inhibitors (deficiency = serpinopathy) controlling inflammatory cascades

• Synthesised in the liver, making up 90% of serum alpha1-globulin on electrophoresis

Alpha1-antitrypsin deficiency is the chief genetic cause of liver disease in children

• In adults => emphysema, chronic liver disease and HCC

Prevalence = 1:2000 - 1:7000


• Genetics:

• Carrier frequency 1:10

• Variants = Medium (M), Slow (S), Very Slow (Z)

• Reduced production of alpha1-antitrypsin (S=60%, Z = 15%)

• Normal  = PIMM, homozygote = PIZZ, hetero = PIMZ & PISZ


• Symptomatic patients usually PIZZ

• 25% of alpha1-antitrypsin deficiet adults >50 years have cirrhosis± HCC


Management:

• Supportive for emphysema and liver complications

• Quit smoking

• Augmentation therapy with human alpha1-antitrypsin if FEV1 < 80% predicted (expensive)

• ± liver transplant in decompensated cirrhosis