Neonatal Hemochromatosis

  • Materno-fetal/gestational alloimmune disorder (GALD): Antibody-mediated (type II) hypersensitivity.
  • Tendency to affect maternal half-siblings but not paternal half-siblings and recur in the subsequent pregnancies.
  • Multiple unaffected infants prior to having an affected infant (recurrence pattern defy genetic explanation).
  • Female survivors of NH have healthy unaffected infants.
  • Tissues (pancreas, salivary glands etc.) affected by siderosis express ZIP14, a known and an excess of circulating non-transferrin bound iron (NTBI) transporter.
  • Tissues (reticuloendothelial system) that are unaffected by siderosis express ferroportin, which permits iron export.
  • Associated with renal hypoplasia with dysgenesis of proximal tubules.
  • Needs multidisciplinary team effort for diagnosis and management.
  • Liver biopsy: Panlobular fibrosis in areas of hepatocyte dropout, degenerative and regenerative changes in the viable hepatocytes - feathery degeneration, multinucleation, pseudoacinar transformation and ductular metaplasia resembling ductal reaction, minimal inflammation, preservation/sparing of portal tracts by the disease process, diffuse intracytoplasmic hemosiderin accumulation in the viable hepatocytes, diffuse hepatocytic staining of complement membrane attack complex (C5b-9). Absence of the following: non-iron storage material in the hepatocytes, excess iron in Kupffer cells, viral cytopathy and in the viable hepatocytes and hemophagocytosis.
  • Prevention: Recommendation is that subsequent pregnancies be treated with 1 g/kg body weight (maximum 60 g) of IVIG at 14 weeks, 16 weeks, and then weekly from the 18th week of pregnancy until the end of gestation.
  • Treatment: First line: Double-volume exchange transfusion (to remove existing reactive antibody) followed immediately by administration of IVIG (1 g/kg) (to block antibody induced complement activation). Supportive medical therapy: Combination of antioxidants (vitamin E, selenium, and N-acetylcysteine), membrane stabilizers (prostaglandin E1), and iron chelators (deferoxamine).
  • Liver transplantation: When all the measures fail.
  • Prognosis: Generally poor. However, survival into adulthood is reported.

References

  • Feldman AG, Whitington PF. Neonatal hemochromatosis. J Clin Exp Hepatol. 2013;3:313-20.
  • Bonilla S, Prozialeck JD, Malladi P, et al. Neonatal iron overload and tissue siderosis due to gestational alloimmune liver disease. J Hepatol. 2012;56:1351-5.
  • Zoller H, Knisely AS. Control of iron metabolism--lessons from neonatal hemochromatosis. J Hepatol. 2012;56:1226-9.