Iron Overload

Iron overload, also known as haemochromatosis or hemochromatosis, is a condition characterised by the abnormal accumulation of iron in the body, leading to organ damage primarily through oxidative stress. This condition can be hereditary or secondary to repeated blood transfusions. Iron deposition frequently occurs in the liver, pancreas, heart, skin, and joints. Early detection often limits symptoms to chronic malaise, arthralgia, and hepatomegaly.

Signs and Symptoms

Organs most commonly affected by hemochromatosis include the liver, heart, and endocrine glands. Clinical presentations vary, affecting multiple organ systems:

• Liver: Chronic liver disease and cirrhosis.
• Heart: Heart failure and arrhythmias.
• Endocrine: Diabetes due to iron deposition in pancreatic beta cells, and hypogonadism leading to low sex drive and infertility.
• Metabolism: Selective iron deposition in islet beta cells causes diabetes.
• Skeletal: Arthritis from iron deposition in joints, commonly affecting hands, wrists, elbows, hips, knees, and ankles.
• Skin: Darkening or bronzing, known as melanoderma.

"Bronze diabetes" describes the combination of secondary diabetes and skin darkening.

Causes

Hemochromatosis can be:

Primary Hemochromatosis

Hereditary hemochromatosis is an autosomal recessive disorder, prevalent in European ancestry, particularly involving mutations of the HFE gene on chromosome 6. This leads to increased intestinal iron absorption and progressive tissue iron deposition, often presenting in midlife with a range of symptoms including hepatic cirrhosis, cardiomyopathy, diabetes, arthritis, and hyperpigmentation.

Secondary Hemochromatosis

Causes include chronic hemolysis, multiple blood transfusions, excessive iron supplements, and certain liver disorders combined with predisposing factors.

Pathophysiology

Defects in iron metabolism, particularly involving hepcidin, play a very important role. Hepcidin inhibits iron absorption and mobilisation. In hereditary hemochromatosis, mutations lead to decreased hepcidin production, resulting in unregulated iron absorption and mobilisation. This causes iron deposition, especially in the liver and joints, leading to oxidative stress and damage.

Diagnosis

Blood Test

Serum ferritin levels, transferrin saturation, and total iron binding capacity are initial tests. Elevated ferritin levels suggest iron overload but must be interpreted cautiously due to other potential causes of elevation.

Genetics

HFE gene mutation testing confirms hereditary hemochromatosis. A positive test for these mutations, in conjunction with iron overload, establishes the diagnosis.

Biopsy

Liver biopsy and analysis of hepatic iron index confirm hemochromatosis in ambiguous cases.

Imaging

MRI estimates iron deposition levels in the liver and heart, aiding in treatment and prognosis.

Treatment

Phlebotomy

Phlebotomy is the mainstay treatment, involving regular blood draws to reduce iron levels. Initially, frequent sessions normalise iron levels, followed by maintenance phlebotomies. Phlebotomy can reverse liver fibrosis and alleviate some symptoms but is less effective for chronic arthritis.

Diet

Dietary restrictions on iron are generally unnecessary during phlebotomy treatment, although reducing dietary iron can lessen the need for blood draws. Vitamin C and iron supplements should be avoided. Alcohol should also be avoided due to compounded liver damage risk.

Medication

For those intolerant to phlebotomy, iron-chelating agents like deferoxamine, deferasirox, and deferiprone are used to enhance iron elimination.

Chelating Polymers

Polymeric chelators, which limit iron uptake in the gastrointestinal tract, provide a minimally invasive treatment option with fewer side effects.

Prognosis

If treated before liver damage, patients can expect a normal life expectancy. The risk of liver damage and hepatocellular carcinoma increases with higher ferritin levels, alcohol use, diabetes, and advanced liver iron levels. Men have a higher risk of death and liver fibrosis compared to women, likely due to protective effects of menstruation and pregnancy in females.

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Self-assessment MCQs (single best answer)

What is another name for iron overload?

Which gene is commonly mutated in hereditary hemochromatosis?

What is the primary treatment for iron overload?

Which organ is most commonly affected by iron deposition in hemochromatosis?

What is the role of hepcidin in iron metabolism?

What symptom is described by the term "bronze diabetes"?

Which test is used to confirm hereditary hemochromatosis?

What is the significance of elevated serum ferritin levels?

Which of the following is a secondary cause of hemochromatosis?

What is a potential complication of untreated iron overload?