Between 60 percent and 90 percent of individuals with
hereditary hemochromatosis have the C282Y mutation
in both copies of the hemachromatosis (HFE) gene. This
mutation is more severe than H63D and almost always
results in symptoms and later health complications if
not treated. Many individuals will have increased serum-ferritin
levels but will not show symptoms for many years. Many
factors, including gender and diet, determine how old
a person may be when they first experience symptoms.
(This mutation is sometimes called 845 G to A.)
Approximately three percent of people with hereditary
hemochromatosis have one copy of the HFE gene with the
C282Y mutation and the other copy with the H63D mutation.
It is estimated that 0.5 percent to 2 percent of people
with this combination of mutations will develop symptoms
Approximately one percent of people have a change called
H63D in both copies of their HFE gene. These people
typically have a very mild course of disease resulting
from less iron accumulation. In fact, most individuals
with the H63D mutation in both copies of their HFE gene
never develop symptoms. (This mutation is sometimes
called 187 C to G.)
A small percentage of individuals who carry a C282Y
mutation in one copy of their HFE gene and have one
normal HFE gene may have mildly increased iron levels
and a 1.5-fold to 2-fold increased risk for cardiovascular
disease. However, the overwhelming majority of people
with this genetic test result are healthy carriers
of a mutation in just one HFE gene, and have normal
iron levels. About one in ten Caucasians in the USA
will have this test result.
Approximately six percent of individual patients have
mutations that are not commonly tested for or have not
yet been discovered. Other mutations may be included
in future genetic testing for hereditary hemochromatosis.
The numbers of individuals with these mutations are
very small so researchers do not yet fully understand
the clinical implications of these changes in the HFE
gene. They may have unknown mutations in their HFE genes,
or iron overload caused by mutations in a completely
different, as yet unknown gene.