what is this genetic disease?

First genetic disease in France, hemochromatosis affects 1 in 300 French people, or 200,000 patients. Hemochromatosis is usually relatively mild if recognized at age 20-30, but often serious and sometimes fatal if recognized at age 50-60. It is linked to a high ferritin level (protein that stores iron). In question, a genetic mutation hereditary. What are the symptoms ? How to establish the diagnostic ? What are the treatments ?

Definition: what is hemochromatosis?

Hemochromatosis East a genetic disease who trains an accumulation of iron in the body and certain organs in particular. The liver, pancreas, skin, heart are the main organs affected. Iron is used by the body according to its needs. In hemochromatosis, a genetic anomaly will generate a paradoxical message of lack of iron which will promote its digestive absorption. Since the body is not equipped to eliminate the iron that reaches it in excess, an overload then develops gradually.

What are the symptoms of hemochromatosis?

The patient usually presents no symptoms before young adulthood (“delayed genetic disease”), the accumulation of iron being very progressive (and the iron requirements important during childhood and adolescence). The clinical signs are varied and depend on the damage to the organs. May appear as follows:

• a chronic fatigue (which often makes you think of a lack of iron),
• of the joint pain (very evocative when they affect the second and third metacarpophalangeal joints, an attack which can be responsible for a “painful handshake”),
• a tanned tint to the skin,
• a hepatomegaly (increased liver volume) which may progress to cirrhosis,
• A diabetes,
• cardiac arrhythmias or even heart failure.

​​​​​​What causes hemochromatosis?

“For an individual to develop the disease, he must carry two copies of the defective gene (gene carrying the C282Y mutation). This subject is said homozygous : he therefore received one gene from his father and one from his mother; these two parents are said to be heterozygous (they can therefore pass on their gene but are not sick). It is therefore important to no longer speak of “heterozygous hemochromatosis“, describes Professor Pierre Brissot, hepatologist. Before adding: “Similarly, the situation called “composite heterozygosity”, which associates the classic mutation of hemochromatosis (C282Y) with another mutation (H63D), does not expose to the risk of hemochromatosis and is marked at most by an increase in iron levels in the blood without clinical consequences. A heterozygous subject composite should therefore not be diagnosed as hemochromatotic“.”They should no longer be called ‘secondary haemochromatosis’ but acquired iron overload. They may relate to multiple transfusions (red blood cells being very rich in iron) during hematological diseases which are responsible for chronic anemia, such as thalassemia in children or myelodysplasia (formerly called sideroblastic anemia) in adults“, explains Professor Brissot. They can also be due to a excessive intravenous iron supplementation. These acquired iron overloads can give rise to complications that are very similar to those of hemochromatosis, but the context in which they occur is therefore very specific and evocative. Iron excesses, usually very moderate, can be seen in other situations, such as:

Of the blood tests allow both to evoke the iron overload, to quantify it and to affirm the genetic nature of the disease.

► The increase in the transferrin saturation coefficient is the most suggestive sign of the diagnosis of hemochromatosis. It represents the iron load of transferrin, which is the iron transport shuttle in the bloodstream necessary to deliver iron to the various organs. An increase above 45% requires a new blood test: if it is still above 45%, the genetic test must be requested.

► Ferritin is a protein that stores iron in the cells. It is also a blood protein whose rate reflects, in hemochromatosis, the iron load of the body. However, it is essential to keep in mind thathyperferritinemia does not systematically reflect iron overload. Thus, by far the most common cause of hyperferritinemia is the metabolic syndrome (where the body’s iron load is either normal or only very moderately increased). In this case, transferrin saturation is normal. Inflammation or alcoholism can also cause hyperferritinemia out of iron overload.

► The search for the mutation C282Y is recommended, in a given subject, in the event of a verified elevation of transferrin saturation (the test is then reimbursed). It confirms hemochromatosis if the mutation is doubly present (C282Y/C282Y). During a family screening, the genetic test is the key examination, because it makes it possible to “classify” the members of the family into “normal” subjects (no C282Y mutation), heterozygous (1 mutation) or homozygous (2 mutations ). The genetic test is systematically reimbursed in this context of family investigation.

The treatment is based on the practice of bloodlettingwhich allow excess iron to be evacuated. Bloodletting consists of taking 400 to 500 ml of blood. They are initially performed weekly and then, once the iron overload has been eliminated, spaced out 2 to 4 months apart. This treatment is carried out for life. There are drugs capable of eliminating iron overload but they are only used exceptionally in hemochromatosis, as bleeding is usually effective and well tolerated. The treatment of the future will be supplement the body with hepcidin so as to correct the increase in iron absorption.

What diet when you have hemochromatosis?

“It is not not advised to follow an iron-free dietbut iron-rich foods should be moderated (such as red meat) and especially taking vitamin C tablets as it increases iron absorption“, advises Professor Brissot. Taking tea, provided that it corresponds to fairly large volumes, can be moderately beneficial (because tea decreases the absorption of iron).

Thanks to Pr Pierre Brissot, hepatologist, member of the Academy of Medicine and scientific adviser of theWestern Hemochromatosis Association (AH O).