Clinical manifestations and cofactors influencing the penetrance of HFE-hemochromatosis. Most patients are now diagnosed in the early phase before the development of organ damage-related symptoms. Heart and endocrine manifestations are often the presenting symptoms in severe (juvenile) non-HFE hemochromatosis forms. They can also be seen in patients with severe HFE- hemochromatosis and substantial cofactors burden,³⁴ but they are now exceedingly rare. HCV, hepatitis C virus; QoL, quality of life.