Hemochromatosis - Not a rare disease

Hemochromatosis is a disease in which too much iron builds up in the body. This is also called iron overload. Accumulation of iron in the organs is toxic and can cause organ damage. While many organs can be affected, iron overload is especially likely to affect the liver, heart, and pancreas.

Too much iron in the liver can cause an enlarged liver, liver failure, liver cancer, or cirrhosis (sir-RO-sis). Cirrhosis is scarring of the liver, which causes the organ to not work well.

Too much iron in the heart can cause irregular heartbeats called arrhythmias (ah-RITH-me-ahs) and heart failure. Too much iron in the pancreas can lead to diabetes.

If hemochromatosis isn't treated, it may even cause death. File:Hemochromatosis.webm

Types

Hereditary hemochromatosis Hemochromatosis may be hereditary, meaning it is caused by genetic changes (mutations or pathogenic variants) to any of several genes including FTH1, HAMP, HFE, HFE2 (also known as HJV), SLC40A1, and TFR2.Hereditary hemochromatosis is classified by type based on age of onset, genetic cause, and mode of inheritance:

• Hemochromatosis type 1
• Hemochromatosis type 2
• Hemochromatosis type 3
• Hemochromatosis type 4
• Hemochromatosis type 5

Acquired hemochromatosis In other cases, hemochromatosis develops as a side-effect or symptom of another disease such as anemia, chronic liver disease, or an infection. This is called acquired hemochromatosis.

Neonatal hemochromatosis When hemochromatosis develops in an infant and the exact cause of the disease cannot be determined, it is called neonatal hemochromatosis.

Cause

The cause of hemochromatosis depends on whether a person has a hereditary form, an acquired form, or the neonatal form. Hereditary hemochromatosis is caused by genetic changes (mutations or pathogenic variants) in any of several genes:

• Hemochromatosis type 1 is caused by pathogenic variants in the HFE gene
• Hemochromatosis type 2 is caused by pathogenic variants in the HFE2 (HJV) or HAMP genes
• Hemochromatosis type 3 is caused by pathogenic variants in the TFR2 gene
• Hemochromatosis type 4 is caused by pathogenic variants in the SLC40A1 gene
• Hemochromatosis type 5 is caused by pathogenic variants in the FTH1 gene

These genes all provide the body with instructions to make proteins that help regulate how iron is absorbed from the diet, transported, and stored. Pathogenic variants in these genes cause changes in how iron is absorbed and distributed throughout the body. This causes iron to accumulate in tissues and organs, which can cause organ damage.

Acquired hemochromatosis is usually a symptom of other blood-related disorders such as thalassemia or certain anemias. Acquired hemochromatosis can also be caused by having many blood transfusions or long-term alcohol use. The cause of neonatal hemochromatosis is not fully understood. However, a woman with an affected child has approximately an 80% chance to have another affected child. This form of hemochromatosis appears to run in families, but the exact cause is unknown.

Inheritance

Hereditary hemochromatosis is inherited in an autosomal recessive or autosomal dominant manner, depending on which type a person has.

Hemochromatosis types 1, 2, and 3 are inherited in an autosomal recessive manner.This means that people with these types of hemochromatosis have a genetic change (mutation or pathogenic variant) in both copies of a gene causing hemochromatosis in each cell of the body. We inherit one copy of every gene from our mother and the other from our father. The parents of a person with hemochromatosis types 1, 2, or 3 are each expected to have one changed copy of the gene causing hemochromatosis. People with one changed copy of a gene are known as carriers. Carriers typically do not have signs or symptoms of hemochromatosis.

