Neonatal hemochromatosis

Neonatal hemochromatosis (NH), also known as gestational alloimmune liver disease (GALD), is a severe condition characterized by massive iron overload in the liver and other organs, presenting at birth or within the first few days of life. It is the most common identifiable cause of neonatal acute liver failure. The disease is now understood to result primarily from a maternal alloimmune mechanism in which maternal antibodies cross the placenta and target the fetal liver, causing complement-mediated hepatocyte injury and subsequent abnormal iron deposition. This distinguishes it from hereditary hemochromatosis seen in adults. The condition predominantly affects the liver, leading to severe hepatic dysfunction or liver failure, but iron accumulation also occurs in extrahepatic sites including the heart, pancreas, thyroid, and salivary glands — notably sparing the reticuloendothelial system (spleen and bone marrow). Key clinical features include intrauterine growth restriction, oligohydramnios or polyhydramnios, prematurity, severe jaundice, coagulopathy, hypoglycemia, hypoalbuminemia, edema, and ascites. Many affected infants present with fulminant liver failure shortly after birth. Without treatment, neonatal hemochromatosis carries a very high mortality rate. The current treatment landscape has been transformed by two key interventions. Exchange transfusion combined with intravenous immunoglobulin (IVIG) has significantly improved survival by removing circulating maternal antibodies and blocking complement activation. Liver transplantation remains an option for infants who do not respond to medical therapy. Importantly, recurrence in subsequent pregnancies is very high (approximately 80-90%), but antenatal administration of high-dose IVIG to the mother during pregnancy has proven highly effective in preventing the disease in subsequent gestations.

Common questions about Neonatal hemochromatosis