Haemochromatosis is a genetic disorder causing the body to absorb and store an excessive amount of iron from the diet, a condition commonly referred to as iron overload. Normally, the body regulates iron absorption with precision, but this mechanism fails, leading to a slow, toxic accumulation of the mineral. This excess iron is deposited in various organs and tissues, where it interferes with normal cellular function and causes progressive damage. Untreated iron overload can eventually lead to severe, life-threatening complications, such as organ failure, making early detection important for successful long-term management.
Understanding the Mechanisms of Iron Overload
The most common cause of iron overload is Hereditary Haemochromatosis (HH), resulting from a fault in the \(HFE\) gene. This gene provides instructions for a protein that helps regulate iron absorption from the gut. The primary regulator of systemic iron balance is hepcidin, a hormone that limits the amount of iron released into the bloodstream.
In most HH cases, the \(HFE\) gene contains the C282Y mutation. When inherited from both parents, this mutation severely impairs the gene’s function, disrupting hepcidin production. This genetic fault signals to the body that iron stores are low, even when they are high. Consequently, the digestive system absorbs far more iron than necessary, leading to gradual buildup in major organs.
Inheriting two copies of the faulty gene does not guarantee the development of severe iron overload, as the condition shows variable penetrance. However, the continued absorption causes iron to accumulate systemically, primarily in the liver, pancreas, heart, and joints. While hereditary forms are the most common, secondary iron overload can occur due to conditions like chronic anemias requiring frequent blood transfusions.
Recognizing the Physical Manifestations
The symptoms of iron overload are often nonspecific and subtle in the early stages, making Haemochromatosis difficult to diagnose based on physical signs alone. Many individuals initially report vague complaints that overlap with other common conditions, such as persistent weakness and fatigue. Joint pain, known as arthralgia, is also an early and common complaint, frequently affecting the knuckles of the second and third fingers.
As iron accumulation progresses, the excess metal causes organ-specific damage, leading to more distinct symptoms. The liver is often the first organ affected, resulting in enlargement (hepatomegaly), abdominal pain, and eventually advanced scarring, or cirrhosis. Untreated cirrhosis significantly raises the risk of developing liver cancer.
Iron deposition in the pancreas can damage insulin-producing cells, leading to diabetes mellitus. When iron accumulates in the heart muscle, it impairs the organ’s ability to pump blood effectively, potentially causing congestive heart failure or irregular heart rhythms (arrhythmias). Furthermore, a distinctive darkening of the skin, sometimes described as a bronze or slate-gray color, occurs due to iron deposits in skin cells.
The endocrine system is also vulnerable to iron toxicity, where deposits in the pituitary gland or gonads can result in reproductive problems. Men may experience loss of sex drive and erectile dysfunction, while women may see menstrual cycle abnormalities or early menopause. Early diagnosis before significant organ damage occurs is important because certain symptoms, such as joint damage, may not fully reverse even after iron levels are normalized.
Steps to Confirm a Diagnosis
The diagnostic process typically begins with initial blood tests to assess the body’s iron status. The first measure is the serum transferrin saturation (TSAT), which indicates the percentage of the iron-transport protein, transferrin, currently bound to iron. A consistently elevated TSAT, often above 45%, strongly indicates iron hyperabsorption and warrants further investigation.
The second key blood test is the serum ferritin level, which reflects the amount of iron stored in the body’s tissues. Elevated ferritin levels, typically above 200 micrograms per liter in premenopausal women and 300 micrograms per liter in men and postmenopausal women, suggest iron overload. However, ferritin is also an acute-phase reactant, meaning its level can be temporarily raised by inflammation or infection, requiring interpretation alongside the TSAT and clinical context.
If these initial iron studies are consistently abnormal, the next step is genetic testing for specific \(HFE\) gene mutations. This test confirms Hereditary Haemochromatosis by identifying two copies of the C282Y mutation, or a combination of C282Y and the less common H63D mutation. Genetic testing is definitive for the hereditary form and is often performed before symptoms of organ damage appear, especially when screening family members.
In cases where non-HFE related haemochromatosis is suspected, or when the extent of iron damage is a concern, additional tests are used. Noninvasive methods like Magnetic Resonance Imaging (MRI) can accurately measure the concentration of iron deposited in the liver and heart. A liver biopsy, while less common due to improved imaging, can still be performed to directly assess iron concentration and determine the degree of existing liver fibrosis or cirrhosis.
Treatment and Long-Term Management
The primary and most effective treatment for Hereditary Haemochromatosis is therapeutic phlebotomy, which involves regularly removing blood to reduce the overall iron load. This procedure is similar to a standard blood donation, where approximately 500 milliliters of blood is removed from a vein. Removing iron-rich red blood cells forces the body to use stored iron to produce new ones, thereby lowering the toxic accumulation.
Treatment is divided into two phases: induction and maintenance. During the induction phase, blood is removed frequently, often weekly, until the serum ferritin level drops to a target range, typically between 50 and 100 micrograms per liter. Once iron stores are depleted, the maintenance phase requires less frequent blood removal, usually two to four times per year, to keep iron levels healthy for life.
For patients who cannot tolerate phlebotomy due to poor vein access, anemia, or certain heart conditions, chelation therapy provides an alternative. This treatment involves taking medications that bind to excess iron, allowing it to be excreted through urine or stool. Lifestyle adjustments are also important, including avoiding iron supplements and multivitamins containing iron. Limiting alcohol intake is advised, as it can accelerate liver damage and increase iron absorption.