Heterozygous M3Mmalton alpha1-antitrypsin deficiency associated with end-stage liver disease: case report and review.
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.
Canva
V
V
Department of Hepatology and Gastroenterology, Hôpital C. Huriez, CHRU-Lille, 59037 Lille Cedex, France. vcanva@chru-lille.fr
Piotte
S
S
Aubert
J P
JP
Porchet
N
N
Lecomte-Houcke
M
M
Huet
G
G
Zenjari
T
T
Roumilhac
D
D
Pruvot
F R
FR
Degand
P
P
Paris
J C
JC
Balduyck
M
M
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
D000515:alpha 1-Antitrypsin