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Disease Profile

Hemochromatosis type 2

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

Childhood

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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

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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

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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.

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

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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.

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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.

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Not applicable

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Other names (AKA)

Juvenile hemochromatosis; Hemochromatosis juvenile; Iron overload disease juvenile;

Categories

Blood Diseases; Congenital and Genetic Diseases; Digestive Diseases;

Summary

Hemochromatosis type 2 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.

Symptoms of hemochromatosis type 2 typically begin during childhood. Early symptoms of hemochromatosis type 2 typically include liver disease, heart disease, and low levels of sex hormones.[1] Having low levels of sex hormones can cause women to stop having their monthly periods and men to have delayed puberty. People with hemochromatosis type 2 may have heart disease by age 30.[2] Other symptoms may include abdominal pain, diabetes, and skin discoloration.[3]

Hemochromatosis type 2 is caused by genetic changes (mutations or pathogenic variants) to the HFE2 (HJV) or HAMP genes.[2][4] The disease is inherited in an autosomal recessive manner. A diagnosis of hemochromatosis type 2 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.[3] Treatment of hemochromatosis type 2 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.[3][5]

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
Congenital hepatic fibrosis
Excessive buildup of connective tissue and scarring of liver at birth
0002612
Elevated transferrin saturation
0012463
Increased serum ferritin
High ferritin level
Elevated serum ferritin
Increased serum ferritin level
Increased ferritin

[ more ]

0003281
30%-79% of people have these symptoms
Arthropathy
Disease of the joints
0003040
Diabetes mellitus
0000819
Dilated cardiomyopathy
Stretched and thinned heart muscle
0001644
Elevated hepatic transaminase
High liver enzymes
0002910
Generalized hyperpigmentation
0007440
Hypogonadism
Decreased activity of gonads
0000135
Impotence
Difficulty getting a full erection
Difficulty getting an erection

[ more ]

0000802
Lethargy
0001254
Muscle weakness
Muscular weakness
0001324
5%-29% of people have these symptoms
Abnormality of endocrine pancreas physiology
0012093
Osteoporosis
0000939
1%-4% of people have these symptoms
Cardiomyopathy
Disease of the heart muscle
0001638
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Hepatomegaly
Enlarged liver
0002240
Hypogonadotropic hypogonadism
0000044
Increased serum iron
0003452
Percent of people who have these symptoms is not available through HPO
Amenorrhea
Abnormal absence of menstruation
0000141
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat

[ more ]

0011675
Arthritis
Joint inflammation
0001369
Autosomal recessive inheritance
0000007
Azoospermia
Absent sperm in semen
0000027
Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure

[ more ]

0001635
Hyperpigmentation of the skin
Patchy darkened skin
0000953
Infertility
0000789
Splenomegaly
Increased spleen size
0001744
Young adult onset
0011462

Cause

Hemochromatosis type 2 is caused by genetic changes (mutations or pathogenic variants) in the HFE2 (also known as HJV) or HAMP genes. The HAMP gene provides instructions to the body to make a protein called hepcidin. Hepcidin controls iron absorption in the small intestine. Pathogenic variants in the HAMP gene cause hepcidin to not be able to limit iron absorption when there is already too much iron in the body.[6] The HFE2 (HJV) gene is thought to provide instructions to the body to help regulate hepcidin. Pathogenic variants in the HFE2 (HJV) gene, cause this protein to not be able to regulate hepcidin.[7] Therefore, pathogenic variants in either of these genes cause iron to accumulate in tissues and organs, which can result in organ damage.[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 2 may include reducing iron levels by removing blood (phlebotomy), iron chelation therapy, dietary changes, and treatment for complications of the disease. The goal of treatment is to reduce the amount of iron in the body to normal levels, prevent or delay organ damage from excess iron, and maintain normal amounts of iron throughout the lifetime.[3]

    Phlebotomy helps to remove excess iron from the body. Most people begin treatment with weekly therapeutic phlebotomy, although sometimes treatment is initially twice a week if iron levels are very elevated. Maintenance phlebotomy usually involves treatment every 2-4 months.[8] Iron chelation therapy may be recommended for some people with hemochromatosis type 2 if they have other health issues. This involves removing excess iron using medications.[8] The use of these therapies to treat hemochromatosis type 2 can greatly reduce the risk of organ damage.[9]

    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] Hormone replacement therapy may be used to replace low sex hormones.[1]

    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

        • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
        • Genetics Home Reference (GHR) contains information on Hemochromatosis type 2. This website is maintained by the National Library of Medicine.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • 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 2. Click on the link to view a sample search on this topic.

            References

            1. Goldberg YP. Juvenile Hereditary Hemochromatosis. GeneReviews. August 11, 2011; https://www.ncbi.nlm.nih.gov/books/NBK1170/.
            2. Hereditary hemochromatosis. Genetics Home Reference (GHR). May 2015; https://ghr.nlm.nih.gov/condition/hereditary-hemochromatosis.
            3. Hemochromatosis. National Heart, Lung, and Blood Institute (NHLBI). https://www.nhlbi.nih.gov/health-topics/hemochromatosis. Accessed 1/28/2018.
            4. Hamilton JPA. Hereditary Hemochromatosis. Merck Manual Professional Version. January 2017; https://www.merckmanuals.com/professional/hematology-and-oncology/iron-overload/hereditary-hemochromatosis.
            5. Gersten T. Hemochromatosis. MedlinePlus. March 16, 2016; https://www.nlm.nih.gov/medlineplus/ency/article/000327.htm.
            6. HAMP gene. Genetics Home Reference. October 2006; https://ghr.nlm.nih.gov/gene/HAMP.
            7. HFE2 gene. Genetics Home Reference. October 2006; https://ghr.nlm.nih.gov/gene/HFE2.
            8. Duchini A, Sfeir HE, and Klachko DM. Hemochromatosis. Medscape. April 4, 2017; https://emedicine.medscape.com/article/177216-overview.
            9. Brissot P. Hemochromatosis type 2. Orphanet. March 2010; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=79230.

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