Iron Overload

What is Iron Overload?

Iron is a very important substance that our bodies need for various crucial functions like carrying oxygen, creating energy, and assisting our immune system. However, sometimes, too much iron can build up in the body, a condition known as iron overload. The most common cause of iron overload is a genetic mutation that leads to a disease called hemochromatosis. However, excess iron can also accumulate in the body due to other causes. These include receiving blood transfusions, breaking down of red blood cells, and consuming too much iron in our diets.

When there’s too much iron in the body, it gets stored in organs across the body and can cause damage by creating harmful substances called reactive oxygen species. The organs that are mainly affected are the liver, heart, and endocrine glands (glands that produce hormones). The symptoms and related diseases that result from this depend on which organ is damaged. It’s very important to understand this condition and manage it effectively in medical practice in order to avoid potential organ damage.

What Causes Iron Overload?

Primary iron overload, a condition where there’s too much iron in the body, is usually inherited. Hereditary hemochromatosis is the main example of this. Back in 1996, scientists found two specific changes in a specific gene called the HFE gene, known as C282Y and H63D, which were linked to this type of iron overload. The most common is C282Y, which has a hand in the regulation of a hormone called hepcidin. There are other, less common genetic mutations tied to primary iron overload found in other genes, like HAMP, HJV, TFR2, and SLC40A1. These types of mutations are called non-HFE hemochromatosis.

Hemochromatosis used to be classified into four types. Type 1 is the classic type resulting from an HFE gene mutation (C282Y or H63D). The other types were known as non-classical. Type 2A is caused by a HAMP mutation, Type 2B a HJV mutation, Type 3 a TFR2 mutation, and Type 4, an SLC40A1 mutation. A newer system has been proposed which classifies hemochromatosis as either HFE-related or non-HFE-related, and digenic. Type 1 is now part of the HFE-related group, and includes having one copy of the C282Y mutation along with other rare variants of the HFE gene. Types 2, 3, and 4 are part of the non-HFE-related group. ‘Digenic’ refers to having two different types of gene mutations, which can be either HFE or non-HFE-related.

You can also get iron overload not through inheritance but simply by having too much iron introduced into the body. This can happen through blood transfusions, having too much iron in your diet, or processes within the body that destroy red blood cells.

Risk Factors and Frequency for Iron Overload

It’s estimated that around 16 million Americans have iron overload, either due to inherited conditions or other causes. Hereditary hemochromatosis, an example of an iron overload condition, is more commonly found among white people of European backgrounds. A study found that in Europe, 0.4% of people had two copies of the C282Y mutation (homozygous) and 9.2% had one copy (heterozygous). In North America, the numbers were similar, with 0.5% homozygous and 9% heterozygous. It’s estimated that 1 out of every 200 white patients in the US has iron overload, and between 10% and 14% are carriers of the genetic mutation.

The HEIRS study, which looked at the prevalence of the C282Y mutation in the US and Canada, found that non-Hispanic whites (0.44%), Native and Indigenous Americans (0.11%), and Hispanics (0.027%) had the mutation. By contrast, a study in Ireland found a higher rate, with 1.2% of individuals identified as homozygous for the C282Y mutation.

Signs and Symptoms of Iron Overload

Hemochromatosis is a condition where the body absorbs too much iron. This condition may not show any signs or symptoms until adulthood, typically in individuals over 30. However, in non-HFE-related hemochromatosis, symptoms can start appearing when individuals are between 20 to 30 years old.

Three out of four people may not show any symptoms even when they have an overload of iron in their body. When symptoms do occur, they are typically related to the impact on specific organs. Symptoms can include feeling tired all the time, joint pain, belly pain, enlarged liver, irregular heartbeat, lowered sex drive, high blood sugar levels, darker skin color, and feelings of sadness or depression. It’s worth noting that men are more likely to show symptoms than women, particularly because women lose some iron every month during their period.

