N-Acetyltransferase (NAT) participates in detoxification reactions of compounds with arylamine and hydrazine moieties as well as in activation pathways of occupational and environmental pollutants with mutagenic and carcinogenic potential. There are three NAT gene loci (NAT1, NAT2, NAT3) and the NAT2 gene locus (chromosome 8) has 4 alleles (M1, M2, M3, and M4). Any mutant NAT2 allele or 2 heterozygous defective alleles cause the slow acetylator phenotype. We hypothesized that if liver failure in children withα 1 antitrypsin deficiency (AATD) is toxin exposure related then these children would have a lesser or greater than expected NAT2 mutant rate compared to children with biliary atresia (BA) or neonatal hepatitis (NH) induced liver failure.

Methods DNA was isolated from the Childrens Hospital of Pittsburgh liver bank from children who required liver transplantation for AATD (n = 30), BA (n = 66), and NH (n = 22); and 43 control donor splenocyte specimens. NAT2 genotype analysis was done using PCR-RFLP to determine mutations in M1, M2, M3, and M4 (Bell et al. Carcinogenesis 14,1689-1693, 1993).

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