Hereditary Hemochromatosis: The HFE Gene Test That Explains High Ferritin

If your ferritin came back high, the HFE gene test is what tells you whether the cause is inherited. Hereditary hemochromatosis makes the body absorb more iron from food than it needs, year after year, until the surplus is stored in the liver, heart, pancreas and joints. It is the most common inherited condition among people of Northern European descent, and one of the few that is genuinely simple to treat — provided it is found before the iron does damage.

AvoVita offers the Hereditary Hemochromatosis, HFE Variant Analysis through Mayo Clinic Laboratories for $1,600. No physician requisition is required, and the blood is drawn at your home or office anywhere in Calgary and the surrounding towns.

What does the HFE gene test actually look for?

Three specific variants in the HFE gene: C282Y, H63D and S65C. Mayo Clinic Laboratories analyses them by droplet digital PCR (ddPCR) on a whole blood sample, and reports which copies of each you carry. S65C is reported only when it is found alongside C282Y, because on its own it carries no established clinical weight.

Two copies of C282Y — one inherited from each parent — account for the large majority of clinically significant HFE-related iron overload. Roughly one in ten people of Northern European ancestry carries a single copy, and somewhere between one in 200 and one in 300 carries two.

How the results read

• Two copies of C282Y (homozygous). The genotype most strongly associated with iron overload. It is a risk finding, not a diagnosis — iron studies and clinical assessment decide whether overload is actually present.
• One C282Y and one H63D (compound heterozygous). A modest increase in risk. Most people with this combination never develop clinically significant overload, and when they do it tends to be mild.
• One copy of H63D, or one copy of C282Y, alone. Carrier status. Mayo's own report language is that a single H63D variant "is unlikely to be of clinical significance in the absence of other disease-causing variants."
• No variants detected. Reduces the likelihood of HFE-related hemochromatosis but does not rule out iron overload from other causes.

You can see exactly what the report looks like before you order: Mayo Clinic Laboratories publishes a sample HFE variant analysis report showing the result, the interpretation paragraph and the method notes.

Who should consider the HFE test?

• Anyone whose ferritin or transferrin saturation came back above range on a previous blood test, particularly if it has stayed high on a repeat.
• Anyone with a parent, sibling or child diagnosed with hemochromatosis. Siblings of someone with two C282Y copies have roughly a one in four chance of the same genotype.
• People with unexplained fatigue alongside joint pain, classically in the knuckles of the index and middle fingers.
• People with unexplained liver enzyme elevation, diabetes appearing without the usual risk factors, or a cardiomyopathy with no obvious cause.
• People of Northern European descent who simply want to know their genotype before anything goes wrong.

Should I check my iron levels first?

Usually, yes — and it is much cheaper. Iron studies tell you whether you are carrying too much iron right now. The HFE test tells you whether your genes explain it. Most people are better served by the first question before paying for the second.

Two tests answer it. Ferritin ($110) measures your iron stores. Iron + Total Iron Binding Capacity ($125) gives you transferrin saturation, which rises earlier in iron overload than ferritin does and is the more specific of the two.

If both come back normal, hereditary hemochromatosis is unlikely and genetic testing is rarely the right next spend. If ferritin is elevated and transferrin saturation is high — above roughly 45 per cent — HFE genotyping is the logical next step, and that is the point at which $1,600 buys you a real answer rather than a curiosity.

Ordering both iron tests in the same appointment costs one $85 in-home collection fee, not two. The collection fee is charged once per appointment however many tests you order.

What the test cannot tell you

Genotype is not diagnosis, and this is where a lot of genetic testing gets oversold. Many people who carry two copies of C282Y never accumulate enough iron to cause harm — the condition has incomplete penetrance, and diet, blood loss, alcohol and other genes all move the outcome. A negative result does not exclude hereditary hemochromatosis caused by variants in HFE that this test does not cover, or by entirely different genes, and it does not exclude iron overload from repeated transfusions, liver disease or other secondary causes.

Two further limits worth knowing. This is a laboratory-developed test: Mayo Clinic Laboratories validated it and the U.S. FDA has not cleared or approved it, which is standard for tests of this kind. And if you have had an allogeneic bone marrow transplant, the result will reflect your donor's genotype, not your own.

Mayo's own report recommends that genetic consultation may be of benefit. We agree — a result of this kind is worth reviewing with a physician or a genetic counsellor, both for what it means for you and for what it means for your siblings and children.

Why finding it early is the whole point

The treatment for iron overload is therapeutic phlebotomy — taking off a unit of blood on a schedule until iron stores come down, then maintaining. It is cheap, it is low-tech, and it works. Caught before cirrhosis or diabetes has set in, life expectancy is normal. Caught after, the organ damage does not reverse. That gap is the reason the test exists.

How testing works with AvoVita

You do not need a physician requisition. You order the test yourself through the AvoVita portal, and a FloLabs phlebotomist comes to your home, your office, or wherever suits you — anywhere in Calgary, Airdrie, Cochrane, Okotoks or Chestermere. There is no clinic to sit in and no waiting room.

One scheduling note: this test ships on Tuesdays. Whole blood for HFE analysis goes to Mayo Clinic Laboratories on the weekly Tuesday shipment, so your collection is booked for a Tuesday rather than any day of the week. Your report is available 7 to 9 days after shipping and is delivered to your private AvoVita client portal, where you can download it and take it to whichever provider you choose.

AvoVita arranges testing and delivers results. We do not diagnose, treat or prescribe, and we recommend reviewing any result with a healthcare provider of your choice.