Hereditary hemochromatosis usually develops silently, and when symptoms do appear they come from iron deposited in a few characteristic organs.
How it presents
Most patients with HFE-related HH come to medical attention in the asymptomatic phase of the disease, for example when relatives of a symptomatic homozygous patient are tested as part of family screening.
The most common clinical presentations of patients with HFE-related HH are:
- weakness and lethargy
- abdominal pain, mostly vague pain in the right upper quadrant
- arthralgia
The joint pain of hemochromatosis has a characteristic distribution: it typically affects the second and third metacarpophalangeal joints, and calcium pyrophosphate crystals can be deposited in the cartilage (chondrocalcinosis).
Loss of libido and potency in men has two mechanisms: testicular failure from iron overload of the gland, and a lack of gonadotropin from iron damage to the pituitary gland. Hypothyroidism from iron overload of the pituitary has also been reported, similar to the gonadotropin effect.
Liver-related manifestations include hepatomegaly, and less commonly ascites, edema, jaundice and splenomegaly.
Age, sex and penetrance
Most patients who are symptomatic are diagnosed between 40 and 50 years of age, and homozygosity for the C282Y mutation is found equally in men and women. Clinical penetrance, however, is lower in women than in men, because blood loss during childbirth and the menstrual cycle removes iron. Before screening was widespread, women presented about ten years later than men and were greatly outnumbered among symptomatic cases; with screening the two sexes are identified at similar rates, but the proportion of C282Y homozygous women who develop definite disease remains much lower than in men.
Complications
During the past years, thanks to the screening tests and the earlier diagnosis of HFE-related HH, the total incidence of the end-stage complications has fallen dramatically and many are now prevented. These complications, which were very frequent in the past, are:
- diabetes mellitus
- cirrhosis
- skin hyperpigmentation
- hepatomegaly
- heart failure