Feeling constantly tired
Joint pain
Belly pain
Enlarged liver
Irregular heartbeat
Lower sex drive
High blood sugar levels
Darker skin color
Feeling of sadness or depression

Testing for Iron Overload

If your doctor suspects you have too much iron in your body, they can usually confirm this with simple, affordable blood tests. However, blood iron levels aren’t a helpful indication of this. High levels of serum ferritin, which is a blood cell protein that contains iron, can suggest an iron overload. But, keep in mind, serum ferritin levels can also go up for different reasons, such as inflammation, an infection, or a liver disease.

Your doctor may also check the percentage of iron in your blood that’s bound to a protein called transferrin. If this number is greater than 45%, it may help support the diagnosis of iron overload. In typical cases of a condition called hemochromatosis, which causes iron overload, both serum ferritin and transferrin iron saturation percentages will likely be high.

We can also use a method called Magnetic Resonance Imaging (MRI) to measure how much iron is in your body. This test is particularly useful to check the amount of iron in the liver and spleen. If the MRI shows a significant amount of iron just in the liver and not much in the spleen, it’s likely due to a deficiency of a hormone called hepcidin.

If the blood tests and imaging show that you have iron overload, your doctor might suggest genetic testing to confirm the diagnosis. One specific gene, known as the HFE gene, is typically associated with hemochromatosis. There are several ways this gene can be mutated, and individuals with specific mutation patterns (like C282Y/C282Y, H63D/H63D, or C282Y/H63D) are at a higher risk for the disease. Genetic testing isn’t always available widely as it needs specialized labs. So, treatment isn’t dependent on knowing the exact gene mutation, and it shouldn’t be delayed once the doctor confirms the presence of iron overload in the body.

In rare, complex cases, your doctor might suggest a liver biopsy to determine the iron levels. This procedure involves taking a small tissue sample from your liver, and it carries more risk than simple blood testing. However, the use of liver biopsies has dropped over time thanks to less invasive testing methods.

Once it’s confirmed that you have an iron overload, your doctor might conduct more specific tests based on the suspected affected organ.

Treatment Options for Iron Overload

Iron overload, a medical condition that occurs when too much iron builds up in your body, is typically treated using a process called reduction therapy. The most common method involves therapeutic phlebotomy, which is just a fancy way of saying medically supervised blood removal. This is done repeatedly, every 1 to 2 weeks initially, to help lower iron levels. When the iron level, also known as serum ferritin, becomes too high (over 1000 ng/ml), it can cause liver damage and shorten life expectancy.

For people whose iron levels are slightly elevated, doctors often recommend regular blood donation. However, donating blood more than once every eight weeks usually requires doctor’s approval.

If a patient’s health, specifically their hemoglobin level, can’t tolerate therapeutic phlebotomy, another treatment called iron chelation therapy is considered. This involves drugs like deferoxamine (administered via prolonged infusions), deferasirox, or deferiprone. These medicines help rid the body of excess iron. Deferoxamine can sometimes cause side effects like low blood pressure, dizziness, rash, and increased risks for certain specific infections and lung conditions. Deferasirox and deferiprone are newer treatments, offered in pill form, which might be just as effective as deferoxamine, but are easier to take.

Another way to help patients suffering from iron overload, specifically a type of hereditary iron overload condition known as hemochromatosis, is the use of a medication called pantoprazole. This belongs to a class of drugs known as proton pump inhibitors and has been shown in studies to help reduce the need for blood removal treatments in patients with a specific type of genetic mutation (C282Y).

Researchers are also looking into treatments centered around a protein in your body called hepcidin.

Patients undergoing treatment for iron overload are advised to avoid taking iron supplements, vitamins that contain iron, and vitamin C, as these can increase iron levels in the body.

When a doctor suspects hemochromatosis, a condition caused by too much iron in the body, they may examine different potential causes. These might include:

High iron levels due to frequent blood transfusions
Overconsumption of iron
Alcoholic liver disease
Abnormal production of red blood cells in the bone marrow
High iron levels coupled with chronic anemia
A condition called porphyria cutanea tarda

In such cases, performing a genetic test for the HFE gene or other related mutations can provide insights for a potential diagnosis.

