Heterozygous hemochromatosis: What to know

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Hereditary hemochromatosis (HH) is a genetic condition in which the body absorbs and accumulates too much iron.

Each person has two copies of every gene. People inherit one set from one parent and the other from the second parent. Each gene has its own functions, such as managing iron absorption.

Heterozygous HH means a person has one healthy gene for managing iron absorption, which they inherited from one parent, but the other copy from the other parent is the gene for HH.

Individuals in this category are carriers, meaning they have a copy of the gene that can pass to children, but they may or may not have any symptoms. Typically, the healthy gene for iron absorption is sufficient to manage this function without problems.

In contrast, those with homozygous HH have two copies of a gene that causes hemochromatosis, one from each parent. People in this category are highly likely to develop the condition, but not all of them will show signs and symptoms.

HH occurs due to a difference in a gene known as HFE. This gene regulates the synthesis (production) of the hormone hepcidin, which determines the amount of iron a person absorbs from their diet and how much iron their body releases from storage sites around the body.

Storage sites include the:

• liver
• skin
• pancreas
• heart
• joints
• pituitary gland

When a person develops hemochromatosis, it increases their iron absorption from food, even if their dietary intake is typical. Eventually, the storage of iron in cells leads to cell death and the formation of fibrous tissue that affects organ function.

There are several different types of HH gene a person can inherit, and they each affect iron absorption in different ways. The most common in the United States are C282Y and H63D, accounting for 90% of all cases. These genes are more common among people of Northern European descent.

While males and females are equally likely to have HH genes, males are more likely to manifest symptoms and complications. This may be because most females menstruate, meaning they lose iron through blood loss, delaying the onset of symptoms.

Not every person with HH has symptoms, particularly those with only one copy of the associated genes. People with heterozygous HH often have no symptoms or only develop mild symptoms.

In those who do develop symptoms, signs may not show until after 40 years old. On average, females typically develop symptoms 10 years later than males.

The symptoms of HH can include:

• tiredness or weakness
• erectile dysfunction or loss of interest in sex
• change of skin color, which may look metallic, gray, or bronze
• joint pain, especially in the hands and knees
• pain in the abdomen over the liver

Because people with heterozygous HH do not usually develop iron overload, they do not have as much risk of the potential complications of HH as others. However, they do have a higher likelihood of developing diabetes. Scientists are not sure why this is the case.

Diagnosing heterozygous HH requires genetic testing. This is because, unlike those with homozygous HH, people with only one copy of a hemochromatosis gene also will typically not have unusually high iron levels, so blood testing may not be helpful.

To begin the process, a doctor may ask about a person’s medical and family history, particularly about relatives who may have shown signs of HH. If they suspect HH, they refer a person for genetic testing, which may involve taking a blood sample or swabbing inside the cheek.

Alternatively, some companies offer genetic testing for HH via mail-order kits.

Heterozygous HH may not need treatment. However, if a person’s iron level is higher than typical, a doctor may suggest blood draws (phlebotomy).

Phlebotomy is the main treatment for HH. It involves drawing blood through a needle to reduce the iron level. The frequency of this treatment will depend on how much a person’s iron level needs to decrease. After the iron level returns to a typical range, doctors may periodically check it remains within this range.

People who cannot have phlebotomy or who are afraid of needles may benefit from chelation instead. This binds iron that the body then excretes via urine.

Below are answers to some frequently asked questions about HH.

How common is HH?

In the U.S., approximately one in 300 non-Hispanic white people have HH. The rates are lower in individuals of other ethnicities and races.

What is the difference between homozygous and heterozygous?

“Homozygous” refers to inheriting two copies of a gene, one from each parent. “Heterozygous” means inheriting one copy of a gene from only one parent.

What is the ferritin goal in HH?

Ferritin is a blood protein that contains iron. The goal of phlebotomy is to get a ferritin level of less than 50 micrograms per liter to maintain health.

Heterozygous hemochromatosis is when a person has one copy of a gene that causes the body to absorb too much iron.

However, an individual with heterozygous hemochromatosis will likely not experience iron overload, nor many symptoms, as they will have one hemochromatosis gene and one healthy gene. The healthy gene can often regulate iron effectively enough on its own.

Heterozygous hemochromatosis does not necessarily require any treatment. However, the gene can pass to children, which will mean they carry it as well. If the other parent also has a gene for HH, there is a higher likelihood that children will have symptoms.

People who suspect they may have genes for hemochromatosis may benefit from speaking with their doctor about genetic testing.