Header Information
Canada's most common genetic disorder — 1 in 9 are carriers
Header Information
Hemochromatosis —
1 Canadian in 9 is a carrier
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Glossary
Autosomal
Humans have 23 pairs of chromosomes. Chromosomes 1-22 have nothing to do with sexual characteristics and are called 'autosomal' chromosomes (or autosomes).
C282Y
Refers to the most common mutation of the HFE gene. The C282Y mutation results in a change in the amino acid in the protein produced, and affects how the protein 'folds,' thereby limiting its ability to perform its task.
Carrier
In the case of hemochromatosis, a person who carries a mutation in one of the two copies of the HFE gene on chromosome 6 (versus affected persons have mutations in both copies of the HFE gene).
Chromosome
Thread-like structures, contained inside the middle (nucleus) of all our cells, which houses DNA -- our genetic information. Human cells have 23 pairs of chromosomes; we inherit one of each pair from our mother and father. 22 pairs are autosomes and the 23rd pair is the sex chromosomes (X and Y).
Compound Heterozygotes
Individuals who inherit two different mutated versions of the HFE gene, one on each of their chromosomes. Compound heterozygotes usually have a C282Y mutation in one HFE gene copy, and a H63D mutation in the second HFE gene copy.
DNA
Short for deoxyribonucleic acid, DNA is the molecule that encodes all of our genetic information.
Ferritin
A protein that stores iron. High ferritin levels in the blood can be one indication of hemochromatosis.
Gene
A specific portion of DNA that contains instructions for making a specific functional product called a protein.
H63D
A mutation in the HFE gene, which (like the C282Y mutation) results in a change in the amino acid in the protein produced, and affects how the protein 'folds,' thereby limiting its ability to perform its task.
HFE
The gene on chromosome 6 that encodes the HFE protein. People with Type 1 hereditary hemochromatosis have abnormal HFE proteins due to mutations in the HFE gene.
HHC
Abbreviation for hereditary hemochromatosis.
Heterozygotes
The technical term for a carrier, describing individuals who have inherited one normal and one mutated version of the same gene, one on each of their chromosomes.
Homozygotes
Individuals who have inherited two identical mutations in a gene, one on each of their chromosomes.
Phlebotomy
Bloodletting, the common treatment for hemochromatosis.
Transferrin
A protein that circulates in the bloodstream and binds to iron thus "ferrying" iron to other parts of the body. Transferrin is normally 30% bound to iron.
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Genetic Inheritance
This page is also available as a printable PDF: Genetic Inheritance 
Inheritance Combinations for HFE Hemochromatosis (Autosomal Recessive Inheritance)
If both parents are carriers of one C282Y mutation for the HFE-hemochromatosis gene, for each pregnancy there is a 25% chance of inheriting two normal copies of the gene and being unaffected, a 50% chance of inheriting one mutated copy and one normal copy and being a carrier, and a 25% chance of inheriting two mutated copies and being affected.
If one parent is affected with two copies of the C282Y mutation for the HFE-hemochromatosis gene, and the other parent is unaffected, there is a 100% chance that each pregnancy will inherit one mutated copy and one normal copy, which means that all offspring will be obligate carriers.
If one parent is affected with two copies of the C282Y mutation for the HFE-hemochromatosis gene, and the other parent is a carrier for one C282Y mutation, for each pregnancy there is a 50% chance of inheriting one mutated copy and one normal copy and being a carrier, and a 50% chance of inheriting two mutated copies and being affected.
If one parent is affected with two copies of the C282Y mutation for the HFE-hemochromatosis gene, and the other parent is a carrier for one H63D mutation, for each pregnancy there is a 50% chance of inheriting one mutated C282Y copy and one normal copy and being a carrier, and a 50% chance of inheriting two mutated copies (one C282Y and one H63D) and being affected.
If one parent is affected with two mutated copies (one C282Y and one H63D) for the HFE-hemochromatosis gene, and the other parent is unaffected, there is a 100% chance that each pregnancy will inherit one mutated copy and one normal copy, which means that all offspring will be obligate carriers. 50% of the offspring will be C282Y carriers and 50% of the offspring will be H63D carriers.
If one parent is affected with two mutated copies (one C282Y and one H63D) for the HFE-hemochromatosis gene, and the other parent is a carrier for one C282Y mutation, for each pregnancy: there is a 50% chance of inheriting one mutated copy (either one C282Y or one H63D) and one normal copy and being a carrier, and a 50% chance of inheriting two mutated copies (either two C282Y copies, or one C282Y and one H63D) and being affected.
If one parent is affected with two mutated copies (one C282Y and one H63D) for the HFE-hemochromatosis gene, and the other parent is a carrier for one H63D mutation, for each pregnancy: there is a 50% chance of inheriting one mutated copy (either one C282Y or one H63D) and one normal copy and being a carrier, and a 50% chance of inheriting two mutated copies (either two H63D copies, or one C282Y and one H63D) and being affected.
Types of Hemochromatosis
| Type 1 | Type 2A | Type 2B | Type 3 | Type 4 | |
| Name | Classic HHC | Juvenile HHC | Juvenile HHC | TfR2-related HHC | Ferroportin-related iron overload |
| Gene | HFE | HJV | HAMP | TfR2 | SLC40A1 |
| Protein Produced | HFE | Hemojuvelin | Hepcidin | Transferrin receptor 2 | Ferroportin (iron regulatory protein) |
| Inheritance | autosomal recessive | autosomal recessive | autosomal recessive | autosomal recessive | autosomal dominant |
| Function | interruption of transferrin-bound iron, possible modulation of hepcidin regulation | unknown; possible hepcidin modulation | regulation of iron release in intestinal and blood cells | possible interference of iron uptake by liver cells | possible interference of iron export from intestinal, liver and placental cells |
| Organ Damage | variable | high | high | variable | low |
| Decade of Onset | 4th or 5th | 2nd or 3rd | 2nd or 3rd | 4th or 5th | 4th or 5th |
Adapted from New England Journal of Medicine, 350; 23, June 3, 2004: Classifications as defined by OMIM (Online Mendelaian Inheritance in Man)
There may be other as yet unknown functions related to iron overload. The listed functions do not, at least at this time, always account for the known pathophysiological features associated with gene mutation.
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