When two carriers of an autosomal recessive form of hemochromatosis have children, each child has a: 25% chance to have hemochromatosis 50% chance to be a carrier like each parent 25% chance to have two working copies of the genes causing hemochromatosis, meaning the child is unaffected and is not a carrier

Hemochromatosis types 4 and 5 are inherited in an autosomal dominant manner. People with these types of hemochromatosis have one changed copy of the SLC40A1 gene or FTH1 genes. In most cases, people with these types of hemochromatosis inherit the genetic change from a parent who also has the disease. When a person with an autosomal dominant type of hemochromatosis has children, each child has a: 50% to inherit hemochromatosis 50% chance to be unaffected Acquired hemochromatosis is not inherited and is not thought to run in families. Neonatal hemochromatosis is thought to run in families, but the exact cause is not well understood.

Risk factors

Hemochromatosis is one of the most common genetic diseases in the United States. It's most common in Caucasians of Northern European descent. The disease is less common in African Americans, Hispanics, Asians, and American Indians.

Primary hemochromatosis is more common in men than in women. Also, older people are more likely to develop the disease than younger people. In fact, signs and symptoms usually don't occur in men until they're 40 to 60 years old.

In women, signs and symptoms usually don't occur until after the age of 50 (after menopause). Young children rarely develop hemochromatosis.

Inheriting two faulty HFE genes (one from each parent) is the major risk factor for hemochromatosis. However, many people who have two copies of the faulty gene don't develop signs or symptoms of the disease.

Alcoholism is another risk factor for hemochromatosis. A family history of certain diseases and conditions also puts you at higher risk for hemochromatosis. Examples of such diseases and conditions include heart attack, liver disease, diabetes, arthritis, and erectile dysfunction (impotence).

Signs and symptoms

Hemochromatosis can affect many parts of the body and cause various signs and symptoms. Many of the signs and symptoms are similar to those of other diseases.

Signs and symptoms of hemochromatosis usually don't occur until middle age. Women are more likely to have general symptoms first, such as fatigue (tiredness). In men, complications such as diabetes or cirrhosis (scarring of the liver) often are the first signs of the disease.

Signs and symptoms also vary based on the severity of the disease. Common signs and symptoms of hemochromatosis include joint pain, fatigue, general weakness, weight loss, and stomach pain.

Not everyone who has hemochromatosis has signs or symptoms of the disease. Estimates of how many people develop signs and symptoms vary greatly. Some estimates suggest that as many as half of all people who have the disease don't have signs or symptoms.

Hemochromatosis Complications If hemochromatosis isn't found and treated early, iron builds up in your body and can lead to:

• Liver disease, including an enlarged liver, liver failure, liver cancer, or cirrhosis (scarring of the liver)
• Heart problems, including arrhythmias (irregular heartbeats) and heart failure
• Diabetes, especially in people who have a family history of diabetes
• Joint damage and pain, including arthritis
• Reproductive organ failure, such as erectile dysfunction (impotence), shrinkage of the testicles, and loss of sex drive in men, and absence of the menstrual cycle and early menopause in women
• Changes in skin color that make the skin look gray or bronze
• Underactive pituitary and thyroid glands
• Damage to the adrenal glands

Diagnosis

A diagnosis of hemochromatosis is suspected when a doctor observes signs and symptoms of the disease. A doctor may decide to order laboratory tests including a liver biopsy, MRI, or blood test. The diagnosis can be confirmed with genetic testing.

Treatment Treatment for hemochromatosis may include reducing iron levels by removing blood (phlebotomy), iron chelation therapy, dietary changes, and treatment for complications of the disease. The goal of treatment is to reduce the amount of iron in the body to normal levels, prevent or delay organ damage from excess iron, and maintain normal amounts of iron throughout the lifetime.

Phlebotomy helps to remove excess iron from the body. Most people begin treatment with weekly therapeutic phlebotomy, although sometimes treatment is initially twice a week if iron levels are very elevated. Maintenance phlebotomy usually involves treatment every 2-4 months.Iron chelation therapy may be recommended for some people with hemochromatosis if they have other health issues. This involves removing excess iron using medications.

Dietary recommendations for people with hemochromatosis may include avoiding alcohol and red meat. People with hemochromatosis are not recommended to take iron or vitamin C supplements.

NIH genetic and rare disease info

• NIH info on Hemochromatosis - Not a rare disease

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