What Is Neonatal Hemochromatosis?
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Neonatal Hemochromatosis: Causes, Symptoms, Diagnosis, and Treatment

Published on Jan 05, 2023 and last reviewed on Aug 18, 2023   -  5 min read


Neonatal hemochromatosis is the abnormal accumulation of iron within the body of newborn babies. Read this article to have an understanding of this condition.

What Is Neonatal Hemochromatosis?

The liver is the primary site for the storage of iron. Neonatal hemochromatosis is a severe liver disorder of a fetal or perinatal onset and is characterized by the deposition of iron in extrahepatic sites. Hepatic iron disease (HFE) is the most common hemochromatosis disorder in the European and American populations; neonatal hemochromatosis parrots HFE with the iron deposition and accumulation criteria. However, both lack any concrete association.

Who Is Susceptible to Neonatal Hemochromatosis?

First reported in 1957, neonatal hemochromatosis is a rare disorder with no incidence studies. However, a prevalence of 0.03 to 0.038 or a heterozygosity prevalence of six to seven percent is reported. The condition has been documented in Filipinos, African Americans, Hong Kong Chinese, and white infant populations. There is no evidence of any racial predilection or gender predominance. Some studies have shown the onset secondary to liver damage between 16 to 20 weeks of gestation. A mother bearing an affected child is reported to have an 80 percent chance of bearing another child with the same condition.

What Is the Cause of Neonatal Hemochromatosis?

The exact cause of neonatal hemochromatosis still alludes to discovery. However, some evidence suggests that it is caused due to maternal-fetal alloimmunity (gestational alloimmune liver disease). Owing to repeated occurrences in offspring and lack of any inheritance evidence, neonatal hemochromatosis is concluded to be congenital and familial but not inherited.

Most studies report that a high number of cases occur secondary to fetal liver damage due to gestational alloimmune liver disease. A fetus is guarded by an army of maternal antibodies recruited via the placenta. However, in alloimmune disorders, maternal antibodies misrecognize some of the fetal tissues and cause havoc over them. In this case, the antibodies corrode the hepatic (liver) cells. Damage to the hepatocytes (cells of the liver) makes the organ unable to store iron, which is then deposited within the connective tissues. Literary evidence of women bearing multiple children with neonatal hemochromatosis, even with different fathers, may suggest material fetal alloimmunity as the underlying cause. Placental transmission of infection that causes liver damage is also believed to be causative of the condition.

However, non-alloimmunity-associated neonatal hemochromatosis cases have also been reported in association with genetic abnormalities like DGUOK gene mutations, bile acid synthetic defects, and trisomy 21.

What Is the Pathophysiology of Neonatal Hemochromatosis?

Depletion of hepatocytes in the fetus extends to the hepatic lobule and depletion of pancreatic parenchyma as well. It is also possible to cause a myocardial and endocrine system failure. These changes may be seen antenatally and may cause placental edema and oligohydramnios (decreased amniotic volume). The infant may be stillborn, delivered premature, or have intrauterine growth restriction (IUGR).

Some of the pathophysiological effects of neonatal hemochromatosis have been marked in postmortem analysis. These include

What Are the Signs and Symptoms of Neonatal Hemochromatosis?

Some of the clinical features of neonatal hemochromatosis are:

  • Placental edema.

  • Intrauterine growth restriction (IUGR).

  • Edema without ascites (accumulation of fluid in the abdomen).

  • Disseminated intravascular coagulation or DIC (a condition in which blood clots form throughout the body).

  • Jaundice.

  • Splenomegaly (enlargement of the spleen).

  • Hypoglycemia (low blood sugar).

  • Coagulopathy (blood clotting abnormalities).

  • Oliguria (decrease or absence of urine).

  • Cirrhosis (liver scarring).

How to Diagnose Neonatal Hemochromatosis?

