eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Hemochromatosis, Neonatal

Author: Roland L Boyd, DO, FAAP, FACOP, Neonatologist, Section of Neonatology, Neonatal Services Limited
Coauthor(s): Jatinder Bhatia, MBBS, Professor of Pediatrics, Chief, Section of Neonatology, Department of Pediatrics, Medical College of Georgia; Joseph H Clark, MD, Professor, Department of Pediatric, Division of Gastroenterology, Medical College of Georgia
Contributor Information and Disclosures

Updated: Mar 6, 2008

Introduction

Background

Neonatal hemochromatosis is a syndrome in which severe liver disease of fetal or perinatal onset is associated with deposition of stainable iron in extrahepatic sites.¹ The distribution of extrahepatic iron mimics that observed in hepatic iron (HFE) disease, the most common form of hemochromatosis known in Europe and the Americas, and liver disease is common in late-stage HFE disease. Nonetheless, neonatal hemochromatosis is not a manifestation of HFE disease. Neonatal hemochromatosis is not a single disorder but is a syndrome with an unclear etiology. Neonatal hemochromatosis represents disordered iron handling due to injury to the perinatal liver.² Neonatal hemochromatosis can be thought of as a form of fulminant hepatic failure.

Four pieces of evidence suggest that neonatal hemochromatosis may be due to an acquired and persistent maternal factor. (1) Neonatal hemochromatosis recurs within sibships at a rate higher than expected for disorders transmitted in an autosomal recessive manner. (2) Several kindreds are known in which mothers have given birth to children with neonatal hemochromatosis who were fathered by different men. (3) Several kindreds are known in which parents of children with neonatal hemochromatosis had histories of exposure to blood with or without clinical hepatitis. (4) Anecdotal evidence suggests that administering intravenous immunoglobulin during pregnancy in a woman who has already had an infant with neonatal hemochromatosis leads to a relatively favorable outcome.

This data suggest mitochondrial disease; transplacental transmission of an infective, possibly viral, agent; or transplacental transmission of an antibody as a cause of at least some instances of neonatal hemochromatosis. Because neonatal hemochromatosis is a syndrome, any of these possibilities may be correct in a given family, and all of them must be considered.

Treatment after birth requires supportive care with or without administration of an iron-chelating cocktail and several antioxidants. Liver transplantation has saved some babies. Liver disease ascribed to siderosis has not recurred in survivors to date.

Pathophysiology

In hemochromatosis, hepatocytes are the first site of iron deposition. This then extends to involve the hepatic lobule and the pancreatic parenchyma. The myocardial and endocrine systems may also be involved, which can lead to failure of both. The effects can be observed antenatally with involvement of the placenta, causing placental edema and oligohydramnios. These infants may be stillborn, premature, or have intrauterine growth retardation (IUGR).

Frequency

United States

Neonatal hemochromatosis is rare.³ To date, no rates of this disease are reported. Studies suggest a genetic prevalence of 0.03-0.038 or a heterozygosity prevalence of 6-7%.

Mortality/Morbidity

The prognosis is extremely poor. Some infants recover with supportive care, but this rarely occurs. Survival is documented in patients who have received liver transplantation.

Race

Neonatal hemochromatosis has been documented in Filipino, African American, Hong Kong Chinese, and Caucasian infants. No reported increase rates in any race are noted to date.

Sex

No sex predilection is known.

Age

Neonatal hemochromatosis is thought to occur with damage to the liver at 16-30 weeks' gestation.

Clinical

History

Clues that the patient has or does not have neonatal hemochromatosis may not be present. Clues in pregnancy may indicate the diagnosis of neonatal hemochromatosis, but they are nonspecific.

• Oligohydramnios is frequently observed.
• Polyhydramnios is less commonly observed.
• Suspect neonatal hemochromatosis if the infant develops liver disease and all other metabolic, infectious, and hemorrhagic causes are eliminated.
• Decreased fetal movement has been reported.
• Forty percent of infants born with neonatal hemochromatosis are premature.
• IUGR occurs in 25% of infants with neonatal hemochromatosis.

Physical

• The physical examination in the neonatal period is of little help but may reveal the following:
  • Placental edema
  • IUGR
  • Edema without ascites
  • Oliguria
  • Disseminated intravascular coagulation
  • Jaundice in the first few days after birth
  • Splenomegaly
• Postmortem examination reveals the following:
  • The liver is small, and the bile is stained. Contours may be irregular, and the stroma may be collapsed.
  • Microscopic examination of the liver reveals that the hepatocytes have giant cell transformation with bile plugs or that the hepatocytes may not be present at all. Also, the hepatocytes may show siderosis. Scarring from macrophages, which contain high levels of stainable iron, may be present.
  • Bile duct is proliferated.
  • The spleen, lymph nodes, and bone marrow contain minimal levels of stainable iron.
• Splenomegaly
  • Pancreatic islet cell hyperplasia
  • Absence of proximal renal tubules

Causes

The exact cause of neonatal hemochromatosis remains a mystery. The following are two schools of thought:

• The first hypothesizes that injury to the liver causes abnormal handling of iron by the liver.
• The other hypothesizes that the abnormal handling of iron by the liver leads to liver injury and failure.

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