?1-antitrysin deficiency

• ?1-antitrysin is a serine protease inhibitor involved in controlling inflammatory cascades (deficiency of this family are called serpinopathies)
• It is synthesized in the liver
• Protects from tissue damage by neutrophil elastase
• It is the chief genetic cause of liver disease in children
• In adults it causes;
  • Emphysema
  • Chronic liver disease
  • HCC
• It is autosomal recessive, mutation is on Chromosome 14 – carrier frequency is 1 in 10
• Genetic variants are typed by electrophoretic mobility as medium (M), slow (S) and very slow (ZZ)

Clinical features

• PiZZ genotype
• Dyspnoea from emphysema
• Cirrhosis
• Cholestatic jaundice

Tests

• Reduced levels of ?1-antitrysin
• Liver biopsy
• Prenatal diagnosis via CVS
• CT

Management

• Mostly supportive for emphysema and liver complications
• Quit smoking
• Consider augmentation therapy with ?1-antitrysin pooled from human plasma
• Liver transplantation

Prognosis

• Worse if male and obese
• Emphysema is most commonly the cause of death (liver disease in 5%)