| Neonatal hemochromatosis |
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Neonatal Hemochromatosis is a rare, severe, and non-hereditary disease. It is a secondary iron overload with extrahepatic siderosis caused by severe fetal liver injury. This disease is not a type of hereditary hemochromatosis.
Almost all cases of neonatal hemochromatosis (NH) are caused by Gestational Alloimmune Liver Disease (GALD). In GALD, the mother becomes sensitized to a fetal hepatic antigen; the resulting IgG antibodies cross the placenta, activate complement, and destroy fetal hepatocytes, triggering the iron-overload phenotype that defines NH. The NH could be classified as a congenital alloimmune hepatitis. [1] Its estimated prevalence in the world is <1 case per 1,000,000 live births. The risk of GALD-NH occurring in subsequent pregnancies is very high (80-95%), but prophylactic high-dose maternal intravenous immunoglobulin (IVIG) therapy reduces the recurrence rate to 5-10%. GALD has other forms of presentation besides NH.
Although GALD-associated NH (GALD-NH) predominates, the “NH syndrome” pattern can also arise from other forms of fetal or perinatal liver injury (infections, metabolic disorders, bile acid synthesis defects, etc).
The diagnosis of NH is based on a stepwise approach combining clinical findings, laboratory tests, imaging studies and targeted biopsies.
The differential diagnosis of NH should include all causes of acute liver failure and secondary siderosis in the newborn as congenital infections, inborn errors of metabolism, hematologic and vascular disorders, cholestasis and biliary anomalies, hemorrhage, portal vein thrombosis, and perfusion disorders.[ citation needed ]
In 2004, effective treatment of the disease was limited to liver transplants. [2]
Any neonate with suspected GALD-NH should receive an initial dose of intravenous immunoglobulin G (IVIG) while diagnostic work-up is in progress. First-line definitive therapy combines a double-volume exchange transfusion (DVET) to clear maternal antibodies with high-dose IVIG to block complement-mediated hepatocyte injury. Improvement in coagulation (INR) may take 4-6 weeks as the liver regenerates.
Despite DVET + IVIG, approximately 20% of infants still require liver transplantation when medical therapy fails or liver damage is irreversible.
High-dose maternal IVIG weekly starting at 14-18 week’s gestation and continue through delivery reduces recurrence of GALD-NH in subsequent pregnancies.