Hemochromatosis Iron Overload

Hemochromatosis: Understanding Iron Overload and Its Impact on the Body

Hemochromatosis, commonly referred to as iron overload disorder, is a complex medical condition characterized by excessive absorption and accumulation of iron in the body’s tissues and organs. While iron is essential for numerous physiological functions, including oxygen transport and DNA synthesis, too much iron can become toxic, leading to serious organ damage over time. The disorder can be hereditary or acquired, with the hereditary form being most common in populations of Northern European descent.


The Basics of Iron Metabolism

Under normal conditions, the body regulates iron absorption based on its needs. The small intestine absorbs iron from food, and excess iron is stored in proteins such as ferritin and hemosiderin primarily in the liver, spleen, and bone marrow. Unlike other minerals, the body has no active mechanism for excreting excess iron; it relies on blood loss (e.g., menstruation, bleeding) to regulate total iron levels. When iron regulation fails—as it does in hemochromatosis—iron gradually accumulates to toxic levels.


Types of Hemochromatosis

  1. Hereditary Hemochromatosis (Primary)

    • Caused by genetic mutations, particularly in the HFE gene, with C282Y and H63D being the most common mutations.

    • The most frequent form is autosomal recessive, requiring two defective copies of the gene.

    • "Bronze Diabetes" is a term historically used to describe the triad of skin pigmentation, diabetes, and liver disease seen in hereditary hemochromatosis.

  2. Secondary Hemochromatosis

    • Acquired due to other conditions such as repeated blood transfusions (common in thalassemia or sickle cell anemia), chronic liver diseases, or iron-loading anemias.


Organ-Specific Effects of Iron Overload

Iron accumulation affects multiple organs, often causing progressive and irreversible damage:

1. Liver: The Primary Iron Reservoir

The liver is the first and most affected organ due to its central role in iron storage.

  • Cirrhosis: Scarring and fibrosis as hepatocytes become damaged.

  • Hepatocellular carcinoma: Increased cancer risk with longstanding liver damage.

  • Liver failure: Severe cases may lead to complete loss of liver function.

2. Heart: Cardiac Iron Deposition

Excess iron in the myocardium leads to:

  • Cardiomyopathy: The heart muscle becomes thickened or stiff, reducing its ability to pump blood efficiently.

  • Heart failure: Progressive weakening of heart function.

  • Arrhythmias: Irregular heartbeats due to electrical conduction disturbances caused by iron infiltration.

3. Pancreas: Disruption of Insulin Production

  • Iron deposits in pancreatic beta cells impair insulin secretion, causing diabetes mellitus.

  • When combined with hyperpigmentation, liver dysfunction, and diabetes, it manifests as bronze diabetes.

4. Joints and Musculoskeletal System

  • Iron can accumulate in joints leading to arthropathy, causing joint pain, stiffness, and arthritis-like symptoms.

  • Muscular weakness and fatigue are common but generally less severe compared to major organ damage.

5. Endocrine Glands

  • Hypogonadism, hypothyroidism, and other hormonal imbalances may develop due to iron deposition in the pituitary gland.


Ocular Manifestations of Hemochromatosis

Although rare, the eyes may exhibit signs of iron overload, especially in longstanding or severe cases:

Conjunctiva

  • Brown pigmentation along the limbus, particularly inferiorly and medially.

  • Pigment deposits may follow radial striations due to lymphatic channels.

  • Rarely, fusiform or berry aneurysms may appear in conjunctival vessels.

Cornea

Multiple patterns of corneal iron deposition have been described:

  • Hudson-Stรคhli lines
    Horizontal pigmented lines in the lower third of the cornea, typically in the elderly.

  • Stocker lines
    Vertical lines located near pterygia (growths on the eye’s conjunctiva).

  • Fleischer rings
    Circular iron deposits seen in keratoconus patients.

  • Ferry lines
    Golden-brown lines near filtering blebs in glaucoma surgery patients, correlating with bleb height.

Iron accumulates in the cornea through mechanisms like tear film pooling, stress-induced changes in epithelial cells, and increased receptor expression for iron-binding proteins like transferrin and lactoferrin.


Diagnosis of Hemochromatosis

Early diagnosis is critical to prevent irreversible organ damage. The diagnostic approach includes:

1. Blood Tests

  • Serum Ferritin: Elevated levels reflect increased iron stores.

  • Transferrin Saturation: High saturation suggests iron overload.

  • Total Iron Binding Capacity (TIBC): Often low or normal in hemochromatosis.

  • Serum Iron: Elevated.

2. Genetic Testing

  • Identification of HFE gene mutations (e.g., C282Y, H63D) confirms hereditary forms.

3. Liver Function Tests

  • Elevated liver enzymes may indicate liver damage.

4. Imaging

  • MRI with T2-weighted imaging can non-invasively measure hepatic iron concentration.

5. Liver Biopsy (Rarely Required Today)

  • Used in uncertain cases or to assess liver fibrosis or cirrhosis.


Management and Treatment

While hereditary hemochromatosis cannot be prevented, its complications can often be minimized or avoided through early intervention:

Phlebotomy (Therapeutic Blood Removal)

  • The cornerstone of treatment.

  • Regular removal of blood (typically 500 mL weekly or biweekly) reduces total body iron.

Chelation Therapy

  • Used when phlebotomy is not possible (e.g., anemia or poor venous access).

  • Iron chelators bind iron for excretion.

Dietary Management

  • Avoid iron supplements and high-iron foods (e.g., organ meats, fortified cereals).

  • Limit vitamin C intake as it increases iron absorption.

  • Avoid alcohol to reduce liver strain.

Monitoring

  • Regular monitoring of ferritin, transferrin saturation, and organ function.


Nutritional Interactions: Iron, Zinc, and Other Metals

Iron metabolism interacts with the absorption and metabolism of other minerals:

  • Zinc Absorption:
    Iron supplements can impair zinc absorption if taken together. However, when both are ingested through a balanced diet, their absorption is generally unaffected.

  • Cadmium Exposure:
    Environmental cadmium also inhibits zinc absorption, compounding nutritional challenges.

Proper management of iron levels should also include attention to maintaining adequate zinc and copper status, especially during long-term treatment.


Prognosis

When diagnosed early and treated adequately, many individuals with hemochromatosis live normal, healthy lives. However, untreated iron overload can lead to severe, life-threatening complications including liver failure, heart disease, diabetes, and increased cancer risk.

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Additional Information:

What blocks zinc absorption?
Iron can have a negative effect on zinc absorption, if given together in a supplement, whereas no effect is observed when the same amounts are present in a meal as fortificants. Cadmium, which is increasing in the environment, also inhibits zinc absorption.

Reference:

Dietary factors influencing zinc absorption:
https://pubmed.ncbi.nlm.nih.gov/10801947/

Ocular Manifestations of Hemochromatosis and Iron-Overloaded States
https://eyewiki.org/Ocular_Manifestations_of_Hemochromatosis_and_Iron-Overloaded_States#:~:text=Excess%20iron%20has%20potential%20to,to%20age%2Drelated%20macular%20degeneration.

Iron Overload
https://www.ncbi.nlm.nih.gov/books/NBK526131/

Iron overload HYPERFERRITINEMIA
https://swaresearch.blogspot.com/2024/01/iron-overload-hyperferritinemia.html

Effect of natron administration on the antioxidant status and lipid profile of rats
https://ift.onlinelibrary.wiley.com/doi/abs/10.1111/1750-3841.15480

 

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9



 

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