33 - Neonatal hemochromatosis

Summary

Neonatal hemochromatosis (NH) is a heterogeneous group of disorders characterized by severe fetal or neonatal liver injury including cirrhosis, and hepatic and extrahepatic iron overload that occurs in a distribution similar to that of HFE hemochromatosis. Extensive liver injury and dysfunction are the dominant clinical features. Fetal loss or early neonatal death is usual, although some children survive. Despite its rarity, NH is one of the most commonly recognized causes of liver failure in neonates, has a high recurrence rate in sibships, and is a frequent indication for liver transplantation in the first 3 months of life. There is mounting evidence that many cases are caused by maternal alloimmunity against a fetal liver determinant. Treating at-risk mothers during pregnancy with intravenous IgG markedly decreases the risk and severity of NH in their subsequent offspring. Other NH cases are due to other acquired conditions of the mother, to intrauterine infection, or to rare heritable disorders of the fetus.

History

In 1956, Kiaer and Olesen described a Danish kinship in which six of nine sibs died in utero or as neonates of a disorder consistent with NH. In 1960, Fienberg reported two pairs of male siblings with “perinatal idiopathic hemochromatosis” and “giant cell hepatitis,” and suggested that this condition was caused by an “inborn error of metabolism.” In 1961, Laurendeau and colleagues described “idiopathic neonatal hemochromatosis” in two sisters.