What is Hemochromatosis (Bronze Diabetes)?
Hemochromatosis is a condition that happens when too much iron builds up in the body, which can damage multiple organs. The body usually controls the amount of iron it takes up, as it can’t get rid of any extra iron. When there’s a dangerous amount of iron stored in the body, it’s known as hemochromatosis.
This condition is often referred to as “bronze diabetes” because it can change the color of the skin and cause problems with the pancreas. There are two types of this disease, hereditary and secondary hemochromatosis.
Hereditary hemochromatosis is a genetic condition, meaning it’s passed down through families. It’s the most common type of genetic disorder that involves both copies of a gene in each cell being altered, specifically among white people.
Secondary hemochromatosis usually develops as a result of disorders that involve the production of red blood cells and treatments involving blood transfusions. This happens because when the transfused red blood cells get damaged, the iron in them gets stored in the body. Conditions that can cause secondary hemochromatosis include thalassemia, sickle cell anemia, hereditary spherocytosis, X-linked sideroblastic anemia, and pyruvate kinase deficiency.
What Causes Hemochromatosis (Bronze Diabetes)?
In hereditary hemochromatosis, a condition caused by an inherited defect, excess iron tends to get stored mainly in the body’s tissue cells. In transfusional hemochromatosis, which is caused by frequent blood transfusions, the surplus iron usually collects in what we call reticuloendothelial cells. These are a broad group of cells involved in immune response and repairing tissue.
This extra iron is stored as a substance called hemosiderin (iron-storage complex). Over time, the build-up of hemosiderin can lead to cell death. As these cells die, they’re replaced by fibrous tissue, causing damage to or failure of the affected organ.
Hereditary hemochromatosis is caused by a mutation in the hemochromatosis gene (HFE protein). The HFE gene helps regulate the amount of iron absorbed from the diet. When this HFE gene mutation occurs, your body absorbs more iron than it needs even though you are consuming a normal amount of iron in food. There are two common types of these mutations known as C282Y and H63D. The HFE gene is located on a section known as 6p21.3 in chromosome 6 (one of the structures that carry genes).
There are different forms of hereditary hemochromatosis:
1. Type 1 (HFE-related): This is the classic form of this condition. It’s inherited, which means it’s passed down from parents to their children. This type is quite common worldwide.
2. Type 2a (caused by mutations of the hemojuvelin gene) and type 2b (mutations of the hepcidin gene): These are conditions passed down in families that affect both white and non-white individuals. The symptoms typically begin appearing when individuals are aged 15 to 20 years.
3. Type 3 (due to mutations of the transferrin receptor-2 gene): This is also an inherited condition that affects white and non-white individuals, typically starting to show signs at ages 30 to 40 years.
4. Type 4 (caused by mutations of the ferroportin gene): This is a hereditary disease that comes out at any age between 10 and 80 years and also affects white and non-white individuals. It’s unique in that it’s an autosomal dominant disease, meaning you only need to inherit the gene from one parent to develop the condition.
Risk Factors and Frequency for Hemochromatosis (Bronze Diabetes)
Hereditary hemochromatosis is a genetic disorder that is most commonly found in white people, with 1 in 300 to 500 individuals affected by the condition. It is seen all around the world, but type 1 is particularly found in people of northern European ancestry. The disease has the same prevalence rate in Europe, Australia, and other Western countries, and is especially common amongst people of Celtic origin. Conversely, it is less common in people of African descent, with the white population having a six times greater risk of developing the disease than black people.
- Men are more likely to be affected by hemochromatosis than women, with 2-3 males affected for every female.
- The estimated ratio of men to women with this condition is between 1.8:1 and 3:1.
- Women tend to show symptoms of hemochromatosis later in life than men. This is because the blood loss and iron excretion that come with menstruation can delay the onset of symptoms.
- In men, the disease usually begins to show symptoms in their fifties.
- In women, the disease often presents in their sixties.
- However, juvenile hemochromatosis can appear in people aged between 10 and 30.
Signs and Symptoms of Hemochromatosis (Bronze Diabetes)
Hemochromatosis is a medical condition that most often doesn’t show symptoms until adults have damage in several organs. Interestingly, the symptoms people experience are usually linked to the specific organ that is affected. However, almost all patients note feeling very tired. Usually, symptoms are present for up to ten years before a diagnosis is made. Accurately diagnosing this condition requires a careful investigation of the patient’s family health history. Women tend to show symptoms later in life than men because menstruation leads to blood loss which helps to get rid of excess iron.
