What is Hemochromatosis?

Hemochromatosis is a hereditary disease (autosomal recessive inheritance) due to a mutation in the gene responsible for manufacturing the protein that controls iron absorption. As a consequence of this mutation, the iron provided by the diet is absorbed in an uncontrolled way, which gives rise to an excess of iron in our body. Excess iron causes damage to the joints, heart, liver, and pancreas.

It is a much more common disease in men (women are partially protected by blood loss during menstruation), which usually produces the first symptoms between 40 and 60 years of age. There are juvenile forms of the disease, much rarer, due to mutations in genes that make other proteins related to iron metabolism.

What are the causes of hemochromatosis?

Hemochromatosis is a genetic disease that affects a protein that is responsible for controlling the intestinal absorption of the amount of iron necessary for the body. The alteration of said protein makes the intestine not know when to interrupt the absorption of iron from the diet and that it absorbs absolutely all the iron that reaches it. 

The accumulation of iron over the years is responsible for this disease. However, not all people with genetic defects develop the disease. Various factors, such as alcohol consumption, the presence of fatty liver, sex, and the amount of iron consumed in the diet, favor or protect the development of hemochromatosis in people with genetic alteration.

In addition to this hereditary alteration, there are some diseases of the red blood cells and the liver that can also cause an overload of iron in our body.

Finally, receiving an excessive number of blood transfusions can increase the body’s iron.

What symptoms does the disease produce?

In the initial phases of hemochromatosis, the symptoms are nonspecific, such as tiredness, joint pain (arthralgia), changes in skin color, decreased sexual desire, and elevated glucose. In advanced stages, clinical data indicate the involvement of different organs due to iron deposits:

Skin. It acquires a dark coloration (like bronze), hair may be lost and small spider veins may appear.

Liver. It produces chronic liver disease that can lead to cirrhosis. The liver is enlarged in most patients. In advanced situations of cirrhosis, the appearance of liver cancer is frequent, in fact, liver cancer is the leading cause of death in patients with hemochromatosis who receive treatment.

Pancreas. It leads to pancreatic insufficiency that results in diabetes, present in 2/3 of patients.

Heart. It produces cardiomyopathy, which can lead to the development of heart failure. Cardiac arrhythmias are also common.

Joints. It produces joint damage that usually affects the hands and becomes asymmetrical involvement of multiple joints, especially fingers, hands, wrists, ankles, knees, and hips. It is frequently associated with chondrocalcinosis.

Decreased activity of sex hormones (hypogonadism) as a result of iron deposition in the pituitary gland, an area of ​​the brain that secretes hormones that stimulate the sexual organs. It manifests as loss of sexual desire, impotence, the disappearance of menses, growth of the breasts in men (gynecomastia), and atrophy of the testicles.

How is hemochromatosis diagnosed?

It should be investigated if there is a suggestive history of hemochromatosis in the family, that is if there are other relatives with liver or heart disease or diabetes. This finding and clinical suspicion guide the diagnosis.

To make a definitive diagnosis, a blood test is required. in which it is observed that the body’s iron stores are saturated. Patients have an elevated blood iron concentration, ferritin (the protein that measures the body’s iron stores) concentration usually greater than 1000 mcg/L, and a transferrin saturation index greater than 50%. 

There are some diseases that also produce elevations in ferritin levels (generally less than 500 mcg/L), so not everyone with high ferritin has hemochromatosis.

The diagnosis must be completed with the search for the genetic alteration. There are 2 well-recognized mutations that are associated with the development of hemochromatosis, C282Y, and H63D. 

It is necessary to be homozygous (that is, to have both genes affected, the one from the father and the one from the mother) to have the disease, although many homozygotes for the H63D mutation never develop the disease or have signs of iron overload. 

Some homozygotes for the C282Y gene may have iron overload without clinical evidence of the disease. Some people who have a single allele of the affected C282Y gene and another of the affected H63D gene may also develop the disease, generally, if they are also heavy alcohol drinkers or have fatty liver.

Performing an MRI of the liver can also estimate the iron overload of this organ. Finally, in some circumstances, it may be necessary to perform a biopsy of an organ(usually a liver biopsy) where it is observed that the iron deposits are greatly increased.

What is the prognosis for those affected?

Many people with hemochromatosis never have clinical manifestations of the disease. Other people, however, do have symptoms and progressive deterioration of their organs. If hemochromatosis is diagnosed early and treated, life expectancy is usually normal or near normal. 

In advanced stages, in which there is already damage to some organs, treatment can improve the disease or slow down its progression. However, if there is cirrhosis, it is irreversible. Patients often die from complications of cirrhosis, liver cancer, or heart failure.

Is hemochromatosis hereditary?

In Europe 1 in 10 people is a carrier of the affected gene. In addition to the genetic alteration, the development of the disease depends on other factors, such as alcohol consumption, blood loss in women during menstruation, and the amount of iron that is ingested with the diet; also, and to a lesser extent, whether the patient has donated blood frequently.

A genetic study should be carried out on siblings and children(over 18 years of age) of patients with hemochromatosis or with genetic alterations (homozygous C282Y). 

This is important to detect the disease early and start treatment. Couples of people with a C282Y allele can also be asked to see if the couple also has an altered allele and thus know the risk that their children may be born with a higher risk of suffering from the disease.