Heterozygous M3Mmalton alpha(1)-antitrypsin deficiency associated with end-stage liver disease: Case report and review

alpha (1)-Antitrypsin (alpha 1AT) deficiency is an autosomal recessive diso rder that can cause pulmonary emphysema and liver disease. We report here t he case of a 59-year-old woman who was admitted to hospital for evaluation of jaundice. She had no history of hepatitis or childhood liver disease. Sh e had never received a blood transfusion, nor had she abused drugs or alcoh ol. Transjugular liver biopsy was then performed and revealed a micronodula r cirrhosis. Ten months later, because of persistent liver cell failure and ascites, she underwent an orthotopic liver transplantation. Investigation of a1AT system in the proband revealed a substantial decrease in serum alph a 1AT associated with a low elastase inhibitory capacity. The Pi phenotype revealed a PiM-like profile. Sequencing of exons 1-5 demonstrated the prese nce of the M3 allele. Moreover, a triple nucleotide deletion was detected i n exon 2 of one allele. This caused an "in-phase" frameshift, coding for a protein deficient in a single Phe residue, which corresponded to the Mmalto n variant. After liver biopsy, periodic acid-Schiff-positive acidophilic bo dies resistant to diastase digestion were observed in the cytoplasm of hepa tocytes. These results demonstrated that our patient had a heterozygous M3M malton a1AT genotype related to a deficiency phenotype. This observation is the first of a patient with heterozygous Mmalton genotype associated with an a1AT deficiency that induced severe liver disease requiring orthotopic l iver transplantation. (C) 2001 American Association for Clinical Chemistry.