Hemochromatosis 2011

Summary

Hemochromatosis is the generally used term if the body stores too much iron. There are two different forms with subtypes of hemochromatosis possible: primary and secondary.

Primary hemochromatosis is usually caused by a genetic problem or mutation, resulting in storing too much iron due malfunction at the regulation of the the iron absorption.

Secondary hemochromatosis can be temporarily acquired if a person is affected by chronic alcoholism or received many blood transfusion in a short time.

This entry is about the primary form and especially type 1 of it. It is a hereditary autosomal recessiv genetic disorder caused by a mutation of the HFE-Gene and the breakdown of the regulation of the iron absorption. It was first described by Armand Trousseau in 1865 in a report about diabetes.

Phenotype

Primary Hemochromatosis occurs at different subtypes, each of them caused by a mutation of a important protein. But all of these have in common that an excess of iron is deposited in different organs leading to their malfunction.

Type 1: HFE-Gene -> hfe protein

Type 2A: hemojuvelin

Type 2B: hepcidin

Type 3: transferrin receptor 2

Type 4: ferroportin

Symptoms:

• decoloration/darkening of skin (also known as bronzening)
• weakness
• fatigue
• heart failure
• diabetis
• arthritis (iron in joints)
• loss of weight
• loss of body hair
• loss of sexual energy
• liver cirrhosis
• liver swelling

Diagnosis

It can be diagnosed by a simple blood test or a liver biopsy. <ref>http://www.nlm.nih.gov/medlineplus/ency/article/000327.htm</ref>

• Blood test: The concentrations of serum ferritin and serum iron and the percentage of transferrin saturation are measured. It's likely to be affected hemochromatosis if these values are all higher than the average/recommend ones. Other blood elements can also be used for diagnosing like the level of blood sugar (glucose) or the concentration of alpha fetoprotein.
• Liver biopsy: During a local anesthetic of the region around the liver is a tiny part of the liver extracted and examined. If the level of the stored iron at the liver is higher than average/recommend values, it is recommend to do a blood test of the protein concentrations.

Treatment

bloodloss(?) ironless diet

Cross-references

The disesase is also described in detail at

• Wikipedia
• HGMD
• OMIM
• PubMed
• MedlinePlus
• NDDIC
• The Hemochromatosis Information Center

Biochemical disease mechanism

Source: http://www.pdb.org/pdb/explore/explore.do?structureId=1A6Z

The HFE-Gene alleviates the binding of transferrin which is the carrier protein for iron in the blood cyclus. With a mutated HFE-Gen, the intestines interpret a strong transferrin signal as an deficient in iron. Therefore the cells start to import iron, which leads to an iron overload.

Gene

The HFE (High Iron FE) gene is located on the short arm of the chromosome number 6 at position 6p21.3.

File:PIC STILL MISSING

Source: http://upload.wikimedia.org/wikipedia/commons/thumb/0/01/Chromosome_6.svg/125px-Chromosome_6.svg.png

Protein

Hfe-protein

Function

regulation of iron absorption in the body

Cross-references

Links to proteins that are involved in causing the disease

• KEGG at Hemochromatosis
• UniProt at Hemochromatosis Protein (HLA-H)
• UniProt at Hepcidin (HAMP)
• UniProt at (Sero)transferrin (TF)
• UniProt at Transferrin receptor protein 1 (TFR)
• UniProt at Transferrin receptor protein 2 (TF2)

Mutations

Current knowledge about mutations associated with the disease. - Separate into disease causing and neutral mutations. -- These sequence pages will be the starting point for collecting prediction results and result discussions.

Reference sequence

Which sequence does not cause the disease and is most often found in the population.

• Create a page for the reference sequence.

Neutral mutations

• Create one page per mutated sequence.

Disease causing mutations

• Create one page per mutated sequence.