Haemochromatosis type 3

Haemochromatosis type 3 is an inherited iron overload disorder linked to deficiency of transferrin receptor 2, encoded by the TFR2 gene. It follows an autosomal recessive pattern, appearing when both copies of TFR2 are altered, or when one TFR2 change is paired with one in the HFE gene. Penetrance is reduced, so some people with pathogenic variants never develop symptoms, and up to three quarters of those who inherit it may be asymptomatic. When symptoms occur they include severe fatigue, impotence, joint pain, an enlarged liver, skin pigmentation and arthritis, and the wider effects reach the skeletal, endocrine, cardiovascular, neurological, genitourinary and skin systems. Untreated iron overload can progress to liver cirrhosis, diabetes and bronze-colored skin. It is one of four types of hereditary haemochromatosis, which are classified by age of onset, genetic cause and mode of inheritance.