Paediatrics: Alpha1-antitrypsin deficiency

Alpha₁-antitrypsin deficiency

Alpha₁-antitrypsin is a serum protease inhibitor responsible for controlling inflammatory cascades.

• It is the commonest genetic cause of liver disease in children, with autosomal dominant inheritance. Prevalence is 1:2000 to 1:7000.
• Genetic variants are identified by enzyme electrophoretic mobility as medium (M), slow (S), or very slow (Z). S is associated with 760% Alpha₁-antitrypsin level of normal; Z 715%. The normal genotype is designated PiMM. Only PiZZ individuals are at risk of liver disease.

Presentation

• Cholestasis in infancy may progress to liver failure.
• Cirrhosis can occur from late childhood to adulthood. Chronic liver disease affects 25% of patients in late adulthood.
• Pulmonary emphysema is the commonest presentation in adulthood.

Diagnosis

• Serum A₁-antitrypsin level d.
• Phenotyping by enzyme isoelectric focusing (see Alpha₁-antitrypsin deficiency).

Treatment

• Supportive treatment of liver complications.
• Strongly advise against smoking.
• Liver transplant for end-stage liver failure.