Abstract

Alpha 1 antitrypsin deficiency is one of the most common metabolic disorders, frequently associated with obstructive lung disease and occasionally with childhood liver cirrhosis. Prenatal diagnosis of this deficiency has been accomplished using a DNA polymorphism detected by the restriction enzyme AvaII. A unique haplotype of DNA fragments is observed in deficient (PI type ZZ) subjects. Diagnosis is therefore possible directly from fetal tissue, unlike other prenatal diagnoses using linkage of a DNA polymorphism within a specific family. This approach must be modified for rare deficiency alleles of alpha 1 antitrypsin (PI* Mmalton, PI* Mdurate, and PI*QO or null). Knowledge of risk of severe disease in the fetus is important for the application of prenatal diagnosis. From the limited data available to date, the risk for a given PI ZZ fetus to develop severe liver disease has been estimated at 13% where a previous PI ZZ sib had no liver disease or liver disease which resolved during early childhood, and a risk of 40% where a previous PI ZZ sib had developed severe liver disease.