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Less than 100 reported cases were reported with a broad geographical distribution. Both sexes are equally affected.

Age of onset is usually less than 30 years. This juvenile form of hemochromatosis has the classical features of symptomatic HC but is also characterized by severe cardiomyopathy and hypogonadism. Arthropathy, hepatic fibrosis, glucose intolerance, and increased skin pigmentation are frequent. Biochemical abnormalities include elevated serum iron, transferrin saturation and ferritin.

Two types of the disease have been described, both being transmitted in an autosomal recessive way. The most frequent form is caused by mutations in the hemojuvelin (HJV) gene on chromosome 1 and the second form is caused by mutations in the hepcidin (HAMP) gene on chromosome 19. These mutations result in complete or major hepcidin deficiency, thus increasing drastically duodenal iron absorption and iron release from the spleen.

Diagnosis is based on biochemical testing for serum transferrin saturation (>90%), serum ferritin concentration (often >2000 microg/L), and on magnetic resonance imaging (MRI) for quantifying visceral (especially hepatic and cardiac) iron overload. Molecular genetic blood testing allows, in most cases, to confirm the diagnosis.

Differential diagnosis includes TFR2-related hemochromatosis and post-transfusional iron overload in the case of hematological diseases such as thalassemia major, sickle cell disease, and other rare anemias.

Genetic counseling should be offered to first-degree relatives of patients with genetically confirmed HJV or HAMP-related hemochromatosis. Particular focus should be given to siblings as they are at the highest risk (25%).

Intensive phlebotomies, sometimes combined with iron chelation therapy, form the basis of treatment.

Complications like heart failure are often fatal. Early and intensive iron depletive therapy can significantly improve an otherwise devastating prognosis.