Early symptoms may include joint pain, fatigue, and feeling sluggish. There can also be signs that are noticeable only at a later stage, once iron starts building up in the tissue:
- Koilonychia: A condition affecting the nails, mostly the thumb and index finger, found in half of the patients. In one-fourth of the patients, it may affect all the nails.
- Secondary diabetes: Signs of this can often be detected through examining the sides of the fingers for marks signifying diabetes, and the belly for signs of insulin administration.
- Skin discoloration: More than 90% of patients with this disease experience changes in their skin color; it’s particularly noticeable in parts of the skin that get a lot of sun. Skin may also display dryness and thinning, especially on the front of the legs.
The buildup of calcium crystals in the joints (pseudogout) can cause joint pain, chondrocalcinosis (calcification in the cartilage), and swelling. This is most commonly seen in the finger and toe joints, but also knees, wrists, hips, back, neck, and feet. Liver complications might also be present, with or without the yellowing of the skin and eyes (jaundice), including abdominal pain, enlarged liver, cirrhosis or scarring of the liver, elevated blood pressure in the liver’s blood vessels (portal hypertension), fluid buildup in the abdomen (ascites), and enlarged spleen. While cirrhosis only affects 10-15% of patients, the chance of liver cancer (HCC) increases, particularly in patients who have both hemochromatosis and cirrhosis. This is true for up to 30% of patients.
Additional complications may include heart problems, such as restrictive or dilated cardiomyopathy, arrhythmias, and heart failure. Endocrine dysfunction can also occur, leading to conditions like diabetes, hypogonadism (resulting in decreased sex drive and impotence in men, menstrual irregularities in women), pituitary and adrenal dysfunction, thyroid and parathyroid defects, and osteoporosis. Gynecomastia (enlargement of breasts) and decreased body hair can occur due to both chronic liver disease and hypogonadism. Partial to complete hair loss is seen in some patients, usually around the pubic area.
Finally, patients with hemochromatosis have a 20 times greater risk of liver cancer compared to the general population. They are also more susceptible to infection from certain bacteria, including Yersinia enterocolitica, Listeria monocytogenes, and Vibrio vulnificus.
Testing for Hemochromatosis (Bronze Diabetes)
The first steps to identify hemochromatosis, a disease of excessive iron in the body, usually involve blood tests to measure serum transferrin saturation or serum ferritin concentration. However, transferrin saturation testing might not be as reliable for checking iron overload in certain types of hemochromatosis. And inflammatory conditions may impact the accuracy of ferritin testing. If a woman has a ferritin level above 200 mcg/L or a man above 300 mcg/L, or if transferrin saturation is more than 40% in women or 50% in men, more tests might be needed.
In the U.S., where the HFE mutation causing hemochromatosis is common, genetic tests for C282Y and H63D mutations can be done. These tests can confirm over 90% of hemochromatosis cases.
Imaging techniques like echocardiography and chest x-rays can help identify if heart or lungs are affected. MRI of the liver is a non-invasive method to check for iron accumulation in the liver.
If necessary, a liver biopsy might be performed. This test can measure liver iron content accurately and reveal any liver damage. Under microscopic analysis, the iron deposits usually affect liver cells and bile duct cells specifically, with only minor impact on Kupffer cells, the cleaning crew of the liver.
Liver biopsy is typically used when a person diagnosed with hemochromatosis has high liver enzyme levels or serum ferritin levels above 1000 mcg/L. It’s also common for a patient with hemochromatosis to have increased liver enzymes, often doubled from normal levels.
It’s also crucial to check fasting blood sugar levels for any signs of diabetes. Other tests include an echocardiogram to check the heart, hormone levels to assess for reduced sexual function or other hormone issues, and bone densitometry to check for osteoporosis. Quite often, a high blood glucose (blood sugar) test result can signal diabetes, but the standard test for long-term blood sugar control — the HbA1c test — may not be reliable in patients who have high turnover of red blood cells.
If a patient is diagnosed with hemochromatosis, their close family members should also be checked for the disease through genetic testing.
