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Hemochromatosis type 3
Type 3 hemochromatosis is a form of rare hereditary hemochromatosis (HH) (see this term), a group of diseases characterized by excessive tissue iron deposition of genetic origin.
Less than 50 cases have been reported in the literature. It is mainly found in Caucasian populations but has also been reported in Asia.
Type 3 hemochromatosis concerns middle aged-adults but also adolescents and young adults (<30 years old). It resembles type 1 (HFE-related) hemochromatosis (see this term) and presents with liver disease, hypogonadism, arthritis, diabetes and skin pigmentation.
It is due to mutations of the transferrin receptor 2 gene (TFR2) on chromosome 7. These mutations lead to hypohepcidinemia which in turns causes iron excess through increased intestinal iron absorption and iron release from the spleen.
Diagnosis is based on biochemical testing using serum transferrin saturation and serum ferritin, and on imaging testing for diagnosing visceral iron overload (magnetic resonance imaging). Molecular genetic blood testing permits to establish the diagnosis in a non invasive way (i.e. without a liver biopsy).
Differential diagnosis includes: i) for hyperferritinemia: alcoholism, polymetabolic syndrome, inflammatory conditions; ii) for visceral iron overload: a) in younger patients: type 2 hemochromatosis (see this term) and post-transfusional iron overload in the case of hematological diseases such as thalassemia major, sickle cell disease, and rare anemias (see these terms) b) in older patients: Type 1 hemochromatosis and post-transfusional iron overload (especially myelodysplastic syndromes).
Transmission is autosomal recessive. Genetic counseling must be proposed to affected families, informing them of the risk of inheriting the disease-causing mutation.
Management and treatment
Patients are treated by repeated phlebotomies that are performed weekly until the ferritin level reaches 50 µg/l, after which they are performed every 1-3 months.
Prognosis can be considered as good, provided that the patients are treated early, before the development of severe visceral complications (especially cirrhosis).