Neonatal hemochromatosis may be suspected in babies illustrating antenatal or neonatal liver damage. Some of the tests that the pediatrician may order are:

  • CBC (complete blood count) and differential count: to evaluate anemic or thrombocytopenic conditions.

  • Total and direct bilirubin levels may be increased.

  • Hemolysis shows decreased reticulocyte count.

  • Glucose level.

  • Albumin levels may be low due to the sustaining edema.

  • Urine analysis may show oliguria and any renal involvement.

  • BUN (blood urea nitrogen) and creatinine levels can be done to evaluate renal functions.

  • Prothrombin time, activated partial thromboplastin time, and fibrin split products to rule out hemorrhagic etiology.

  • Low but hypo-saturated transferrin levels.

  • Low total iron binding capacity.

  • Highly elevated cytoferrin levels.

  • LDH (lactic acid dehydrogenase) levels seem elevated.

  • Mildly elevated aminotransferase levels.

  • Iron levels are usually normal.

MRI (magnetic resonance imaging) and ultrasonography are the most helpful modes of diagnosing neonatal hemochromatosis. Ultrasonography may show patency of the ductus venosus (a shunt that allows oxygenated blood in the umbilical vein to bypass the liver and is essential for normal fetal circulation), which is due to fetal liver damage and the following portocaval shunting. The magnetic field of MRI can detect increased levels of iron deposits and can also detect areas of pancreatic and spleen siderosis (iron deposition). Inutero MRI studies do not demonstrate any siderosis or existing neonatal hemochromatosis.

Although quite difficult to perform owing to the increased tendency to bleed, a biopsy is a very useful diagnostic modality. A punch biopsy of the oral mucosa is a potential alternative. Minor salivary glands of the lower lip mucosa can be the donor site for biopsy samples owing to the possible siderosis in the salivary gland and also due to the ease of access for bleeding control.

How to Treat Neonatal Hemochromatosis?

Mothers with a history of neonatal hemochromatosis-affected infants are treated with immunoglobulin therapy from 18 weeks of gestation. Despite the lack of an absolute cure, infants have been treated with various combinations of antioxidants, cryoprotective agents, and chelation. The primary focus should be on the ABC (airway, breathing, and circulation) of the infant and their respective management to ensure the stability of all three vitals. General supportive therapy may include fresh-frozen plasma (FFP), platelets, cryoprecipitate, and packed red blood cells (PRBCs). Pharmacotherapeutic options include antioxidant cocktails of N -acetylcysteine, alpha-tocopherol polyethylene glycol succinate (TPGS), and selenium in various concentrations and amounts. Chelating agent-Deferoxamine, prostaglandins- Alprostadil (for their cytoprotective nature), surfactants-Beractant, Calfactant, and Poractant alfa, and inotropic agents-Dopamine, and Dobutamine have been administered to the affected infants.

What Is the Differential Diagnosis of Neonatal Hemochromatosis?

  • Galactose-1-phosphate uridyltransferases deficiency (galactosemia).

  • Parvovirus B19 infection.

  • Pediatric cytomegalovirus infection.

  • Pediatric echovirus.

  • Pediatric hepatitis A, B, or C.

  • Pediatric rubella.

  • Pediatric syphilis.

  • Pediatric toxoplasmosis

  • Tyrosinemia.

What Are the Complications of Neonatal Hemochromatosis?

  • Congenital cirrhosis.

  • Acute liver failure.

  • Fetal demise.

  • Stillbirth.

  • Hydrops.

  • Growth restriction.


Neonatal hemochromatosis, although rare, is a serious condition that may even cause the intrauterine demise of the fetus. Mothers with a suspected history of gestational alloimmune liver disease should be put under IVIG (intravenous immunoglobulin) therapy which can improve the chances of the fetus. Such high-risk pregnancies require a maternal-fetal medicine specialist for an uneventful pregnancy.

Last reviewed at:
18 Aug 2023  -  5 min read




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