Iron overload disorders are a group of medical conditions which cause excess iron to be stored in the body. They include hereditary hemochromatosis, a genetic disorder in which the body of a person absorbs too much iron from foods and beverages.
The body can’t excrete excess iron, so it retains it in certain organs, including the liver , heart, and pancreas, which can cause organ damage. Diabetes can cause damage to the pancreas. Excess iron can also turn the skin into a bronze colour, without treatment.
Those with this condition get a good outlook with treatment. Treatments may include drawing blood to reduce iron levels in the body, and making dietary changes to reduce the intake of iron.
We look at the forms, causes , symptoms and treatment of iron overload disorder in this article.
What are iron overload disorders?
Where iron reserves are adequate in a healthy body, the intestines limit the absorption of this mineral from food and drink to prevent its levels from increasing too high.
People with iron overload disorders consume more iron from the diet or supplements than normal. The body can’t excrete the extra iron quickly enough and it keeps piling up. This is contained in organ tissue, primarily in the liver, and also in the heart and pancreas.
There are many forms of disorder with overloading iron. Hereditary hemochromatosis is a key genetic-component disorder. Individuals can also experience secondary hemochromatosis, which occurs as a result of another disorder or disease.
There are several types of iron overload disorder, each with different causes:
Primary hemochromatosis: A genetic mutation
One of the most common genetic disorders in the United States is inherited hemochromatosis, which people can also call primary or classical hemochromatosis. Not all suffering from the disease experiences symptoms.
This disorder often affects those who are white. Approximately 1 in 200 Caucasian people in the United States and Australia have hereditary hemochromatosis, and 10–14 percent of each of these populations carry genetic mutations, according to a 2018 study.
Hereditary hemochromatosis occurs in a gene called HFE, due to a mutation. This gene controlls how much iron the body absorbs. Two possible mutations are C282Y and H63D within the HFE gene.
In the U.S., most people with hereditary hemochromatosis inherited two copies of C282Y, one from the father’s mother and the other. An individual who inherits only one defective gene is uncertain about developing iron overload syndrome, but they will be a carrier, so they are likely to ingest more iron than normal.
If both parents are carriers, their child has a 1 in 4 chance of having two faulty genes, one from each parent. Some people with two copies of the C282Y mutation never get symptoms, however.
Others inherit one mutation C282Y and one mutation H63D. A small percentage of those people may experience signs of hemochromatosis. Inheriting two copies of H63D is rare, and research has not yet confirmed whether this may increase the risk of hemochromatosis.
Secondary hemochromatosis: The result of a condition
According to the National Heart , Lung, and Blood Institute (NHLBI), secondary hemochromatosis may result from certain kinds of anemia, such as thalassemia or chronic liver disease, such as chronic hepatitis C infection or liver disease associated with alcohol.
Blood transfusions, oral iron tablets, iron injections, or long-term dialysis of the kidney can also induce secondary hemochromatosis.
Juvenile hemochromatosis is a condition inherited from the defects in a gene called HJV. Iron builds up earlier in life, and symptoms occur between 15 and 30 years of age.
Symptoms include diabetes, and sexual development issues. That can be fatal without treatment.
For newborns with neonatal hemochromatosis, iron will accumulate in the liver so rapidly that either the baby is stillborn or it does not survive long after birth. Research suggests that the cause is not genetic. This may occur because the immune system of the mother produces antibodies which damage the fetal liver.
The below risk factors may increase the likelihood of an individual having hemochromatosis:
- Genetic factors: Having two copies of a faulty HFE gene is the main risk factor for hereditary hemochromatosis. The person inherits one copy of the mutated HFE gene from each parent. H refers to high, and FE means iron.
- Family history: A person with a parent, child, brother, or sister with hemochromatosis is more likely to have it.
- Ethnicity: According to the NHLBI, Caucasian people of Northern European descent have a higher risk of having the HFE gene mutation and of developing hemochromatosis. They note that it is less common in people of African American, Hispanic, Asian, and American Indian descent.
- Gender: Iron overload affects both males and females, although it may have a less significant effect on females. The reason for this is that most females regularly lose blood during menstruation, and blood loss reduces iron levels. Males may develop symptoms at the age of about 40–60 years, and females may have symptoms after menopause.
The signs and symptoms of iron overload disorder are mostly mild, and a source for 2019 states that people with iron overload have no symptoms in 3 out of 4 cases.
Signs typically do not occur after menopause until middle age or, in females. Individuals with hemochromatosis are less likely to experience symptoms nowadays, as diagnosis appears to occur earlier than in the past.
