Neonatal iron overload and tissue siderosis due to gestational alloimmune liver disease

Neonatal Hemochromatosis

“…Liver tissue of infants with GALD-NH displays severe injury with marked loss of hepatocytes (often less than 10% of normal newborn liver). 15,16 In some cases, no hepatocytes remain. 17 Surviving hepatocytes show siderosis, giant-cell or pseudoacinar transformation, and canalicular bile plugs.…”

“…12,15,19,20 In a recent cohort of 33 fetuses with NH, thyroid siderosis was more frequent than pancreatic. 14 Less frequently affected are the gastric glands, Brunner glands, parathyroid glands, thymus (Hassall corpuscles), renal tubules, pancreatic islets, adenohypophysis, and chondrocytes in hyaline cartilage.…”

“…In fetuses with GALD, liver injury results in significantly decreased production of hepcidin. 15 As a result, there is less negative feedback on ferroportin and excess iron is transported from the placenta to the fetal liver. In addition, transferrin gene expression is decreased, resulting in reduced iron binding capacity.…”

“…Tissues affected by siderosis express ZIP14, a known NTBI transporter. 15 However, several tissues that express ZIP14 do not develop siderosis in GALD. Tissues that are unaffected by siderosis express ferroportin, which permits iron export.…”

“…2,7 Iron studies reveal high serum ferritin levels (>800 ng/mL), low transferrin levels and high iron saturations. 15 Serum ferritin levels are a sensitive indicator for NH but are not specific as many liver diseases will show similar elevations.…”