eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Hemochromatosis, Neonatal: Differential Diagnoses & Workup

Author: Roland L Boyd, DO, FAAP, FACOP, Neonatologist, Section of Neonatology, Neonatal Services Limited
Coauthor(s): Jatinder Bhatia, MBBS, Professor of Pediatrics, Chief, Section of Neonatology, Department of Pediatrics, Medical College of Georgia; Joseph H Clark, MD, Professor, Department of Pediatric, Division of Gastroenterology, Medical College of Georgia
Contributor Information and Disclosures

Updated: Mar 6, 2008

Differential Diagnoses

Galactose-1-Phosphate Uridyltransferase Deficiency (Galactosemia)

Other Problems to Be Considered

Adenovirus
Coxsackie virus
Echovirus
Herpes virus
Alpha1-antitrypsin (A1At) deficiency
Maternofetal blood group incompatibility
Hemophagocytic syndrome
Hepatic infarct
Maternal systemic lupus erythematosus
Mitochondrial disease with hepatic predominance
Not hepatitis viruses
Ischemia/abnormal perfusion
Maternal shock
Placentitis
Fetal heart disease
Myelodysplasia
Congenital leukemia
Hemangiomatosis

Workup

Laboratory Studies

  • When liver failure is diagnosed in the first 1-2 days of life, neonatal hemochromatosis is by far the most common diagnosis. Afterward, many other conditions can manifest and must be excluded. They include all other causes of hepatic failure, including infective, metabolic, and hemorrhagic causes. The following are other causes of liver failure in the newborn:
  • Relevant laboratory tests and findings include the following:
    • CBC count with differential - To check for anemia and thrombocytopenia
    • Total and direct bilirubin levels - Elevated
    • Reticulocyte count - To check for any signs of hemolysis
    • Glucose level - Because infants with neonatal hemochromatosis can present with hypoglycemia
    • Albumin level - Because it may be low, which accounts for the infants' edema
    • Urinalysis - To check for causes of oliguria and any renal involvement
    • BUN and creatinine levels - To evaluate renal function
    • Prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrin split products - To rule out any hemorrhagic causes
    • Transferrin level (one of the most common findings) - Low but hypersaturated
    • Serum ferritin levels - Elevated
    • Total iron-binding capacity - Low
    • Cytoferrin level - Markedly elevated
    • Lactic acid dehydrogenase (LDH) level - Markedly elevated
    • Aminotransferases level - Mildly elevated
    • Iron levels - Usually in the reference range

Imaging Studies

  • MRI is the most helpful study in the diagnosis of neonatal hemochromatosis.4
    • MRI can be used to detect increased levels of iron in the liver compared with levels in normal tissues.
    • MRI can be used to document any areas of siderosis of the pancreas and myocardium. Absence of siderosis of the spleen may also be observed.
    • MRI of infants in utero has not demonstrated any siderosis or signs of neonatal hemochromatosis.
  • Ultrasonography demonstrates patency of the ductus venosum; this is because of liver injury and, thus, portocaval shunting occurs.

Procedures

  • Biopsy
    • Liver biopsy is not easily performed in these infants because of the increased tendency of bleeding, but it is helpful in aiding in the diagnosis.
    • Another option is to perform a punch biopsy of the oral mucosa. This area is used secondary to the small salivary glands. Punch biopsy is performed by using 3-mm punch biopsy of the mucosa of the lower lip, and bleeding can be controlled. Salivary glands are siderotic if neonatal hemochromatosis is present.

Histologic Findings

Microscopic examination of the liver reveals that the hepatocytes have giant-cell transformation or pseudoacinar transformation with bile plugs, or no hepatocytes are present at all. Also, the hepatocytes may show siderosis, while Kupffer cells are spared. Scarring may be present from macrophages, which contain high levels of stainable iron. Bile duct is proliferated. The spleen, lymph nodes, and bone marrow contain a small amount of stainable iron. The placenta is not siderotic, and villitis has not been reported.

More on Hemochromatosis, Neonatal

Overview: Hemochromatosis, Neonatal
Differential Diagnoses & Workup: Hemochromatosis, Neonatal
Treatment & Medication: Hemochromatosis, Neonatal
Follow-up: Hemochromatosis, Neonatal
References
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References

  1. Adams PC, Searle J. Neonatal hemochromatosis: a case and review of the literature. Am J Gastroenterol. Apr 1988;83(4):422-5. [Medline].

  2. Muller-Berghaus J, Knisely AS, Zaum R, et al. Neonatal haemochromatosis: report of a patient with favourable outcome. Eur J Pediatr. Apr 1997;156(4):296-8. [Medline].

  3. Colletti RB, Clemmons JJ. Familial neonatal hemochromatosis with survival. J Pediatr Gastroenterol Nutr. Jan-Feb 1988;7(1):39-45. [Medline].

