Paediatrics: Alpha1-antitrypsin deficiency

Alpha₁-antitrypsin deficiency

Alpha₁-antitrypsin is a serum protease inhibitor responsible for control-ling 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%. 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 in late childhood to adult. 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.