The major signs as the disease progresses include:
- tiredness or fatigue
- weight loss
- abdominal pain
- high blood sugar levels
- hyperpigmentation, or the skin turning a bronze color
- a loss of libido, or sex drive
- in males, reduction in the size of the testicles
- in females, reduced or absent menstruation
In time, the following conditions may develop:
- liver disease or cirrhosis (permanent scarring) of the liver
- enlargement of the liver
- heart disease
Hemochromatosis can be difficult to diagnose from symptoms, as these may overlap with other conditions’ symptoms. A doctor may decide to refer the person to a hepatologist or a cardiologist (heart specialist).
Some tests can be useful to help doctors identify hemochromatosis. Those include blood checks, liver checks, genetic testing, MRI scans.
Just before signs occur, two different types of blood tests may detect iron overload.
The saturation test for serum transferin tests the amount of iron that is bound to transferrin — a protein that holds iron in the blood. More than 45 percent of saturation values are too high.
The serum ferritin test measures just how much iron the body has stored. Knowing these levels helps a doctor diagnose a person during treatment, and monitor them.
Doctors need to conduct these blood tests, and for improved precision, they will need to repeat them, because certain factors may also boost levels of ferritin.
These are not routine blood tests, and doctors typically do them only if someone has a parent, infant, or hemochromatose sibling.
People can also undergo these examinations, however, if they have any of the following signs , symptoms, and conditions:
- elevated liver enzymes
- erectile dysfunction
- extreme tiredness
- heart disease
- joint disease
The results of these blood tests that indicate iron deficiency in people who drink excessive quantities of alcohol, or those who have had multiple blood transfusions or hepatitis C.
These additional tests can help confirm a hereditary hemochromatose diagnosis:
- genetic testing can determine whether the person carries the HFE gene.
- MRI scans to check iron levels in the liver
- a liver biopsy can determine iron levels in the liver and reveal any cirrhosis or other damage, but this test is less common nowadays
If a person is diagnosed and treated early, they should have a normal life expectancy. Nevertheless, they will have daily blood checks, and treatment usually lasts for life.
Several iron overload treatments exist for:
A regular treatment for removing iron-rich blood from the body is phlebotomy, or venesection.
It will usually have to take place regularly before rates return to normal. When iron levels build up again, the person will need to repeat the treatment.
How much, and how often, blood the doctor takes depends on:
- the person’s age and sex
- the person’s overall health
- the severity of the iron overload
During the early stages of the treatment, doctors can remove 1 pint of blood once or twice a week. They may then remove blood every 2–4 months after this.
Phlebotomy can not cure cirrhosis but symptoms such as nausea, stomach pain, and fatigue may improve. This can also improve respiratory function and pain in the joints.
To remove excess iron from the body, iron chelation therapy involves taking oral or injected medicine. Medications that contain a drug that will bind the excess iron until it is excreted by the body.
Although doctors do not want to prescribe this as a first-line hemochromatose therapy, it may be suitable for certain patients.
Dietary changes to limit iron intake can help reduce symptoms. Dietary changes can include:
- avoiding supplements that contain iron
- avoiding supplements that contain vitamin C, as this vitamin increases iron absorption
- reducing iron-rich and iron-fortified foods
- avoiding uncooked fish and shellfish
- limiting alcohol intake, as this can damage the liver
An accumulation of iron without treatment can lead to complications in the safety, such as:
- a higher chance of liver cancer relating to cirrhosis or hemochromatosis
- diabetes and associated complications
- congestive heart failure if too much iron builds up in the heart and the body cannot circulate enough blood
- irregular heart rhythms, or arrhythmias, leading to chest pain, palpitations, and dizziness
- endocrine problems, such as hypothyroidism or hypogonadism
- arthritis, osteoarthritis, or osteoporosis
- bronze or gray skin due to the deposits of iron in skin cells
According to the Iron Disorders Institute, some autopsies have revealed that people with neurodegenerative diseases — such as Alzheimer’s disease , multiple sclerosis, and epilepsy — had problems with iron levels in the brain.
Iron overload conditions, such as primary hemochromatosis, require excess iron build-up levels within the body. The condition may cause serious complications without treatment, and may be life-threatening.
Canadian researchers concluded in 2007 that hemochromatosis is a “common and relatively straightforward genetic disease to treat.”
People can have a normal life expectancy with the treatment , particularly with early diagnosis and effective management.