Juvenile Hemochromatosis – What is it?

Juvenile hemochromatosis or Hemochromatosis type 2  is different from the more common hemochromatosis type 1 or HFE related hemochromatosis primarily in that it is a more severe disease. Hemochromatosis type 2 affects both sexes equally

While hemochromatosis type 1 has a male predilection, Juvenile hemochromatosis also has faster iron deposition in parenchymal cells of the body and causes clinical symptoms much earlier in life. It does not take the many decades to manifest as does the usual HFE related hemochromatosis. Sufferers are usually severely affected by the second and third decades of life. Juvenile hemochromatosis is associated with a more frequent occurrence of hypogonadism and cardiomyopathies. Premature menopause or heart failure may be presenting symptoms. Although liver dysfunction is part of the syndrome it is not as prevalent as in HFE related hemochromatosis. If the patient with juvenile hemochromatosis is not treated he or she may succumb to heart failure before the age of 30 years. It is not uncommon for a patient with juvenile hemochromatosis to have had hundreds of phlebotomies. Ferritin levels measured in the thousands are frequent occurrences. Juvenile hemochromatosis is very difficult to control because of the repeated need for venesections. If a patient has cardiac complications frequent venesections may place further strain on a damaged heart.

Hemochromatosis type 2 is an autosomal recessive disorder, so two copies of abnormal genes are required for the disorder to occur.

Juvenile hemochromatosis is divided into two forms.

  1. Type 2A is due to a mutation of the protein hemojuvelin which is coded for by the HJV gene. Type 2A is the more usual form of juvenile hemochromatosis. The HJV gene is located on chromosome 1q21. The most common mutation is G320V but over 20 novel mutations have been identified.
  2. Type 2B is due to a mutation of the hepcidin protein which is coded for by the HAMP gene. The HAMP gene is located on chromosome 19q13. Type 2 hemochromatosis may result from homozygous or compound heterozygous mutations in the HJV or HAMP genes.

Recent work identified an Italian brother and sister pair where a form of hemochromatosis resembling juvenile hemochromatosis resulted from the synergistic effect of Q317X homozygous mutations in the TfR2 gene (the cause of hemochromatosis type 3) and HFE C282Y/H63D compound heterozygosity. Hemochromatosis types 1 and 3 are not as severe as type 2 however the combination of hemochromatosis types 1 and 3 has been shown to produce a clinical presentation similar to hemochromatosis type 2

Juvenile hemochromatosis occurs worldwide. In Canada a cluster of patients occurs in Quebec in Saguenay-Lac-Saint-Jean. There are reports from numerous other countries including Greece, USA, Italy, England, Albania, Australia, France, Germany, Slovakia, Croatia, Romania and China. The original identification of the HJV gene came from collaborative work involving Greek, French and Canadian patients.

A mutation in the HAMP gene can pair with a HFE mutation and give a digenic form of hemochromatosis. This combination of single hemochromatosis type 1 and hemochromatosis type 2 mutations is not as severe as juvenile hemochromatosis.