Disease Profile

Hemochromatosis type 4

Prevalence ?
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of Onset

All ages

ageofonset-all.svg

ICD-10

E83.1

Inheritance

Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

rnn-autosomaldominant.svg

Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other Names (AKA)

HFE4; Hemochromatosis, autosomal dominant; Hemochromatosis due to defect in ferroportin;

Categories

Blood Diseases; Congenital and Genetic Diseases; Digestive Diseases;

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:

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.

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

[ more ]

0000802
Osteoarthritis
Degenerative joint disease
0002758

Cause

Hemochromatosis type 4 occurs when the SLC40A1 gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[2]

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 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.[7]

    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.

    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

      Organizations Providing General Support

        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

          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.

            References

            1. Hemochromatosis. National Heart, Lung, and Blood Institute (NHLBI). https://www.nhlbi.nih.gov/health-topics/hemochromatosis. Accessed 1/28/2018.
            2. Brissot P. Hemochromatosis type 4. Orphanet. March 2010; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=139491.
            3. 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/.
            4. Hemochromatosis, Type 4; HFE4. Online Mendelian Inheritance in Man. June 21, 2016; https://www.omim.org/entry/606069.
            5. Hamilton JPA. Hereditary Hemochromatosis. Merck Manual Professional Version. January 2017; https://www.merckmanuals.com/professional/hematology-and-oncology/iron-overload/hereditary-hemochromatosis.
            6. Hereditary hemochromatosis. Genetics Home Reference (GHR). May 2015; https://ghr.nlm.nih.gov/condition/hereditary-hemochromatosis.
            7. Duchini A, Sfeir HE, and Klachko DM. Hemochromatosis. Medscape. April 4, 2017; https://emedicine.medscape.com/article/177216-overview.
            8. SLC40A1 gene. MedlinePlus genetics. October 2012; https://medlineplus.gov/genetics/gene/SLC40A1.