  4. Liet JM, Urtin-Hostein C, Joubert M, et al. Neonatal hemochromatosis [in French]. Arch Pediatr. Jan 2000;7(1):40-4. [Medline].

  5. Sigurdsson L, Reyes J, Kocoshis SA, et al. Neonatal hemochromatosis: outcomes of pharmacologic and surgical therapies. J Pediatr Gastroenterol Nutr. Jan 1998;26(1):85-9. [Medline].

  6. Whitington PF, Hibbard JU. High-dose immunoglobulin during pregnancy for recurrent neonatal haemochromatosis. Lancet. Nov 6-12 2004;364(9446):1690-8. [Medline].

  7. Whitington PF, Kelly S, Ekong UD. Neonatal hemochromatosis: fetal liver disease leading to liver failure in the fetus and newborn. Pediatr Transplant. Oct 2005;9(5):640-5. [Medline].

  8. Neonatal gastroenterology. In: Neu J, ed. Clinical Perinatology. Vol 23. Philadelphia, PA: WB Saunders; 1996:327-8.

  9. Gracey M, Burke V. Metabolic disorders. In: Pediatric Gastroenterology and Hepatology. 3rd ed. Boston, MA: Blackwell Scientific; 1991:611.

  10. Knisely AS. Neonatal hemochromatosis. Adv Pediatr. 1992;39:383-403. [Medline].

  11. Lebenthal E. Inherited metabolic liver disorders. In: Textbook of Gastroenterology and Nutrition in Infancy. 2nd ed. New York, NY: Raven; 1990:981-2.

  12. Rand EB, McClenathan DT, Whitington PF. Neonatal hemochromatosis: report of successful orthotopic liver transplantation. J Pediatr Gastroenterol Nutr. Oct 1992;15(3):325-9. [Medline].

  13. Rodrigues FM, Kallas M, Nash R. Neonatal hemochromatosis in eleven families: pattern of presentation and outcome [abstr]. Hepatol. 1999;9:1882-5.

  14. United States Pharmacopeial Convention Inc. Drug Information for the Health Care Professional. Vol 1. 1997:18-21, 51-3, 1145-8, 2589-90.

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Further Reading

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Keywords

neonatal hemochromatosis, NH, neonatal iron storage disease, neonatal iron storage disorder, perinatal hemochromatosis fulminant, hepatic failure in utero, hepatic iron disease, HFE disease, siderosis, liver disease, placental edema, oligohydramnios, intrauterine growth retardation, IUGR, polyhydramnios, hyperpigmented skin, hepatomegaly, diabetes mellitus, oligoria, splenomegaly

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Contributor Information and Disclosures

Author

Roland L Boyd, DO, FAAP, FACOP, Neonatologist, Section of Neonatology, Neonatal Services Limited
Roland L Boyd, DO, FAAP, FACOP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, and American College of Osteopathic Pediatricians
Disclosure: Nothing to disclose.

Coauthor(s)

Jatinder Bhatia, MBBS, Professor of Pediatrics, Chief, Section of Neonatology, Department of Pediatrics, Medical College of Georgia
Jatinder Bhatia, MBBS is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Dietetic Association, American Federation for Clinical Research, American Pediatric Society, American Society for Clinical Nutrition, American Society for Parenteral and Enteral Nutrition, New York Academy of Sciences, Society for Pediatric Research, and Southern Society for Pediatric Research
Disclosure: Mead Johnson Consulting fee Consulting; Mead Johnson Honoraria Speaking and teaching; Dey LP Consulting fee Consulting; Dey LP Honoraria Speaking and teaching; Wyeth Grant/research funds Other; Med Immune Grant/research funds Other; Ovation  None

Joseph H Clark, MD, Professor, Department of Pediatric, Division of Gastroenterology, Medical College of Georgia
Joseph H Clark, MD is a member of the following medical societies: American Academy of Pediatrics, American Gastroenterological Association, American Society for Parenteral and Enteral Nutrition, North American Society for Pediatric Gastroenterology and Nutrition, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Hisham Nazer, MBBCh, FRCP, Professor of Pediatrics, Consultant in Pediatric Gastroenterology, Hepatology and Clinical Nutrition, Bushnaq Medical Centre, University of Jordan
Hisham Nazer, MBBCh, FRCP is a member of the following medical societies: Royal College of Paediatrics and Child Health and Royal College of Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

David Piccoli, MD, Chief, Division of Gastroenterology and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine
David Piccoli, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

CME Editor

Steven M Schwarz, MD, FAAP, FACN, AGAF, Professor of Pediatrics, State University of New York, Downstate Medical Center College of Medicine; Distinguished Lecturer, New York Medical College, School of Public Health
Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research
Disclosure: TAP Pharmaceuticals Honoraria Speaking and teaching; Curemark, LLC Consulting fee Board membership

Chief Editor

Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine
Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

 
 
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