Hereditary Hemochromatosis

Hereditary Hemochromatosis (HH) is the most common genetic disorder of persons of northern European extraction.  Approximately 1 in 200 to 300 persons of northern European extraction has the disorder.  Hemochromatosis has been

found in virtually all populations.  There are different forms of the disorder but here we will consider northern Europeans.  

The incidence of HH in persons of Irish extraction is higher than the average rate for northern Europeans.  A rate exceeding 1 in 100 has been found in  Ireland.  Most cases of HH occur in patients who have two copies of the mutation known as C282Y which is found on the HFE gene.  A smaller percentage of patients may carry one copy of C282Y and one copy of another mutation known as H63D.  These patients are known as compound heterozygotes.  Other less common combinations occur such as C282Y heterozygotes where the patient only has one copy of C282Y but has hemochromatosis.  In these cases another gene or genes is present.  Sometimes this gene or genes can be identified.  Identification of such genes is currently the source of much research into hemochromatosis.

HH is characterized by excessive absorption of dietary iron and a consequent progressive increase in total body iron stores.  Of interest it is non-heme iron or the iron contained in sources such as vegetables which is excessively absorbed in HH.  Iron accumulates in the parenchymal cells of the liver, the heart, pancreas, anterior pituitary and skin.  This accumulation of iron in body tissues causes disease. The body needs iron to function and has an ability to store large amounts especially in the liver.  However when this storage capacity is exceeded disease occurs.

In severe HH the disorder manifests as potentially life threatening conditions such as septicemia, cirrhosis of the liver, liver cancer, diabetes, heart failure and heart arrhythmias.  Arthritis is common and a severe arthritis involving numerous joints may occur.  Ovarian and testicular failure secondary to iron deposition in the anterior pituitary and possibly the hypothalamus may occur.  Rarely hypothyroidism may occur.

If HH is not treated liver disease may be fatal.  The morbidity and mortality of HH can be reduced by early diagnosis and treatment by phlebotomy or blood letting.  If a patient with HH is treated before cirrhosis of the liver develops liver functioning can be improved and fibrosis of the liver may be reversed.

There is frequently a delay between the onset of symptoms and diagnosis.  This is because early symptoms such as fatigue and arthralgia are nonspecific.  A high degree of suspicion is needed to make the diagnosis of HH in a patient if the initial symptoms are vague.  Because of the inherited nature of hemochromatosis relatives of those with HH are at increased risk.  Here it is easier to make the diagnosis because an initial case has been identified.

It is very important to make an early diagnosis of Hereditary Hemochromatosis  because patients who have not developed cirrhosis and are treated by phlebotomy have a normal life expectancy.  Treatment is life long.