Haemochromatosis Haemochromatosis

I. Disease
Hereditary haemochromatosis is a genetic disease that causes the body to absorb and store too much iron, due to an iron intestinal hyperabsorption and leads to high morbidity and mortality if untreated. Haemochromatosis is preventable if diagnosed early. DNA testing is a valuable aid for early detection of this disorder, detecting over 85% of cases.

II. Epidemiology
Hereditary Hemochromatosis (HH) is regarded as one of the most common genetic disorder in Caucasians, particularly with Celtic origin (Bretons, Irish, English) with an estimated prevalence of 1/200 (or 1/350) (homozygotes – people with 2 copies of the mutation) and a carrier frequency (heterozygotes, people with one copy of the mutation) of 1/8. The sex ratio M:F is around 3:1, women being protected by physiological flow which makes them lose iron (pregnancy, menstrual flow)

III. Clinical signs
Commonly, the first symptoms are only biological and appear around 20 years.Clinical expression arises afterwards, around 40 year on men, and a little bit later on women.However, many people have no symptoms when they are diagnosed.And symptoms are no specific, which makes it a disease difficult to be diagnosed. Joint pain is the most common complaint of people with haemochromatosis. Other common symptoms include: fatigue, lack of energy, abdominal pain, loss of sex drive Impotence, heart problems. If the disease is not detected early and treated, iron may accumulate in body tissues and may eventually lead to serious problems such as : arthritis, liver disease, including an enlarged liver, cirrhosis, cancer, and liver failure, damage to the pancreas, possibly causing diabetes, heart abnormalities, such as irregular heart rhythms or congestive heart failure, impotence, early menopause,  abnormal pigmentation of the skin, making it look gray or bronze, thyroid deficiency, damage to the adrenal gland.

IV. Genetics
Haemochromatosis is an autosomal recessive inherited disorder. The gene responsible is HFE located in chromosome 6.Two main mutations in this gene principales are responsable of the disease :  C282Y and H63D.

1) The major mutation, Cys282Tyr (also known as 845A) is present in the homozygous state in 85% of Caucasians with clinically diagnosed haemochromatosis. Most homozygotes (with two copies of the mutation) and some heterozygotes (with one copy of the mutation) develop iron overload and haemochromatosis.

2) A second mutation, His63Asp (also known as 187G), appears to somewhat increase risk of iron overload. Although only a small percent of individuals (up to 6%) with this mutation develop haemochromatosis, DNA testing for haemochromatosis provides for effective early diagnosis and prevention. Results include genetic consultation for physicians, patients, and families with board certified genetic counsellors.

V. Genetic analysis – Technique
Biological sample: saliva on FTA cardAnalysis of the following mutations: Gene HFE (mutations H63D and C282Y)Analysis description: Real Time PCR (Taqman) allelic discrimination

VI. Treatment
The treatment to haemochromatosis is based in the elimination of the iron overload by bleedings. These simple bleeding allows a normal life quality and a normal life expectancy, when they start being done before apparition of clinical signs. It is therefore important to perform an early detection genetic testing, when a family member is affected.