Abstracto

Unique case of alpha 1-antitrypsin deficiency causing decreased protein C and S activity leading to DVT and pulmonary embolism.

Manoj S

Although alpha-1 antitrypsin deficiency (AATD) is generally considered to be rare, estimates that 80,000 to 100,000 individuals in the United States have severe deficiency of AAT suggest that the disease is under-recognized. The prevalence of AAT varies considerably from one country to another; however, it is estimated that more than 3 million people worldwide have allele combinations associated with severe deficiency of AAT. The pathogenesis of the liver disease is quite different and is called a "toxic gain of function." The liver disease results from the accumulation within the hepatocyte of un-secreted variant AAT protein. Only those genotypes associated with pathologic polymerization of AAT within the endoplasmic reticulum of hepatocytes (e.g., PI*ZZ type AATD) produce disease. Most patients with liver disease due to AATD are homozygous for the Z allele (i.e., PI*ZZ); liver disease does not occur in null homozygotes who have severe deficiency of AAT, but no intra-hepatocytic accumulation.