Genetics
Recessive Gene Disorder.
Haemochromatosis is a recessive gene disorder which means for the condition to be passed on, both mother and father must be carriers of the gene. If a person inherits only one mutated haemochromatosis (HFE) gene, they are known as carriers. Around one in seven people carry the mutated HFE gene.
Carriers won't develop the condition themselves, but may pass the mutation on to their children.
If two carriers conceive, their child has a 50 per cent chance of inheriting one mutated HFE gene and becoming a carrier and a one in four chance of inheriting both mutated HFE genes and therefore being at risk of excess iron absorption and developing symptoms of haemochromatosis.
Of those with haemochromatosis, 1 in 700 will have no mutation in the HFE gene and this is known as Non-HFE haemochromatosis and is due to mutations in other genes.
Since the identification of the gene which causes haemochromatosis was made in
1996, a simple genetic test has been developed to test suspected sufferers as
well as their close blood relatives. This test is available in all states of
Australia. Further genetic information is available from the group for members
and other interested parties.
Gene testing.
With the HFE gene test more and more families are being tested. This brings to light the increasing number of relatives and children with
one or both mutations in the haemochromatosis gene mutation.
There are two mutations in the haemochromatosis (HFE) gene.
The C282Y mutation is associated with most cases of hereditary haemochromatosis.
The second mutation, H63D is much less significant.
Positive HFE no symptoms
When 2 C282Y (homozygous) or one C282Y (heterozygote) plus one
H63D (compound heterozygous) genes are present with normal serum
ferritin and transferrin saturation this means that there will
be no symptoms of the disorder (iron-overload).
Currently hereditary haemochromatosis (iron-overload) involves C282Y homozygotes
and compound heterozygotes.
Compound heterozygotes usually have a milder form of haemochromatosis.
Positive HFE with iron-overload.
May or may not be symptomatic
Homozygote for C282Y and or compound heterozygote C282Y + H63D
Elevated SF and elevated TS
What does this mean?
- Your children or relative may have the normal HFE gene.
Negative HFE — no need to test further but remember there are other causes of iron overload with a negative HFE gene test.
Remember that tests can be faulty.
If there is any prolonged symptoms of fatigue, and/or endocrine problems then iron studies are necessary and may be repeated.
- Your children or relative may have one C282Y gene and one H63D gene.
- Your child or relative may have 2 C282Y genes.
Positive 2 C282Y ( HFE) genes.a) Iron studies are performed and if transerrin saturation % is elevated look at serum ferritin.
If ferritin is elevated then iron-overload is occurring and treatment is required. Iron levels (SF & TS) should be normalised.
b) If the serum ferritin remains normal, then repeat tests every 1-2 years
c) Rare cases are being reported in instances where the father has haemochromatosis the mother negative and child has 2 HFE genes.
Positive C282Y + H63D. (compound heterozygote)
The H63D is the second
mutation and combined with C282Y may accumulate iron. Do iron studies,
serum ferritin and transferrin saturation.
If transferrin elevated,
then watch for elevation of serum ferritin.
Iron overload does not occur until serum ferritin is above normal limits.
There is a distinct possibility of a spontaneous mutation.
More mystery!!!!, we have to wait for further answers in this area.