A Newborn Girl with Hyperbilirubinemia

Posted by • June 26th, 2015

In the latest Case Record of the Massachusetts General Hospital, a newborn girl was transferred to this hospital because of hypotension, coagulopathy, anemia, and hyperbilirubinemia. Generalized edema, anuria, and respiratory distress developed, and the trachea was intubated. Diagnostic procedures were performed.

Neonatal hemochromatosis is the most common cause of neonatal liver failure and the leading indication for liver transplantation in infants. It is characterized by progressive iron deposition during the fetal period, predominantly targeting the liver, pancreas, heart, and thyroid and salivary glands but sparing the reticuloendothelial system.

Clinical Pearls

Is neonatal hemochromatosis a genetic disease?

Neonatal hemochromatosis was considered for decades to be part of the hemochromatosis family and to have a genetic cause. Despite multiple attempts, no candidate genes were identified. Also known as gestational alloimmune liver disease, neonatal hemochromatosis is now recognized to be a congenital alloimmune hepatitis and is defined as the association of severe neonatal liver disease with iron deposition (siderosis) in extrahepatic tissue. Neonatal hemochromatosis is associated with a high recurrence rate (80 to 92%) in subsequent pregnancies, a pattern that cannot be explained by genetic inheritance but is consistent with an alloimmune pathogenesis.

What are typical clinical features associated with this disease?

Extensive liver injury is typically present at birth, and some signs– such as placental edema, oligohydramnios, intrauterine growth retardation, prematurity, and stillbirth — can be detected antenatally. Hypoalbuminemia, hypoglycemia, coagulopathy, a low fibrinogen level, thrombocytopenia, and eventual multiorgan failure are the hallmarks of the disease. Low aminotransferase levels at birth are consistent with a long-standing antenatal process.

Morning Report Questions

Q: What diagnostic tests are obtained when clinical and laboratory findings suggest a diagnosis of neonatal hemochromatosis?

A: Gradient-echo MRI has become the standard noninvasive diagnostic procedure for neonatal hemochromatosis. All newborns have a relatively large amount of iron deposited in the liver because of prenatal maternal transfer; therefore, to make the diagnosis of neonatal hemochromatosis, abnormal iron storage in the pancreas, which is not seen in healthy newborns, must also be established.T1-weighted and T2-weighted MRI images can be helpful in detecting iron deposits in the liver, pancreas, and thyroid glands. The presence of iron deposits in the biopsy specimens of affected organs has become the standard in establishing the diagnosis. Since marked coagulopathy makes a liver biopsy exceedingly difficult to perform, biopsy of the minor salivary gland offers an excellent alternative.

Biopsy of the minor salivary gland is a useful method for detecting evidence of extrahepatic hemosiderosis and is a highly sensitive and specific test for neonatal hemochromatosis.

Figure 1. MRI Scans of the Liver.

Figure 2. Biopsy Specimens.

Q: What treatment options are available, and what survival rates are associated with this disease?

A: Therapy for neonatal hemochromatosis includes treatment for liver failure with antioxidant cocktails (including vitamin E, N-acetylcysteine, prostaglandins, and selenium), fresh-frozen plasma, and cryoprecipitate. Infusions of intravenous immune globulin (IVIG) and exchange transfusion have also been suggested. Exchange transfusion is performed to remove any maternal alloantibodies remaining in the fetal circulation, and IVIG is administered to displace specific reactive IgG antibodies that are bound to target antigens and to bind with circulating complement. Favorable outcomes among patients with neonatal hemochromatosis have been described; however, the prognosis remains seriously guarded, and the disease is associated with an overall survival of 36%. In a large case series, the survival rate was 51% among patients who had undergone a liver transplantation and 22% among those who had not undergone a transplantation.

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