Genetic hemochromatosis (GH) and alpha-1 antitrypsin (AAT) deficiency (AATD) are two autosomal recessive disorders associated with an increased risk for liver injury. Among different AATD and GH genotypes, the M-Malton and the S variants are frequent in Sardinia, an Italian island of the Mediterranean Sea, suggesting that a possible relationship between these two metabolic disorders in chronic liver diseases should be considered. Here we report a case of liver cirrhosis associated with double heterozygosity for M-Malton AATD and H63D GH alleles. The histological observation revealed micronodular cirrhosis with focal micro-and macrovesicular steatosis with globules of AAT protein and iron overload. The clinical and laboratory picture led to listing the patient for orthotopic liver transplantation. Two sons, who were apparently healthy, on molecular testing showed a normal AAT genotype, whereas one of them was heterozygous for the H63D GH mutation. This clinical case underlines the importance of the diagnostic role played by the liver biopsy, in particular when rare genetic variants could be involved.
Liver cirrhosis associated with double heterozygosity for genetic hemochromatosis (H63D) and alpha-1 antitrypsin deficiency (M-Malton) – A case report
Faa G.;Pichiri G.;Coni S.;Annunziata A.;Fiorentino G.;
2026-01-01
Abstract
Genetic hemochromatosis (GH) and alpha-1 antitrypsin (AAT) deficiency (AATD) are two autosomal recessive disorders associated with an increased risk for liver injury. Among different AATD and GH genotypes, the M-Malton and the S variants are frequent in Sardinia, an Italian island of the Mediterranean Sea, suggesting that a possible relationship between these two metabolic disorders in chronic liver diseases should be considered. Here we report a case of liver cirrhosis associated with double heterozygosity for M-Malton AATD and H63D GH alleles. The histological observation revealed micronodular cirrhosis with focal micro-and macrovesicular steatosis with globules of AAT protein and iron overload. The clinical and laboratory picture led to listing the patient for orthotopic liver transplantation. Two sons, who were apparently healthy, on molecular testing showed a normal AAT genotype, whereas one of them was heterozygous for the H63D GH mutation. This clinical case underlines the importance of the diagnostic role played by the liver biopsy, in particular when rare genetic variants could be involved.
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