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

Silvana Bonilla, Joshua Daniel Prozialeck, Padmini Malladi, Xiaomin Pan, Songtao Yu, Hector Melin-Aldana, Peter F Whitington*

*Corresponding author for this work

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background & Aims: Gestational alloimmune liver disease is the main cause of the neonatal hemochromatosis phenotype, wherein severe neonatal liver disease is associated with iron overload and extrahepatic tissue siderosis. How fetal liver disease produces extrahepatic siderosis is not known. We hypothesized that fetal liver injury causes deficient hepcidin production and poor regulation of placental iron flux. Under the resulting conditions of iron overload, the tissue pattern of extrahepatic siderosis is determined by the normal expression of proteins involved in the import of non-transferrin-bound iron and the export of cellular iron. Methods: Liver and extrahepatic tissues from infants with gestational alloimmune liver disease were examined and compared to normal age-appropriate tissues. Results: Serum iron indices indicate iron overload and excess non-transferrin bound iron in gestational alloimmune liver disease. The diseased liver showed significantly reduced hepcidin, hemojuvulin, and transferrin gene expression compared to the normal fetal and neonatal liver. Those extrahepatic tissues that are typically involved in pathological siderosis in neonatal hemochromatosis, whether from normal or diseased newborns, consistently expressed solute carrier family 39 (zinc transporter), member 14 (ZIP14) for non-transferrin-bound iron uptake and expressed little ferroportin for iron export. Conclusions: Excess non-transferrin-bound iron in gestational alloimmune liver disease may result from fetal liver injury that causes reduced synthesis of key iron regulatory and transport proteins. Whereas, the pattern of extrahepatic siderosis appears to be determined by the normal capacity of various tissues to import non-transferrin-bound iron and not export cellular iron.

Original languageEnglish (US)
Pages (from-to)1351-1355
Number of pages5
JournalJournal of Hepatology
Volume56
Issue number6
DOIs
StatePublished - Jun 1 2012

Fingerprint

Siderosis
Iron Overload
Liver Diseases
Iron
Hepcidins
Liver
Infant, Newborn, Diseases
Iron-Regulatory Proteins
Fetal Diseases
Wounds and Injuries
Transferrin
Carrier Proteins

Keywords

  • Extrahepatic siderosis
  • Ferroportin
  • Neonatal hemochromatosis
  • Non-transferrin-bound iron
  • ZIP14

ASJC Scopus subject areas

  • Hepatology

Cite this

@article{6f008b6ab16b4d5a8fda8908c503a2ef,
title = "Neonatal iron overload and tissue siderosis due to gestational alloimmune liver disease",
abstract = "Background & Aims: Gestational alloimmune liver disease is the main cause of the neonatal hemochromatosis phenotype, wherein severe neonatal liver disease is associated with iron overload and extrahepatic tissue siderosis. How fetal liver disease produces extrahepatic siderosis is not known. We hypothesized that fetal liver injury causes deficient hepcidin production and poor regulation of placental iron flux. Under the resulting conditions of iron overload, the tissue pattern of extrahepatic siderosis is determined by the normal expression of proteins involved in the import of non-transferrin-bound iron and the export of cellular iron. Methods: Liver and extrahepatic tissues from infants with gestational alloimmune liver disease were examined and compared to normal age-appropriate tissues. Results: Serum iron indices indicate iron overload and excess non-transferrin bound iron in gestational alloimmune liver disease. The diseased liver showed significantly reduced hepcidin, hemojuvulin, and transferrin gene expression compared to the normal fetal and neonatal liver. Those extrahepatic tissues that are typically involved in pathological siderosis in neonatal hemochromatosis, whether from normal or diseased newborns, consistently expressed solute carrier family 39 (zinc transporter), member 14 (ZIP14) for non-transferrin-bound iron uptake and expressed little ferroportin for iron export. Conclusions: Excess non-transferrin-bound iron in gestational alloimmune liver disease may result from fetal liver injury that causes reduced synthesis of key iron regulatory and transport proteins. Whereas, the pattern of extrahepatic siderosis appears to be determined by the normal capacity of various tissues to import non-transferrin-bound iron and not export cellular iron.",
keywords = "Extrahepatic siderosis, Ferroportin, Neonatal hemochromatosis, Non-transferrin-bound iron, ZIP14",
author = "Silvana Bonilla and Prozialeck, {Joshua Daniel} and Padmini Malladi and Xiaomin Pan and Songtao Yu and Hector Melin-Aldana and Whitington, {Peter F}",
year = "2012",
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Neonatal iron overload and tissue siderosis due to gestational alloimmune liver disease. / Bonilla, Silvana; Prozialeck, Joshua Daniel; Malladi, Padmini; Pan, Xiaomin; Yu, Songtao; Melin-Aldana, Hector; Whitington, Peter F.

