History and Physical Examination
Patients with hereditary hemochromatosis may be asymptomatic or may present with general and organ-related signs and symptoms.
Symptoms from hemochromatosis usually begin between age 30 years and age 50 years, but they may occur much earlier in life. Most patients are asymptomatic (75%) and are diagnosed when elevated serum iron levels are noted on a routine chemistry screening panel or when screening is performed because a relative is diagnosed with hemochromatosis.
Early symptoms include severe fatigue (74%), impotence (45%), and arthralgia (44%); fatigue and arthralgia are the most common symptoms prompting a visit to a physician. The most common signs at the time of presentation are hepatomegaly (13%), skin pigmentation, and arthritis.
Clinical manifestations include the following:
• Liver disease (hepatomegaly, 13%; cirrhosis, 13%, usually late in the disease)
• Skin bronzing or hyperpigmentation (70%)
• Diabetes mellitus (48%)
• Amenorrhea, impotence, hypogonadism
Liver function abnormalities occur in 35-75% of patients. Among organ-related symptoms, hepatomegaly is seen in more than 95% of patients and can be accompanied by signs of chronic liver disease, such as abdominal pain and cutaneous stigmata of liver disease (palmar erythema, spider angioma, or jaundice), and liver failure (ascites or encephalopathy). Right upper quadrant tenderness with hepatomegaly or splenomegaly may be present.
Cirrhosis is due to progressive iron deposition in the liver parenchyma, and it is one of the most common disease manifestations of the tissue damage caused by hemochromatosis. Cirrhosis may be complicated by liver cancer years later (risk >200-fold). This condition is also the most common cause of death in patients with hereditary hemochromatosis.
Cirrhosis reversibility after iron removal has been reported, usually early in the course of liver disease, although reversal of advanced liver disease with varices has also been reported.