HEMOCHROMATOSIS

Disease

Brief Summary

Haemochromatosis is a congenital condition that is characterized by excessive intestinal absorption of dietary iron, resulting in a pathological increase in total body iron stores. The disorder is a systemic iron overload of genetic origin, caused by either a reduction in the concentration of the iron regulatory hormone hepcidin, or a reduction in hepcidin-ferroportin binding.

Image:

Phlebotomy procedure

Frequency

A most common form of this condition is called type 1 hemochromatosis which affects about

1, 000, 000 individuals in the United States. It more commonly affects people from Northern European descent. The other types of such conditions are rare and have been studied in a few families worldwide.

Further details here.

Inheritance

History of Disease

A study was conducted of 96 pedigrees where upon observation Hemochromatosis was seen as an autosomal recessive inheritance. One form of Hemochromatosis is inherited as an autosomal dominant disorder with incomplete penetrance in females due to loss of blood during menstruation and pregnancy.

The first known case of Hemochromatosis was presented in 1865 by the French doctor Trousseau. He described a new syndrome involving diabetes, pigmented liver cirrhosis and bronze-coloured skin, which he later referred to as “bronze diabetes”.

In 1935, English doctor Sheldon's groundbreaking book entitled Haemochromatosis provided a retrospective review of 311 patient cases and put forward the idea that haemochromatosis was a congenital metabolic disorder.

Pathogenesis

Most types of primary hemochromatosis are caused by HFE gene mutations. The HFE gene controls how much iron you absorb from food. If a person has primary hemochromatosis, he/she probably inherited the mutated gene from both of his/her parents.

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.

Brief Summary

History of Disease

Pathogenesis

Image:

Hemochromatosis pathogenesis chart

Frequency

Symptoms

Hemochromatosis clinical symptoms often occur after significant iron accumulation, usually after the age of 40. Due to the loss of iron during menstruation in women, symptoms emerge earlier in males than in females. The following are some of the symptoms of Hemochromatosis:

joint and abdominal pain

fatigue

weakness and weight loss

Impotence and loss of sex drive

Bronze or gray skin color

Heart and liver failure

Diabetes

Memory fog

Social Concerns

Hereditary hemochromatosis (HH) is one of the most common genetic illnesses in the United States, but it takes an average of 9.5 years for the condition to be diagnosed. Treatment and management of the condition are very simple and can considerably improve the results of HH patients. However, HH genotyping is often misinterpreted. An inaccurate diagnosis of hereditary hemochromatosis can be a distraction that prevents the actual cause of abnormal iron study results from being identified, consequently delaying effective treatment. Delayed diagnosis of Hereditary hemochromatosis increases health problems, healthcare expenses, and morbidity rates in patients.

Treatment

Available Clinical Treatments

Therapeutic Phlebotomy

This is a technique that removes blood (and iron) from the body. A needle is inserted into a vein, and the blood flows through a sealed tube into a sterile container or bag.

Iron Chelation Therapy

Iron chelation therapy is the use of medication to eliminate excess iron from the body. This procedure is a suitable alternative for patients who cannot have routine blood removal.

Other Treatment Products/Options

Hemochromatosis Supplements

While not a replacement for conventional treatments like phlebotomy, there are many remedies from the natural world that may help patients feel better and improve their overall health with hemochromatosis including Turmeric, Quercetin, and Resveratrol.

Lifestyle and Home Remedies

In addition to blood removal, patients may further reduce the risk of complications from hemochromatosis by: avoiding iron supplements and multivitamins containing iron, avoiding vitamin C supplements, avoiding alcohol, and avoiding raw fish and shellfish.

Updates on Clinical Trials

Title: Analysis of the Modulation of Serum Hepcidin Level in Response to Iron Oral Intake: Potential Interest for the Differential Diagnosis Between Ferroportin Disease and Dysmetabolic Hepatosiderosis

Intervention: Drug: iron fumarate

Goal: The dynamic response of iron parameters, including modulation of hepcidin level, to an iron intake will allow to discriminate patients with ferroportin disease or dysmetabolic hepatosiderosis, situations whose clinicobiological presentation is often confusing.

Further details here.

Title: Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis

Intervention:

Procedure: First evaluation phase : no intervention

Second evaluation phase: bloodletting of 7 ml/kg (with a maximum of 500ml)

Goal: The demonstration of an adverse effect of bloodletting upon iron metabolism would allow for a therapeutic innovation based upon an association of bloodletting and oral chelation during the induction treatment of type 1 hemochromatosis and, more generally in hepcidino deficient forms of hemochromatosis.

Further details here.

Title: HEPFER-Evaluation of a New Phenotypic Biological Marker in Genetic Type 1 Hemochromatosis

Goal: The goal of the project is to determine the intra-individual variations of the H / F ratio over time during maintenance therapy and to assess the correlation with the IRI. HFE(High iron FE)-related hereditary hemochromatosis has a highly variable penetrance. No phenotypic or genetic markers can predict the disease. The Iron Reabsorption Index (IRI), recently described by the group, corresponds to the daily reabsorbed iron for a subject whose iron stock is stable and less than 50 µg / L.

Further details here.

Expert Directory

John Ignatius G. Ledesma, M.D.

Gastroenterology

Location:

Riverside Medical Center, B S Aquino Drive, Bacolod, 6100

Contact No:

(034) 433 7331

Expert Directory

References

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