Neonatal Hemochromatosis
Synonyms
2
Overview
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. 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. 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.
Symptoms
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).
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.
Diagnosis
Physical The physical examinatin in the nenatal perid is f little help but may reveal the fllwing: Placental edema IUGR Edema withut ascites liguria Disseminated intravascular cagulatin Jaundice in the first few days after birth Splenmegaly Pstmrtem examinatin reveals the fllwing: The liver is small, and the bile is stained. Cnturs may be irregular, and the strma may be cllapsed. Micrscpic examinatin f the liver reveals that the hepatcytes have giant cell transfrmatin with bile plugs r that the hepatcytes may nt be present at all. Als, the hepatcytes may shw sidersis. Scarring frm macrphages, which cntain high levels f stainable irn, may be present. Bile duct is prliferated. The spleen, lymph ndes, and bne marrw cntain minimal levels f stainable irn. Splenmegaly Pancreatic islet cell hyperplasia Absence f prximal renal tubules