Another condition related to excess iron in the body is called neuroferritinopathy. This is caused by a genetic mutation in the FTL gene. It leads to a buildup of iron in specific parts of the brain called the basal ganglia. Symptoms may include involuntary movements, muscle contractions, and difficulty with speech and swallowing. Over time, it may also lead to behavioral changes and issues with thinking and understanding.

What to expect with Iron Overload

However, if left untreated or not treated adequately, these patients face a lower survival rate. They are more likely to develop serious health problems such as liver cirrhosis (scarring of the liver), hepatocellular carcinoma (a type of liver cancer), pancreatic fibrosis (scarring of the pancreas), and diabetes. The level of iron at the time of diagnosis is also crucial in determining their health outlook. Patients with a ferritin level (a blood protein containing iron) above 2000 ug/L have higher mortality rates compared to those with a ferritin level below 1000 ug/L.

For patients facing severe liver damage due to inadequate treatment of their hemochromatosis, a liver transplant can be an effective solution. This is essentially a cure because the new liver will have the normal HFE genotype, which results in normal hepcidin production (a hormone that helps to regulate iron). Those with serious heart problems related to their HFE gene mutation may also consider a heart transplant.

Possible Complications When Diagnosed with Iron Overload

When a person’s body has too much iron, it can cause serious health problems. Having an excess of iron in important organs like the liver, heart, and endocrine glands (the glands that produce hormones) can cause damage to these organs as it forms harmful reactive oxygen species. This iron overload can result in a variety of issues including:

Liver diseases, such as cirrhosis (scarring of the liver) and hepatocellular carcinoma (a type of liver cancer)
Heart conditions, also known as cardiomyopathies
Endocrine disorders like diabetes and hypothyroidism (underactive thyroid)
Infections, due to an impaired immune response

If these complications arising from too much iron in the body are recognized and managed, it can help prevent further deterioration of the organ function and improve a patient’s overall health outcomes. Regular check-ups, proactive interventions, and collaboration among various medical disciplines are key to handling the issues caused by excessive iron accumulation.

Preventing Iron Overload

Preventing too much iron build up in your body, known as iron overload, focuses on recognizing and controlling the risk factors related to this condition. Regular check-ups are especially important for people more likely to experience this, such as those who are genetically prone to it or who need frequent blood transfusions. Early discovery can make a big difference.

It’s also essential to get tested for a genetic condition called hereditary hemochromatosis, which could cause iron overload, and to regularly monitor your iron levels as part of your preventive care routine.

Your healthcare provider plays a critical role in teaching you about the possible risks of having too much iron in your body. They also highlight the importance of having a balanced diet and advise against unnecessary iron supplements.

For patients who might be prone to secondary iron overload, doctors must carefully handle iron treatments. This means using transfusions wisely and closely watching how much iron you’re getting from your diet. This proactive approach to identifying and dealing with the factors that could lead to iron overload is the foundation for effective prevention. It helps reduce the chances of damage to your organs and improves overall health outcomes.

Frequently asked questions

Iron overload is a condition where there is an excessive buildup of iron in the body, which can lead to damage in organs such as the liver, heart, and endocrine glands. It can be caused by genetic mutations, blood transfusions, breakdown of red blood cells, or consuming too much iron in the diet.

It is estimated that around 16 million Americans have iron overload, either due to inherited conditions or other causes.

