title: Heterozygous M3Mmalton alpha1-antitrypsin deficiency associated with end-stage liver disease: case report and review.
abstract: Alpha1-antitrypsin (alpha1AT) deficiency is an autosomal recessive disorder that can cause pulmonary emphysema and liver disease. We report here the 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. She had never received a blood transfusion, nor had she abused drugs or alcohol. Transjugular liver biopsy was then performed and revealed a micronodular cirrhosis. Ten months later, because of persistent liver cell failure and ascites, she underwent an orthotopic liver transplantation. Investigation of alpha1AT system in the proband revealed a substantial decrease in serum alpha1AT associated with a low elastase inhibitory capacity. The Pi phenotype revealed a PiM-like profile. Sequencing of exons 1-5 demonstrated the presence of the M3 allele. Moreover, a triple nucleotide deletion was detected in 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 Mmalton variant. After liver biopsy, periodic acid-Schiff-positive acidophilic bodies resistant to diastase digestion were observed in the cytoplasm of hepatocytes. These results demonstrated that our patient had a heterozygous M3Mmalton alpha1AT genotype related to a deficiency phenotype. This observation is the first of a patient with heterozygous Mmalton genotype associated with an alpha1AT deficiency that induced severe liver disease requiring orthotopic liver transplantation.
authors.affiliation: Department of Hepatology and Gastroenterology, Hôpital C. Huriez, CHRU-Lille, 59037 Lille Cedex, France. vcanva@chru-lille.fr
authors.forename: V
authors.initials: V
authors.lastname: Canva
authors.forename: S
authors.initials: S
authors.lastname: Piotte
authors.forename: J P
authors.initials: JP
authors.lastname: Aubert
authors.forename: N
authors.initials: N
authors.lastname: Porchet
authors.forename: M
authors.initials: M
authors.lastname: Lecomte-Houcke
authors.forename: G
authors.initials: G
authors.lastname: Huet
authors.forename: T
authors.initials: T
authors.lastname: Zenjari
authors.forename: D
authors.initials: D
authors.lastname: Roumilhac
authors.forename: F R
authors.initials: FR
authors.lastname: Pruvot
authors.forename: P
authors.initials: P
authors.lastname: Degand
authors.forename: J C
authors.initials: JC
authors.lastname: Paris
authors.forename: M
authors.initials: M
authors.lastname: Balduyck
mesh_terms: D005260:Female; D006579:Heterozygote; D006651:Histocytochemistry; D006801:Humans; D008099:Liver / Q000473:pathology; D017093:Liver Failure / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016031:Liver Transplantation; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D000515:alpha 1-Antitrypsin / Q000235:genetics* / Q000378:metabolism
chemical_list: D000515:alpha 1-Antitrypsin