ALPHA-1 ANTITRYPIN DEFICIENCY

Autosomal-recessive disorder

Pathogenesis

- Accumulation of 

α₁AT in endoplasmic reticulum leads to:
 * Autophagy

 * Mitochondrial dysfunction
 * Inflammation & hepatocyte damage .morphology
- Hepatocytes show (fatty change, hyaline cytoplasmic inclusions, Mallory bodies)

Clinical Features 

 - only 10%-15% of affected individuals have overt clinical features due to presence of:

  * Other genetic factors
  * Environmental factors
 - in neonates
  * Hepatitis & jaundice
 - in adolescence
  * Hepatitis>recovery, or>cirrhosis
 - in adults
  * Cirrhosis
  * Liver cell carcinoma in 2%-3%