Hereditary hemochromatosis

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What is hereditary hemochromatosis?

Hereditary hemochromatosis is a disorder that causes the body to absorb too much iron from the diet. The excess iron is stored in the body's tissues and organs, particularly the skin, heart, liver, pancreas, and joints. Because humans cannot increase the excretion of iron, excess iron can overload and eventually damage tissues and organs. For this reason, hereditary hemochromatosis is also called an iron overload disorder.

Early symptoms of hereditary hemochromatosis are nonspecific and may include fatigue, joint pain, abdominal pain, and loss of sex drive. Later signs and symptoms can include arthritis, liver disease, diabetes, heart abnormalities, and skin discoloration. The appearance and progression of symptoms can be affected by environmental and lifestyle factors such as the amount of iron in the diet, alcohol use, and infections.

Hereditary hemochromatosis is classified by type depending on the age of onset and other factors such as genetic cause and mode of inheritance. Type 1, the most common form of the disorder, and type 4 (also called ferroportin disease) begin in adulthood. Men with type 1 or type 4 hemochromatosis typically develop symptoms between the ages of 40 and 60, and women usually develop symptoms after menopause.

Type 2 hemochromatosis is a juvenile-onset disorder. Iron accumulation begins early in life, and symptoms may appear in childhood. By age 20, decreased or absent secretion of sex hormones is evident. Females usually begin menstruation in a normal manner, but menses stop after a few years. Males may experience delayed puberty or symptoms related to a shortage of sex hormones. If the disorder is untreated, heart disease becomes evident by age 30.

The onset of type 3 hemochromatosis is usually intermediate between types 1 and 2. Symptoms of type 3 hemochromatosis generally begin before age 30.

How common is hereditary hemochromatosis?

Type 1 hemochromatosis is one of the most common genetic disorders in the United States, affecting about 1 million people. It most often affects people of Northern European descent. The other types of hemochromatosis are considered rare and have been studied in only a small number of families worldwide.

What genes are related to hereditary hemochromatosis?

Mutations in the HAMP, HFE, HFE2, SLC40A1, and TFR2 genes cause hereditary hemochromatosis. Type 1 hemochromatosis results from mutations in the HFE gene, and type 2 hemochromatosis results from mutations in either the HFE2 or HAMP gene. Mutations in the TFR2 gene cause type 3 hemochromatosis, and mutations in the SLC40A1 gene cause type 4 hemochromatosis.

The proteins produced from these genes play important roles in regulating the absorption, transport, and storage of iron. Mutations in any of these genes impair the control of iron absorption during digestion and alter the distribution of iron to other parts of the body. As a result, iron accumulates in tissues and organs, which can disrupt their normal functions.

Read more about the HAMP, HFE, HFE2, SLC40A1, and TFR2 genes.

How do people inherit hereditary hemochromatosis?

Types 1, 2, and 3 hemochromatosis are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but do not show signs and symptoms of the condition.

Type 4 hemochromatosis is distinguished by its autosomal dominant inheritance pattern. With this type of inheritance, one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.

Where can I find information about diagnosis or management of hereditary hemochromatosis?

These resources address the diagnosis or management of hereditary hemochromatosis and may include treatment providers.

You might also find information on the diagnosis or management of hereditary hemochromatosis inEducational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about hereditary hemochromatosis?

You may find the following resources about hereditary hemochromatosis helpful. These materials are written for the general public.

MedlinePlus - Health information (2 links)
Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (4 links)
Additional NIH Resources - National Institutes of Health (3 links)
Educational resources - Information pages (11 links)
Patient support - For patients and families (5 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Reviews - Clinical summary (3 links)
Genetic Testing Registry - Repository of genetic test information (4 links)
ClinicalTrials.gov - Linking patients to medical research
PubMed - Recent literature
OMIM - Genetic disorder catalog (4 links)

What other names do people use for hereditary hemochromatosis?

bronzed cirrhosis
bronze diabetes
familial hemochromatosis
genetic hemochromatosis
haemochromatosis
HC
hemochromatosis
hereditary haemochromatosis
HH
HLAH
iron storage disorder
pigmentary cirrhosis
primary hemochromatosis
Troisier-Hanot-Chauffard syndrome
Von Recklenhausen-Applebaum disease

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about hereditary hemochromatosis?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding hereditary hemochromatosis?

arthritis ; autosomal ; autosomal dominant ; autosomal recessive ; cell ; cirrhosis ; congenital ;diabetes ; digestion ; excretion ; familial ; gene ; giant cell ; hepatitis ; hereditary ; inheritance ;inheritance pattern ; inherited ; iron ; joint ; juvenile ; menopause ; menses ; menstruation ;metabolism ; mode of inheritance ; neonatal ; pancreas ; progression ; puberty ; recessive ; secretion ;syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (7 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook