The Neonatal Hemochromatosis Information Center

Medical Advisory Council

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The Neonatal Hemochromatosis Information Center

Medical Advisory Council:

 

Peter F. Whitington, MD

Sally Burnett Searle Professor of Pediatrics and Transplantation

Director, Organ Transplantation, Siragusa Transplantation Center, Ann & Robert H. Lurie Children’s Hospital of Chicago

Professor of Pediatrics and Medicine, Northwestern University Feinberg School of Medicine

T 312.227.4599 | F 312.227.9645 | pwhitington@luriechildrens.org | p-whitington@northwestern.edu

225 East Chicago Avenue, Box 57, Chicago, Illinois 60611-2605

and

Alex Knisely, MD
Consultant in Histopathology
Institute of Liver Studies
King's College Hospital
Denmark Hill
London  SE5 9RS  UK

These doctors have had a long term interest in neonatal hemochromatosis (NH) and have done much to help the small patients who are afflicted with this disease, as well as their families.  More information about them will follow on this web site. 

The following abstract is about Dr. Whitington, and some of his recent research:

High Dose Immunoglobulin During Pregnancy For Recurrent Neonatal Hemochromatosis

 Peter F. Whitington, MD

Department of Pediatrics

The Feinberg School of Medicine of Northwestern University

Children's Memorial Hospital

Chicago, IL

 

Judith U. Hibbard, MD

Department of Obstetrics and Gynecology

The Pritzker School of Medicine

The University of Chicago

Chicago, IL

Abstract

Background: Neonatal hemochromatosis (NH) is a rare disease of gestation that results in severe fetal liver injury. We hypothesized an alloimmune etiology for NH based on its high recurrence rate in sibships. In this study, we assessed the effectiveness of administering high-dose intravenous immunoglobulin derived from pooled serum of multiple donors (IV-Ig) during pregnancy to prevent or alter the severity of recurrent NH.

Study design: Women whose most recent pregnancy ended in documented NH were treated with IV-Ig, 1 g/kg body weight weekly from the 18th week until the end of gestation. The outcomes of treated pregnancies were compared to the outcomes of randomly selected previous affected pregnancies for each woman, which were used as historical controls.

Results: Fifteen women were treated through 16 pregnancies. All pregnancies progressed uneventfully and resulted in live babies with normal physical examinations and birth weights that were appropriate for gestational age. Twelve babies had evidence of liver involvement with NH: eleven had elevated serum a-fetoprotein and ferritin levels or elevated serum a-fetoprotein, including 4 with coagulopathy (INR > 1.5), and one had coagulopathy alone. All babies survived with medical or no treatment and are currently healthy. When analyzed on a per-mother basis comparing outcomes of treated gestations to randomly selected previous affected gestations, gestational IV-Ig therapy was associated with improved infant survival (p = 0·0009).

Conclusions: Treatment with high-dose IV-Ig during gestation appears to have modified recurrent NH so that it was not lethal to the fetus or newborn. These results further suggest an alloimmune mechanism for recurrent NH.

2-01-2005

Neonatal hemochromatosis (NH) is a rare gestational condition in which iron accumulates in the liver and extrahepatic sites of the fetus in a distribution similar to that seen in hereditary hemochromatosis.  It is usually lethal to the fetus or neonate. The risk of recurrence in subsequent offspring of a woman after the index case is greater than 80 percent. 

Dr. Whitington has hypothesized that recurrent NH is an immune-mediated (alloimmune) gestational disorder. Two research studies are in progress to study the immune mechanism of NH. 

Dr. Whitington designed a treatment to prevent recurrent lethal NH, wherein women with a history of having had their last pregnancy ending in documented NH were treated with intravenous immunoglobulin derived from pooled serum of multiple donors. All of the women treated on this protocol have given birth to live babies with normal physical examinations and birth weights that were appropriate for gestational age. Three-quarters of the babies have shown evidence of being affected with NH (similar to the predicted recurrence rate) and one-quarter have had liver injury severe enough to require medical treatment.  All babies have survived in good health.  These results strongly indicate that treatment with high-dose IV-Ig during gestation modified recurrent NH so that it was not lethal to the fetus or newborn.  These results were published in the November 6 2004 issue of the Lancet. (Whitington PF, Hibbard JU.  High dose immunoglobulin during pregnancy for recurrent neonatal haemochromatosis. Lancet 2004;364:1690-8).  This treatment protocol is open to women who have had a baby affected with NH and are pregnant or are anticipating pregnancy.  Interested persons should contact Dr. Whitington directly.

Dr. Whitington is seeking to identify the target of the immune attack responsible for NH.  He is using serum collected from affected women as a source of antibody to detect common fetal antigens that may be the antigen in question.  Preliminary results indicate that affected women’s serum contains antibodies that detect a 32kd protein expressed in fetal liver (both human and mouse) but not in mature liver.  If the results are confirmed, this fetal protein will be isolated and purified and ultimately used to develop an assay (ELISA) for detecting and quantifying antibody in the serum of women at risk.  Being able to measure antibody will permit refinement of the treatment protocol.  Affected women are invited to participate in these studies and should contact Dr. Whitington if interested through the following contact information:

Peter F. Whitington, MD

Sally Burnett Searle Professor of Pediatrics and Transplantation

Director, Organ Transplantation, Siragusa Transplantation Center, Ann & Robert H. Lurie Children’s Hospital of Chicago

Professor of Pediatrics and Medicine, Northwestern University Feinberg School of Medicine

T 312.227.4599 | F 312.227.9645 | pwhitington@luriechildrens.org | p-whitington@northwestern.edu

225 East Chicago Avenue, Box 57, Chicago, Illinois 60611-2605



 

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