What Is Haemochromatosis?

Haemochromatosis is an inherited condition where iron accumulates in a person's organs and leads to organ damage. It is an autosomal recessive condition, meaning both parents of an individual have to have a mutation of the involved gene for their child to inherit the disease. Haemochromatosis is most common in people of Northern European descent.

Overview

This article explains hereditary haemochromatosis, a genetic disorder that causes excessive iron absorption. We will explore the causes, symptoms, and potential complications of this condition. Additionally, we offer insights into diagnosis, treatment options, and lifestyle modifications that can help in the effective management of the disease.

Causes of haemochromatosis

Haemochromatosis is caused by mutations in several variants of the HFE gene (coding for an iron regulatory protein expressed on the surface of liver and intestinal cells). Some of the variants of the HFE gene that have been implicated in haemochromatosis are mutations in the HFE gene, C282Y, and H63D.¹

Signs and symptoms of haemochromatosis

Haemochromatosis is a disease of iron overload and while not all people with the disease show outward signs of disease, the signs, and symptoms that manifest depend on the degree of iron overload and the organ affected.

Cirrhosis

About 70% of people with haemochromatosis have liver damage due to excess iron deposition, leading to scarring of the liver (cirrhosis). They also have a greater risk of liver cancer (hepatocellular carcinoma).²

Arthropathy 

Arthropathy, or joint disease, in haemochromatosis is caused by the accumulation of iron in the joint spaces. This leads to joint pain that is most commonly seen in the joints of the knees, back, wrists, and neck.²

Diabetes 

Accumulation of iron in the pancreas leads to the destruction of the organ and loss of its ability to produce insulin, a hormone that regulates sugar levels in the blood. This results in consistently high levels of sugar in the blood and eventually diabetes mellitus.²

Skin changes 

Hyperpigmentation is a typical sign of haemochromatosis that is part of the classic triad of diabetes mellitus, skin pigmentation, and liver cirrhosis that occurs late in the disease when iron levels are very high in the body.²

Cardiomyopathy 

Deposition of iron in the heart leads to enlargement of the heart and diseases like congestive heart failure. The increased size of the organ may also affect the conduction system of the heart and lead to arrhythmias (irregular heart rhythms).²

Impotence and hypogonadism

Hypogonadism which manifests as impotence in people assigned males at birth (AMAB) as well as loss of libido, and loss of menstrual periods in people assigned females at birth (AFAB) are common symptoms seen in patients with hereditary haemochromatosis. The loss of periods that can occur in AFAB is less frequent than hypogonadism in AMAB. This is a result of iron deposition in the pituitary gland which is an organ responsible for secreting most of the hormones responsible for sexual development and function.²

Diagnosis of haemochromatosis

Blood tests: The blood tests that help to diagnose haemochromatosis include:²

• Liver enzymes: usually elevated
• Transferrin saturation level: above 200 mcg/L in AFAB, and 300 mcg/L in AMAB
• Serum ferritin level: more than 40% in AFAB, and 50% in AMAB

Genetic testing: Genetic tests are used for diagnosis of the disease and screening for asymptomatic patients. It is also used to screen patients with liver disease that show evidence of iron overload.

Imaging Studies: X-rays and echocardiography are used to demonstrate the heart enlargement caused by haemochromatosis. CT scans are sometimes used but are not very sensitive for diagnosing the disease. MRI scans of the liver are useful to measure liver damage by iron deposition.²

Biopsy: This entails taking parts of possibly affected organs like the skin or liver to analyse under the microscope and to test for excess iron.

Management and treatment for haemochromatosis

Phlebotomy: This is the process of removing blood from a person’s vein using a needle, which removes excess iron from the body and when done at regular intervals, helps maintain normal levels of iron.³ The frequency of this treatment is guided by the individual’s ferritin levels. Ferritin is a protein in the blood that stores iron and releases it as the body needs it. Its levels are an indicator of the amount of iron in the body.

Surgery: Surgery is often used to treat severe joint disease and end-stage liver disease. A liver transplant is required to treat patients who develop the complication of hepatocellular carcinoma (the most common type of primary liver cancer).² If there is severe joint destruction, surgical removal and replacement of the affected joint are considered.

Chelation therapy: This is when ions that can bind iron and form compounds that prevent iron from being absorbed in the intestines are used. The compound formed is then expelled from the body through faeces. This treatment is most preferred for people with anaemia who cannot be treated with phlebotomy. Deferoxamin, deferiprone, and deferasirox are some of these iron-chelating agents.²

Dietary modifications: Individuals with haemochromatosis are advised not to consume foods that contain large amounts of iron like red meat or organ meats. Supplements like Iron supplements and vitamin C supplements should be avoided. Vitamin C makes iron more easily absorbed by the body. Alcohol abuse is discouraged as this might compound the liver damage caused by the disease. Simultaneously, ethanol has also been shown to increase iron absorption.²

Risk factors

It has been noted to be more prevalent in people of Northern European descent with a higher rate in people of Celtic origin. It is 6 times higher in Caucasians than in people of other races. AMAB are affected almost 2-3 times more than AFAB. The disease also becomes more apparent at about age 40 for AMAB and over age 50 for AFAB. It is thought that AFAB present with symptoms later in life because of iron loss associated with menstruation. People with diseases that require multiple transfusions are at risk for iron overload and haemochromatosis.

Complications

• Liver cirrhosis and hepatocellular carcinoma
• Heart failure
• Diabetes
• Hypogonadism and impotence
• Arthritis

FAQs

Can haemochromatosis be prevented?

Haemochromatosis is an autosomal recessive genetic disease. The main way to prevent the disease is genetic testing, especially for people who have first-degree relatives with the disease or known carriers. The secondary form of the disease which may be caused by repeated transfusions done for the treatment of other diseases like sickle cell anemia and thalassemia can be prevented by regulating the number of transfusions done and combining them with other non-transfusion blood-boosting treatments. Administration of iron chelating treatments to people who have to undergo regular transfusions is another preventive measure.

How common is haemochromatosis?

It is difficult to estimate the number of people that are affected by the disease. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) estimates that about 1 in 15 people of Northern European ancestry have one copy of the C282Y mutation in the HFE gene. This proposes that about 1 in 225 people in this population are likely to have two copies of the gene and are at risk of developing haemochromatosis. In the United States, about 1 in 300 Caucasian people have hereditary haemochromatosis.

When should I see a doctor?

You should see a doctor for an evaluation if you have a family history of haemochromatosis or are concerned that you may have the disease. Some common early signs of haemochromatosis are weakness and fatigue, low libido, skin darkening, joint pain, and joint stiffness.

Summary

Haemochromatosis is a genetic disease characterised by the accumulation of iron in organs of the body which results in damage and impaired function of those organs. The disease is caused by the mutation of a gene called the HFE gene. Symptoms of the disease depend on the organ affected and the severity of damage to the organ. They range from hair, skin, and nail abnormalities, to liver and heart problems and diabetes. It is diagnosed by carrying out blood and imaging tests and taking samples of some of the organs affected for testing. Consequently, treatment is also dependent on the severity of the disease and the organ affected. Regular removal of blood through phlebotomy to decrease excess iron, chelation therapy with iron-binding drugs, and surgery for complications like liver disease and arthritis are all treatments used for patients with haemochromatosis. It predominantly affects individuals of Northern European descent and affects more AMAB than AFAB. Early diagnosis of the disease, especially by screening people with affected relatives goes a long way in preventing the potentially deadly complications that might result from it.