The signs and symptoms of iron overload, also known as hemochromatosis, can vary from person to person. However, some common signs and symptoms include: - Feeling constantly tired: Fatigue and a lack of energy are common symptoms of iron overload. This can be due to the excess iron affecting the body's ability to produce energy. - Joint pain: Iron overload can cause joint pain and stiffness, particularly in the hands and fingers. This can make it difficult to perform everyday tasks and can affect quality of life. - Belly pain: Some individuals with iron overload may experience abdominal pain or discomfort. This can be caused by the excess iron accumulating in the liver or other organs. - Enlarged liver: Iron overload can lead to the liver becoming enlarged. This can cause discomfort or pain in the upper right side of the abdomen. - Irregular heartbeat: Iron overload can affect the heart, leading to an irregular heartbeat or palpitations. This can be a serious symptom and should be evaluated by a healthcare professional. - Lower sex drive: In some cases, iron overload can lead to a decrease in sex drive or sexual dysfunction. This can be due to the impact of excess iron on hormone levels and overall health. - High blood sugar levels: Iron overload can affect the body's ability to regulate blood sugar levels, leading to higher than normal levels. This can increase the risk of developing diabetes or worsen existing diabetes. - Darker skin color: Excess iron can cause a darkening of the skin, particularly in areas such as the face, neck, and underarms. This is known as hyperpigmentation. - Feeling of sadness or depression: Iron overload can have an impact on mental health, leading to feelings of sadness, depression, or mood swings. This can be due to the effects of excess iron on brain function and neurotransmitter levels. It's important to note that not everyone with iron overload will experience all of these symptoms, and some individuals may not have any symptoms at all. If you suspect you may have iron overload, it's important to speak with a healthcare professional for proper diagnosis and management.

You can get iron overload through inheritance, blood transfusions, having too much iron in your diet, or processes within the body that destroy red blood cells.

The other conditions that a doctor needs to rule out when diagnosing Iron Overload are: 1. High iron levels due to frequent blood transfusions. 2. Overconsumption of iron. 3. Alcoholic liver disease. 4. Abnormal production of red blood cells in the bone marrow. 5. High iron levels coupled with chronic anemia. 6. A condition called porphyria cutanea tarda.

The types of tests that are needed for Iron Overload include: - Blood tests to measure serum ferritin levels and the percentage of iron bound to transferrin. - Magnetic Resonance Imaging (MRI) to measure the amount of iron in the liver and spleen. - Genetic testing to check for mutations in the HFE gene associated with hemochromatosis. - In rare cases, a liver biopsy may be suggested to determine iron levels. - Additional specific tests may be conducted based on the suspected affected organ.

Iron overload is typically treated using a process called reduction therapy. The most common method is therapeutic phlebotomy, which involves medically supervised blood removal. This is done repeatedly, initially every 1 to 2 weeks, to help lower iron levels. For people with slightly elevated iron levels, regular blood donation is often recommended. If therapeutic phlebotomy is not suitable, iron chelation therapy with medications like deferoxamine, deferasirox, or deferiprone may be considered. Pantoprazole, a proton pump inhibitor, has also been shown to help reduce the need for blood removal treatments in patients with a specific genetic mutation.

When treating Iron Overload, there can be side effects associated with the different treatment methods. Here are the potential side effects: - Therapeutic phlebotomy (medically supervised blood removal): - No specific side effects mentioned in the text. - Iron chelation therapy (using drugs like deferoxamine, deferasirox, or deferiprone): - Deferoxamine: low blood pressure, dizziness, rash, increased risks for certain specific infections and lung conditions. - Deferasirox and deferiprone: No specific side effects mentioned in the text. - Pantoprazole (medication for hereditary iron overload condition): - No specific side effects mentioned in the text. It's important to note that the text does not provide an exhaustive list of side effects, and individual experiences may vary. It is recommended to consult with a healthcare professional for more information about potential side effects and to discuss any concerns.

Patients with iron overload, also known as hemochromatosis, generally have a highly positive outlook if diagnosed early and treated effectively to manage iron levels within an acceptable range. These patients tend to live as long as those without the condition and have extremely low chances of suffering from liver damage if they keep their iron levels in check. However, if left untreated or not treated adequately, these patients face a lower survival rate and are more likely to develop serious health problems such as liver cirrhosis, liver cancer, pancreatic fibrosis, and diabetes.

You should see a healthcare provider or doctor for iron overload.

Medications