Introduction Disease caused by excess iron deposition in nearly all tissues slow disease course with disease presenting in fifth decade (men) appears 10-20 years post-menopause in women see Treatment section May be primary or secondary primary mutation in HFE gene secondary (hemosiderosis) accumulation of iron secondary to frequent blood transfusions seen in RBC disorders (e.g. sickle cell) alcoholism high iron content in alcohol drinking water sourced from iron pipes Iron is not directly toxic to tissues iron generates free radicals that causes damage AR inheritance men > women Northern Europeans Presentation Symptoms cirrhosis malabsorption secondary to destruction of exocrine pancrease amenorrhea/↓ libido secondary to hypogonadism impotence fatigue arthritis/arthralgias (from iron/hemosiderin deposition) chondrocalcinosis Physical exam restrictive cardiomyopathy diabetes mellitus secondary to destruction of endocrine pancrease skin hyperpigmentation "bronze diabetes" Evaluation Labs ↑ ferritin (> 1000 ug/L) ↑ iron ↑ transferrin saturation (> 45%) ↓ TIBC secondary to ↓ transferrin synthesis ↓ LH/FSH Biopsy micronodular cirrhosis Treatment Medical repeated phlebotomy ↓ total iron stores menses serves this function in women with HFE mutation reason why disease appears post-menopause deferoxamine iron chelating agent Prognosis, Prevention, and Complications Untreated results in CHF ↑ risk of hepatocellular carcinoma