Hemochromatosis type 4

Title

Other Names:

HFE4; Hemochromatosis, autosomal dominant; Hemochromatosis due to defect in ferroportin; HFE4; Hemochromatosis, autosomal dominant; Hemochromatosis due to defect in ferroportin; Autosomal dominant hereditary hemochromatosis; Ferroportin disease See More

Categories:

Blood Diseases; Congenital and Genetic Diseases; Digestive Diseases; Blood Diseases; Congenital and Genetic Diseases; Digestive Diseases; Metabolic disorders See More

This disease is grouped under:

Hemochromatosis

Summary Summary

Hemochromatosis type 4 (also called ferroportin disease) is a disease in which too much iron builds up in the body. This is also called iron overload. Accumulation of iron in the organs is toxic and can cause organ damage. While many organs can be affected, iron overload is especially likely to affect the liver, heart, and pancreas.^[1] Hemochromatosis type 4 can be further divided into two subtypes:^[2]

Hemochromatosis type 4A
Hemochromatosis type 4B

People with hemochromatosis type 4A might not have any symptoms of the disease. Other individuals may develop liver disease as they get older.^[2] Hemochromatosis type 4B can be associated with fatigue, weakness, and joint pain. Other symptoms may include abdominal pain, loss of sex drive, liver disease, diabetes, heart problems, difficulty breathing, and skin discoloration.^[1]^[3] Symptoms of hemochromatosis type 4B can begin anytime from childhood to adulthood.^[2]^[4] Hemochromatosis type 4 is most common in people of southern European ancestry.^[5]

Hemochromatosis type 4 is caused by genetic changes (mutations or pathogenic variants) to the SLC40A1 gene.^[5]^[6] The disease is inherited in an autosomal dominant manner. A diagnosis of hemochromatosis type 4 is suspected when a doctor observes signs and symptoms of the disease. A doctor may decide to order laboratory tests including a liver biopsy, MRI, or blood test. The diagnosis can be confirmed with genetic testing.^[1] Treatment of hemochromatosis type 4B usually involves reducing iron levels by removing blood (phlebotomy) or iron chelation. These treatments can prevent additional organ damage but typically do not reverse existing damage.^[1] People with hemochromatosis type 4A may not be recommended to have phlebotomy because it can increase the risk for complications such as anemia.^[2]

To learn more about other types of hemochromatosis click on the disease names below:

Last updated: 2/18/2018

Symptoms Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Arthralgia	Joint pain	0002829
Generalized hyperpigmentation		0007440
Increased serum ferritin	Elevated serum ferritin High ferritin level Increased ferritin Increased serum ferritin level [ more ]	0003281
Joint dislocation	Joint dislocations Recurrent joint dislocations [ more ]	0001373
Joint swelling		0001386
Limitation of joint mobility	Decreased joint mobility Decreased mobility of joints Limited joint mobility Limited joint motion [ more ]	0001376
30%-79% of people have these symptoms
Abdominal pain	Pain in stomach Stomach pain [ more ]	0002027
Hepatic steatosis	Fatty infiltration of liver Fatty liver [ more ]	0001397
5%-29% of people have these symptoms
Cirrhosis	Scar tissue replaces healthy tissue in the liver	0001394
Congenital hepatic fibrosis	Excessive buildup of connective tissue and scarring of liver at birth	0002612
Percent of people who have these symptoms is not available through HPO
Anemia	Low number of red blood cells or hemoglobin	0001903
Arrhythmia	Abnormal heart rate Heart rhythm disorders Irregular heart beat Irregular heartbeat [ more ]	0011675
Autosomal dominant inheritance		0000006
Cardiomyopathy	Disease of the heart muscle	0001638
Cataract	Clouding of the lens of the eye Cloudy lens [ more ]	0000518
Fatigue	Tired Tiredness [ more ]	0012378
Glucose intolerance		0001952
Impaired glucose tolerance		0040270
Impotence	Difficulty getting a full erection Difficulty getting an erection Erectile dysfunction [ more ]	0000802
Osteoarthritis	Degenerative joint disease	0002758

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2020

Do you have updated information on this disease? We want to hear from you.

Cause Cause

Hemochromatosis type 4 is caused by genetic changes (mutations or pathogenic variants) in the SLC40A1 gene.^[2] This gene provides the body with instructions to make a protein called ferroportin. Ferroportin helps transport iron throughout the body.^[7] Pathogenic variants in the SLC40A1 gene cause the ferroportin protein to allow the body to absorb too much iron. This causes iron to accumulate in different areas of the body, resulting in the signs and symptoms of hemochromatosis type 4.

