Mutations Can Mimic Neonatal Hemochromatosis.

Neonatal hemochromatosis (NH), one of the most common causes of liver failure in the neonate, often causes fetal loss or death during the neonatal period. Most cases are thought to be due to gestational alloimmune disease; however, other rare causes have been reported. NH is generally considered congenital and familial but not heritable. We present an infant diagnosed with NH whose clinical course differed significantly from that of most NH cases: at 11 months of age he had normal levels of liver enzymes, ferritin, and bilirubin, and normal neurodevelopment. This term male infant was born with a history of intrauterine growth restriction, oligohydramnios, and pericardial effusion. On day of life 1, he had hyperbilirubinemia and transaminitis; on day of life 3, ferritin was elevated; and on day of life 9, an MRI revealed iron deposits in the liver and renal cortex. Phenotypic features prompted a genetics consult. Whole-exome sequencing revealed a variant in the phosphatidylinositol glycan biosynthesis class A protein () gene. Germ-line mutations are generally thought to be lethal in utero; however, there are reports of infants with mutations associated with dysmorphic features, neurologic manifestations, biochemical perturbations, and systemic iron overload; development can be normal up to 6 months of age. Because of the differences between infants with NH versus germ-line mutations in inheritance, prognosis, and natural history of disease, we propose that gene testing should be considered when evaluating newborns who present with NH.