ABSTRACT
Homozygous PIZZ α1-antitrypsin deficiency, which has an incident of 1 in 1600 to 1
in 2000 live births, is the most common genetic cause of liver disease in children.
It is also associated with chronic liver disease and hepatocellular carcinoma in adults.
It is a well-known cause of pulmonary emphysema. Although emphysema is due to uninhibited
proteolytic destruction of the connective tissue backbone of the lung, liver disease
is thought to result from the toxic effects of the mutant α1 AT molecule retained within the endoplasmic reticulum of liver cells. Screening studies
done by Sveger in Sweden have shown that only 10 to 15% of the PIZZ population develop
clinically significant liver disease over the first 20 years of life. Recent studies
have suggested that a subgroup of PIZZ individuals are predisposed to liver injury
because of an inefficient degradation of mutant α1 ATZ within the endoplasmic reticulum. Altered migration of the abnormal α1 ATZ molecule in isoelectric focussing gels is the basis of the diagnosis of α1 AT deficiency. Treatment of α1 AT deficiency-associated liver disease is mostly supportive. Liver replacement therapy
has been used successfully for severe liver injury. An increasing number of patients
with severe emphysema have undergone lung transplantation.
KEY WORDS
a1 antitrypsin deficiency - metabolic liver disease - emphytsema - endoplasmic reticulum
retention