Last updated: 2/18/2018

Inheritance Inheritance

Hemochromatosis type 4 is inherited in an autosomal dominant manner.^[2] This means that people with hemochromatosis type 4 have a genetic change (mutation or pathogenic variant) in one copy of the SLC40A1 gene in each cell of the body. We inherit one copy of every gene from our mother and the other from our father. In most cases, a person who has hemochromatosis type 4 inherited the pathogenic variant causing the disease from one of his or her parents.^[2]

When a person with hemochromatosis type 4 has children, each child has a:

50% chance to inherit the pathogenic variant in the SLC40A1 gene
50% chance to inherit the working copy of SLC40A1, meaning he or she will not develop symptoms of hemochromatosis type 4

Hemochromatosis type 4 is a disease that shows reduced penetrance.^[2] This means that some people with pathogenic variants in the SLC40A1 gene never show symptoms of the disease. However, children or other family members who have pathogenic variants causing hemochromatosis type 4 may show symptoms of the disease.^[2]

Last updated: 2/18/2018

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

Treatment for hemochromatosis type 4 depends on whether the affected person has hemochromatosis type 4A or hemochromatosis type 4B. People with hemochromatosis type 4B can be treated similarly to people who have other types of hemochromatosis. Treatment options may include reducing iron levels by removing blood (phlebotomy), iron chelation therapy, dietary changes, and treatment for complications of the disease.^[2]

Treatment for people with hemochromatosis type 4A typically does not involve phlebotomy. This is because people with hemochromatosis type 4A may develop low levels of red blood cells (anemia) if they receive phlebotomy treatments. Instead, people with hemochromatosis type 4A are closely monitored with blood tests to determine if they are having symptoms of the disease and how the disease may best be treated.^[2]^[5]

Dietary recommendations for people with hemochromatosis may include avoiding alcohol and red meat. People with hemochromatosis are not recommended to take iron or vitamin C supplements.^[8]

For more detailed information regarding the treatment of hemochromatosis, please reference the Medscape article about hemochromatosis. You may need to register to view the article, but registration is free.

Last updated: 2/18/2018

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

American Hemochromatosis Society, Inc.
PO Box 950871
Lake Mary, FL 32795
Toll-free: 1–888–655–IRON (4766)
Telephone: 407–829–4488
Fax: 407–333–1284
E-mail: mail@americanhs.org
Website: http://www.americanhs.org
Canadian Hemochromatosis Society
7000 Minoru Boulevard
Suite 285
Richmond British Columbia, V6Y 3Z5 Canada
Toll-free: (877) 223-4766
Telephone: (604) 279-7135
E-mail: office@toomuchiron.ca
Website: http://www.toomuchiron.ca
Haemochromatosis Australia
PO Box 6185
Meridian Plains Qld, 4551 Australia
Telephone: 1300 019 028
E-mail: https://haemochromatosis.org.au/contact-us/
Website: https://haemochromatosis.org.au/
Haemochromatosis Society
PO Box 6356
Rugby Warwickshire , CV21 9PA United Kingdom
Telephone: 03030 401 101
E-mail: helpline@ironoverload.org.uk , office@ironoverload.org.uk
Website: http://haemochromatosis.org.uk/
Iron Disorders Institute Inc.
P.O. Box 4891
Greenville, SC 29608
Fax: 864-292-1878
E-mail: info@irondisorders.org
Website: http://www.irondisorders.org/

Organizations Providing General Support

American Diabetes Association
2451 Crystal Drive
Suite 900
Arlington, VA 22202
Toll-free: 1–800–DIABETES (342–2383)
Fax: 703–549–6995
E-mail: AskADA@diabetes.org
Website: http://www.diabetes.org
American Liver Foundation
39 Broadway, Suite 2700
New York, NY 10006
Toll-free: +1-800-465-4837 (Helpline)
Telephone: +1-212-668-1000
E-mail: https://liverfoundation.org/for-patients/contact-us/
Website: https://liverfoundation.org/

Do you know of an organization? We want to hear from you.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

Good Days provides help to patients with life-altering conditions. Assistance includes help with the cost of medications and travel.
Patient Access Network Foundation (PAN Foundation) has Assistance Programs for those with health insurance who reside in the United States. The disease fund status can change over time, so you may need to check back if funds are not currently available.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Hemochromatosis type 4. This website is maintained by the National Library of Medicine.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Hemochromatosis type 4. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

Hemochromatosis. National Heart, Lung, and Blood Institute (NHLBI). https://www.nhlbi.nih.gov/health-topics/hemochromatosis. Accessed 1/28/2018.
Brissot P. Hemochromatosis type 4. Orphanet. March 2010; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=139491.
Neves J, Leitz D, Kraut S, Brandenberger C, Agrawal R, Weissmann N, Muhlfeld C, Mall MA, Altamura S, and Muckenthaler MU. Disruption of the Hepcidin/Ferroportin Regulatory System Causes Pulmonary Iron Overload and Restrictive Lung Disease. EBioMedicine. June 2017; 20:230-239. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478206/.
Hemochromatosis, Type 4; HFE4. Online Mendelian Inheritance in Man. June 21, 2016; https://www.omim.org/entry/606069.
Hamilton JPA. Hereditary Hemochromatosis. Merck Manual Professional Version. January 2017; http://www.merckmanuals.com/professional/hematology-and-oncology/iron-overload/hereditary-hemochromatosis.
Hereditary hemochromatosis. Genetics Home Reference (GHR). May 2015; https://ghr.nlm.nih.gov/condition/hereditary-hemochromatosis.
SLC40A1 gene. Genetics Home Reference. October 2012; https://ghr.nlm.nih.gov/gene/SLC40A1.
Duchini A, Sfeir HE, and Klachko DM. Hemochromatosis. Medscape. April 4, 2017; http://emedicine.medscape.com/article/177216-overview.