In: Journal of Hepatology, Vol. 56, No. 6, 01.06.2012, p. 1351-1355.

Research output: Contribution to journalArticle

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T1 - Neonatal iron overload and tissue siderosis due to gestational alloimmune liver disease

AU - Bonilla, Silvana

AU - Prozialeck, Joshua Daniel

AU - Malladi, Padmini

AU - Pan, Xiaomin

AU - Yu, Songtao

AU - Melin-Aldana, Hector

AU - Whitington, Peter F

PY - 2012/6/1

Y1 - 2012/6/1

N2 - Background & Aims: Gestational alloimmune liver disease is the main cause of the neonatal hemochromatosis phenotype, wherein severe neonatal liver disease is associated with iron overload and extrahepatic tissue siderosis. How fetal liver disease produces extrahepatic siderosis is not known. We hypothesized that fetal liver injury causes deficient hepcidin production and poor regulation of placental iron flux. Under the resulting conditions of iron overload, the tissue pattern of extrahepatic siderosis is determined by the normal expression of proteins involved in the import of non-transferrin-bound iron and the export of cellular iron. Methods: Liver and extrahepatic tissues from infants with gestational alloimmune liver disease were examined and compared to normal age-appropriate tissues. Results: Serum iron indices indicate iron overload and excess non-transferrin bound iron in gestational alloimmune liver disease. The diseased liver showed significantly reduced hepcidin, hemojuvulin, and transferrin gene expression compared to the normal fetal and neonatal liver. Those extrahepatic tissues that are typically involved in pathological siderosis in neonatal hemochromatosis, whether from normal or diseased newborns, consistently expressed solute carrier family 39 (zinc transporter), member 14 (ZIP14) for non-transferrin-bound iron uptake and expressed little ferroportin for iron export. Conclusions: Excess non-transferrin-bound iron in gestational alloimmune liver disease may result from fetal liver injury that causes reduced synthesis of key iron regulatory and transport proteins. Whereas, the pattern of extrahepatic siderosis appears to be determined by the normal capacity of various tissues to import non-transferrin-bound iron and not export cellular iron.

AB - Background & Aims: Gestational alloimmune liver disease is the main cause of the neonatal hemochromatosis phenotype, wherein severe neonatal liver disease is associated with iron overload and extrahepatic tissue siderosis. How fetal liver disease produces extrahepatic siderosis is not known. We hypothesized that fetal liver injury causes deficient hepcidin production and poor regulation of placental iron flux. Under the resulting conditions of iron overload, the tissue pattern of extrahepatic siderosis is determined by the normal expression of proteins involved in the import of non-transferrin-bound iron and the export of cellular iron. Methods: Liver and extrahepatic tissues from infants with gestational alloimmune liver disease were examined and compared to normal age-appropriate tissues. Results: Serum iron indices indicate iron overload and excess non-transferrin bound iron in gestational alloimmune liver disease. The diseased liver showed significantly reduced hepcidin, hemojuvulin, and transferrin gene expression compared to the normal fetal and neonatal liver. Those extrahepatic tissues that are typically involved in pathological siderosis in neonatal hemochromatosis, whether from normal or diseased newborns, consistently expressed solute carrier family 39 (zinc transporter), member 14 (ZIP14) for non-transferrin-bound iron uptake and expressed little ferroportin for iron export. Conclusions: Excess non-transferrin-bound iron in gestational alloimmune liver disease may result from fetal liver injury that causes reduced synthesis of key iron regulatory and transport proteins. Whereas, the pattern of extrahepatic siderosis appears to be determined by the normal capacity of various tissues to import non-transferrin-bound iron and not export cellular iron.

KW - Extrahepatic siderosis

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KW - Non-transferrin-bound iron

KW - ZIP14

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