Neonatal hemochromatosis and gestational alloimmune liver disease

Abstract

Neonatal hemochromatosis (NH) is defined as severe neonatal liver disease in association with siderosis of extrahepatic tissues. It is the phenotypic consequence of severe fetal liver disease. Gestational Alloimmune Liver Disease (GALD) is the cause of fetal liver injury leading to nearly all cases of NH. The mechanism of GALD involves maternal IgG alloantibodies directed against a fetal hepatocyte antigen. Fetal complement is bound and the terminal complement cascade is activated, resulting in formation of membrane attack complex and hepatocyte injury and death. In addition to causing chronic liver injury and the NH phenotype, GALD can also cause acute liver failure in the fetus and newborn, often in the absence siderosis. Identification of GALD as the common cause of NH has led to better mechanistic understanding of NH and to a more focused diagnostic approach. Addressing the immune mechanism has led to improved treatment of affected newborns. Treatment during gestation is effective in preventing recurrent GALD.