1Professor Pathology, Medical University of the Americas, Saint Kitts and Nevis
2DNB Radiation Oncology, Assistant Professor, Clinical Skills, Medical University of the Americas, Saint Kitts and Nevis
3MD Pharmacology, Assistant Professor, Clinical Skills, Medical University of the Americas, Saint Kitts and Nevis
4Senior Associate Lecturer in Pediatrics, Faculty of Medical Sciences, The University of the West Indies, Barbados
Hereditary hemochromatosis (also called bronze diabetes) is a common autosomal recessive disorder in the Caucasian population characterized by high levels of iron accumulation due to increased dietary absorption despite a normal intake. Most cases are seen in homozygotes with a mutation of the hemochromatosis gene (HFE) protein, the common mutation being C282Y. The excess iron is deposited in many tissues as hemosiderin leading to multiple organ damage.
Most cases of hereditary hemochromatosis are asymptomatic or manifest with nonspecific symptoms in adulthood, usually between 30 to 50 years of age. They are often discovered incidentally when abnormal iron indices are noted as part of routine chemistry screening for other conditions or during screening when a family member or relative is diagnosed with hemochromatosis.
Initial testing should include testing for serum ferritin and the serum transferrin saturation, which are usually increased. Further testing is considered if the ferritin levels exceed 200 µg/L (females) or 300 µg/L (males or postmenopausal females) or if the transferrin saturation (TSAT) is greater than 45%.
Total iron-binding capacity (TIBC) values > 450 mcg/dL or > 80.55 mmol/L can be helpful in diagnosing pathological iron accumulation. The negative predictive value is 97% for iron overload with normal serum ferritin and TSAT < 45%. Hyperferritinemia alone can be a rather non-specific finding, and most people with high ferritin levels need not suffer from hemochromatosis since it is often elevated in the setting of inflammation or malignancy. A persistently increased TSAT level > 45% is a more reliable indicator of hemochromatosis. Other findings that would elicit suspicion of hemochromatosis include imaging evidence of iron overload in the liver on MRI or iron deposits in hepatocytes on a liver biopsy.
Absence of acquired risk factors for hepcidin deficiency like alcohol abuse or end-stage liver disease favor the possibility of hereditary hemochromatosis. Secondary causes of iron overload must be excluded.
Since there is no cure, it is important to detect this condition early when the patient has not developed features related to cirrhosis or irreversible tissue damage. This article outlines the approach to patients with hereditary hemochromatosis and reviews the role of various laboratory tests and investigations in evaluating such cases.
Keywords: Hereditary Hemochromatosis; Total Iron-Binding Capacity (TIBC); Transferrin Saturation (TSAT); Hemochromatosis Gene (HFE)
Jeevan Divakaran., et al. Recent Update in Diagnostic Evaluation of Hereditary Hemochromatosis. EC Paediatrics 12.7 (2023): 72-81.
© 2023 Jeevan Divakaran., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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