H E M A T O L O G Y

C L I N I C

Hereditary hemochromatosis Introduction Hereditary hemochromatosis (HH) is an iron overload disease of genetic origin. Its usual form, named HFE-related hemochromatosis (or Type 1 hemochromatosis), affects only white populations where it is one of the most frequent genetic diseases. Other genetic forms of hemochromatosis are rare but present worldwide; they correspond to non-HFE mutations and are named Type 2, 3, or 4 hemochromatosis.

Cause • Most forms of HH (Types 1, 2, and 3) are due to the decreased production by the liver of the iron hormone hepcidin, leading to an increased absorption of dietary iron. Therefore, iron concentration in the blood increases. • One rare form of hemochromatosis (Type 4 hemochromatosis) is due to decreased ferroportin activity. Ferroportin is the protein permitting the iron exit from the cell into the blood. Therefore, iron excess develops within the organs due to decreased iron exit (and not to increased iron entry). Blood iron concentration, in this hemochromatosis form, is diminished, contrasting with elevated body iron stores. Importantly, due to the absence of non-transferrin bound iron, organ damage is less pronounced than in Type 1 hemochromatosis.

Symptoms and signs 1. For the usual form of hemochromatosis (HFErelated or Type 1 hemochromatosis). 2. a long latent phase, the symptoms appear around 30–40 years of age in men, and 40–50 years in women. The main signs include chronic fatigue (physical, psychological, and sexual, e.g. impotence in men). Joint pains that correspond to inflammatory rheumatism and are often misdiagnosed. One suggestive location concerns the hands (Fig. 1). Osteoporosis may be responsible for backache and vertebral fractures. Skin is abnormally bronzed. Liver symptoms include enlargement, a moderate and chronic increase of serum transaminases, development of hepatic fibrosis with cirrhosis and

370

© W. S. Maney & Son Ltd 2013 DOI 10.1179/1024533213Z.000000000222

even hepatic cancer. Diabetes is related to pancreatic iron excess. Cardiac iron overload can be responsible for rhythm disturbances (palpitations) and cardiac failure. 3. For the non-HFE related forms. The symptoms of Type 2 and Type 3 hemochromatosis resemble Type 1 but Type 2 affects solely younger people (‘juvenile hemochromatosis’) – with predominant cardiac and endocrine symptoms – whereas type 3 can affect both adult and young patients. Type 4 HH (‘ferroportin disease’) is often clinically asymptomatic.

Tests 1. For the usual form of hemochromatosis (HFErelated or type 1 HH) Blood iron concentration is increased (above 25 μmol/l), together with an increased transferrin saturation: over 60% in men and 50% in men, often reaching 100% (normally

Hereditary hemochromatosis.

Hereditary hemochromatosis. - PDF Download Free
76KB Sizes 0 Downloads 0 Views