Neonatal Hemochromatosis: Is It an Alloimmune Disease?

Abstract

Neonatal hemochromatosis (NH) has been defined clinically as severe neonatal liver disease in association with extrahepatic siderosis in a distribution similar to that seen in HFE-associated hereditary hemochromatosis (1). Though it is generally considered a rare disease, it is one of the most commonly recognized causes of liver failure in the neonate and a frequent indication for liver transplantation in the first 3 months of life (2–4). Its etiology and pathogenesis are as yet unknown. Indeed, it has been considered to be a syndrome in which a number of primary etiologies, such as infection, genetic-metabolic disease and toxic insult, lead to a common phenotype. We have hypothesized that much, if not all, NH is a consequence of gestational alloimmune disease. This review presents the clinical evidence leading to this hypothesis, the data we have collected in its support, and the direction our investigations are taking to ultimately prove or disprove it.