Abstract
A deficiency of the serum protease inhibitor, α1-antitrypsin (AAT), is frequently associated with chronic obstructive lung disease in adult years. About 17% of individuals with the deficiency (PI type ZZ) develop evidence of liver abnormalities in the early months, and a portion of these proceed to cirrhosis. Prenatal diagnosis has previously been available by PI typing of a fetal blood sample, or by using synthetic oligonucleotide probes specific for M and Z AAT, on cultured amniocytes, although technical difficulties have been encountered with use of the latter. We have used a genomic probe (provided by Dr. S. Woo) on DNA digested with the restriction enzyme AvaII. We have found a pattern of DNA fragments unique to the PI Z allele found with 58/58 Z alleles and 0/47 non-Z, i.e. M or S, alleles. Reliable prenatal diagnosis can be carried out using only 2 μg. of DNA from non-cultured amniocytes or from chorion villus biopsies.
We have followed 25 children with AAT deficiency to 4 or more years of age (maximum 20 years) and have found that at least 65% appear to have a resolution of their liver abnormalities, while the remainder develop progressive liver disease and cirrhosis. We and others have found that the course of disease in PI ZZ sibs is frequently different within families. Sibs born after a child whose liver disease has resolved probably have about a 5-10% risk for developing severe liver disease. There are only a few reported families in which sibs have been born after a child with severe liver disease. The risk for severe liver disease in a subsequent child may be as high as 30% in these families.
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Cox, D., Mansfield, T. & Bech-Hansen, T. 813 PRENATAL DIAGNOSIS AND GENETIC RISK IN ALPHA1 ANTITRYPSIN DEFICIENCY PI TYPE ZZ. Pediatr Res 19, 246 (1985). https://doi.org/10.1203/00006450-198504000-00843
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DOI: https://doi.org/10.1203/00006450-198504000-00843