Treatment Options for Hemochromatosis (Bronze Diabetes)
For treating primary hemochromatosis, a condition where the body stores too much iron, the usual method is phlebotomy, which is removing blood from the body. Red blood cells in our body contain a large amount of iron, so drawing out these cells can reduce iron levels and lessen harm caused by iron overload. A large number of phlebotomies will be needed to bring the iron levels back to normal, usually done once or twice a week. Once the iron levels are normal, a patient still needs to continue with phlebotomy, albeit less frequently, for life. The aim of this treatment is to keep ferritin, a protein that stores iron, at lower levels. This treatment can reduce issues like skin darkening, fatigue, and insulin sensitivity. However, it doesn’t change already existing cirrhosis, hypogonadism, and arthropathy, which are diseases of the liver, reproductive glands, and joints, respectively.
Many recommend completely stopping alcohol consumption for those with primary hemochromatosis as alcohol can increase liver and pancreas damage. Though phlebotomy might not reverse existing organ damage in patients, it can help manage any symptoms stemming from organ dysfunction, like administering insulin for pancreatic dysfunction. If detected early enough, treating primary hemochromatosis can prevent further damage to organs. However, if significant organ damage has occurred before diagnosis, life expectancy is typically short.
Chelation therapy, which involves using medication to remove excess iron from your body, although not as helpful in hereditary hemochromatosis, can be beneficial for erythropoietic hemochromatosis, a different type of iron overload disorder. In this disorder, phlebotomy is usually not an option. There are iron-chelating agents available to bind iron in the body and help remove it through urine or stool. These agents can be injected or taken orally, and all have similar effectiveness.
Sometimes, patients with primary hemochromatosis might also receive erythropoietin, a hormone that aids red blood cell production alongside phlebotomy. This treatment helps maintain the concentration of hemoglobin, a protein in red blood cells, while iron is being removed from the body.
If patients have severe, end-stage liver disease due to iron overload, they might be evaluated for a liver transplant. However, research indicates that patients with iron overload disorders who undergo liver transplantation generally have lower survival rates compared to other patients receiving liver transplants.
Due to the risk of hepatocellular carcinoma (HCC), a type of liver cancer, which responsible for about 30% of deaths in primary hemochromatosis, all those affected with this condition are advised to undertake regular checkups. This usually includes ultrasounds and alpha-fetoprotein level checks every six months, helping in early detection and treatment of any potential issues.
What else can Hemochromatosis (Bronze Diabetes) be?
Hemochromatosis, a condition that affects multiple organ systems, can often be confused with other diseases. Here are some conditions that may have similar symptoms:
- Iron overload due to frequent blood transfusions
- Hepatitis B and C
- Nonalcoholic fatty liver disease (NAFLD)
- Overconsumption of iron supplements
- Dysmetabolic hyperferritinemia, a metabolic disorder
- Hereditary aceruloplasminemia, a genetic disorder
- Alcoholic liver disease
- Porphyria cutanea tarda, a specific type of porphyria
- Marrow hyperplasia or excessive bone marrow growth
- Hemolytic anemia, a blood condition
- Biliary cirrhosis, a type of liver disease
What to expect with Hemochromatosis (Bronze Diabetes)
If left untreated, the disease can progress and cause severe damage to the liver. This can result in cirrhosis, a form of liver disease, hepatocellular carcinoma which is a type of liver cancer, and other complications caused by too much iron in the tissues and organs. However, due to advancements in our ability to diagnose and manage this condition, the chances of recovering and living a healthy life have improved over the last few decades.
The primary factor considered when determining the outlook for a patient is hepatic fibrosis or cirrhosis; these are both types of liver disease. An early diagnosis and regular treatment using phlebotomy, which is a procedure that removes some of your blood, can decrease most of the complications associated with this condition, known as hemochromatosis.
Possible Complications When Diagnosed with Hemochromatosis (Bronze Diabetes)
Patients become more susceptible to a liver disease called cirrhosis if they also suffer from alcoholism or hepatitis. There can also be other problems associated with this, including:
- Liver cancer
- Diabetes
- Heart disease
- Lower levels of sex hormones
- Bone loss or weakened bones, known as osteoporosis
- Increased risk of infection from certain types of bacteria for patients with excess iron in their bodies
Preventing Hemochromatosis (Bronze Diabetes)
Patients should be informed that consistently getting phlebotomy treatment (removal of blood) and using special medicines called “chelating agents” can help avoid most issues related to a condition known as hemochromatosis. It’s crucial to steer clear of alcohol consumption. Additionally, patients are advised to refrain from taking any supplements containing iron or vitamin C. People with hemochromatosis do not need to follow any specific diet, though.
