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] and can be thought of as a form of fulminant hepatic failure.
Treatment after birth requires supportive care with or without administration of an iron-chelating cocktail and several antioxidants. Survival rates in babies who undergo liver transplantation is reportedly 50%. [3] Exchange transfusions and intravenous immunoglobulins have emerged as possible new treatments. [4, 5] Liver disease ascribed to hemosiderosis has not recurred in survivors to date.
The prognosis is extremely poor. Some infants recover with supportive care, but this rarely occurs.
Suggest genetic counseling if the parents of a child with neonatal hemochromatosis desire to have another child. However, genetic patterns are unclear.
Go to Hemochromatosis and Dermatologic Manifestations of Hemochromatosis for complete information on these topics.
Pathophysiology
In hemochromatosis, hepatocytes are the first site of iron deposition. Liver tissue of affected infants displays severe injury with marked loss of hepatocytes. Involvement then extends to 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 restriction (IUGR).
Postmortem examination reveals the following:
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The liver is small and bile stained; contours may be irregular, and the stroma may be collapsed
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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. Cirrhosis may be present
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Bile ducts are proliferated
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The spleen, lymph nodes, and bone marrow contain minimal levels of stainable iron
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Splenomegaly, pancreatic islet cell hyperplasia, and absence of proximal renal tubules is noted
Etiology
The exact cause of neonatal hemochromatosis is unknown. There are two schools of thought: one 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.
Four pieces of evidence suggest that neonatal hemochromatosis may be due to an acquired and persistent maternal factor. First, neonatal hemochromatosis recurs within sibships at a rate higher than expected for disorders transmitted in an autosomal recessive manner. Second, several kindreds are known in which mothers have given birth to children with neonatal hemochromatosis who were fathered by different men.
Third, several kindreds are known in which parents of children with neonatal hemochromatosis had histories of exposure to blood with or without clinical hepatitis. Fourth, 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.
These 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.
Epidemiology
Neonatal hemochromatosis is rare. [6] 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%. It has been described variously as a dominant and a recessive disorder. [7]
Neonatal hemochromatosis has been documented in Filipino, African American, Hong Kong Chinese, and white infants. No reported increase rates in any race are noted to date. No sex predilection is known. Neonatal hemochromatosis is thought to occur with damage to the liver at 16-30 weeks' gestation. [8]
