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Hemochromatosis

Clinical aspects

Classic Hemochromatosis or Type 1 is a disease characterized by excessive intestinal
Iron absorption which it accumulates initially in hepatic liver and later in other organs.

ciclo ferro x sito
Fig.1 - Iron cycle

The iron (Fig.1) food is absorbed in the intestine, mainly in the duodenum, and it passes into the bloodstream where it binds to transferrin (Tf) protein to carry it to the liver or to laydown as ferritin or to organs that use it (muscles, bone marrow, …). The bone marrow produces red blood cells (RBCs) iron taking over, essential for the oxygen transfer; aged red blood cells are destroied in the spleen and the iron release comes back into the bloodstream to reemploye it.
The iron excess causes a liver damage (liver cirrhosis, sometimes complicated by hepatocarcinoma), cardiopathies, diabetes mellitus, arthropathies, osteoporosis, hypogonadotropic hypogonadism, chronic fatigue, skin hyperpigmentation. The biochemical abnormalities include increased of the serum iron, of the transferrin saturation coefficient and of the serum ferritin levels. The disease onset varies from 30 to 50 years and the clinical evidences are more frequent in males, because in the women the iron excess is eliminated through menstruation flux or pregnancy.
The classical hemochromatosis is described exclusively in Caucasian populations with a frequency of 1 in 300 in Northern Europe and about 1 in 1.000 in Italy.

Genetic aspects

Type 1 Hemochromatosis is a monogenic disease with a recessive autosomal trasmission caused by mutations, DNA alterations of the HFE gene, localized on chromosome 6. The HFE gene encodes for a protein, the iron “sensor"; in normal conditions this protein is localized on the intestinal cell surface and like a sensor, it control the iron absorption. The most frequent mutation of the HFE gene, known as C282Y, causes a modified protein not expressed on the intestinal cells surface so in the "sensor" absence the intestinal cells absorb a greater amount of iron.
Another mutation (H63D) allows the expression protein on the intestinal cells surface but it is unable to perform its sensor function, so leading an iron overload. In the general population the 60-90% of patients (64% in Italy with gradient decreasing from North to South) with classical hemochromatosis is homozygous for the C282Y mutation, 5% C282Y / H63D compound heterozygous with less severe clinical events and 1 -2% H63D homozygous which develop the iron overload only in association with other risk factors. Recently it was identified another mutation (S65C) and if it is inherited with the C282Y or H63D, it seems associated with a moderate iron accumulation and so an increased risk of a mild form of hemochromatosis development.

Genetic test

In Tecnobios Prenatale Eurogenlab is available a genetic test for the three main mutations identification of the HFE gene, C282Y, H63D, and S65C; This test also allows to identify the HFE genotype to define for eachone if the patient is normal or mutated homozygous, heterozygous (healthy carrier), compound heterozygous.

Genetic counseling

Tecnobios Prenatale Eurogenlab also provides for a genetic counseling service to inform patients and their families, about of family transmission risk, the diagnosis and treatment likelihood.

Response times

The analysis result is available within 10 working days from draw blood.

Material analyzed

The DNA is extracted from peripheral blood lymphocytes collected in EDTA tubes.

References
Malattie genetiche – Cao, Dalla Piccola, Notarangelo – Piccin (2004)
www.orpha.net
www.emocromatosi.it