Juvenile Hemochromatosis

National Organization for Rare Disorders, Inc.

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It is possible that the main title of the report Juvenile Hemochromatosis is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


  • hereditary hemochromatosis type 2
  • juvenile hereditary hemochromatosis
  • type 2 hereditary hemochromatosis

Disorder Subdivisions

  • None

General Discussion

Juvenile hemochromatosis is a rare genetic disorder characterized by the accumulation of iron in various organs of the body. Symptoms usually become apparent before the age of 30. The specific symptoms and severity of juvenile hemochromatosis vary from one person to another. Common symptoms include absent or decreased function of the testes in males or ovaries in females (hypotrophic hypogonadism), heart (cardiac) disease, scarring of the liver (cirrhosis), joint disease, diabetes, and dark discoloration of patches of skin (hyperpigmentation). These symptoms are similar to those seen in classic hereditary hemochromatosis. However, the symptoms associated with juvenile hemochromatosis occur at an early age and are usually more severe. If untreated, juvenile hemochromatosis can potentially cause life-threatening complications. Juvenile hemochromatosis is caused by mutations of one of at least two genes (the HJV and HAMP genes). These mutations are inherited as an autosomal recessive trait.

Juvenile hemochromatosis is classified as an iron overload disorder. It is a separate, distinct disorder from classic hereditary hemochromatosis. Juvenile hemochromatosis is caused by mutations to different genes and generally has an earlier age of onset and more severe iron accumulation.


The symptoms and severity of juvenile hemochromatosis can vary from one person to another. Major symptoms include hypogonadotropic hypogonadism and heart, liver and joint disease. In some cases, nonspecific, vague symptoms may precede the development of more serious complications. Such symptoms may include fatigue, joint pain (arthralgia), and lack of appetite. If left untreated, juvenile hemochromatosis can progress to cause serious, life-threatening complications.

The symptoms of juvenile hemochromatosis usually become apparent at some point before 30 years of age. However, in rare cases, some individuals have not developed symptoms until their 30s.

Hypogonadotropic hypogonadism, a common symptom associated with juvenile hemochromatosis, is characterized by absent or decreased function of the testes in males or ovaries in females. Hypogonadotropic hypogonadism can result in delays in attaining puberty, loss of sexual hair, impotence in men and a reduction or absence of the menstrual cycle for six months in girls who have already started menstruation (secondary amenorrhea). Lack of a sex drive and infertility may also be associated with this condition. Prolonged hypogonadism can result in low bone density (osteopenia) and fragile bones that are prone to facture (osteoporosis).

Many individuals with juvenile hemochromatosis develop disease of the heart muscle (cardiomyopathy). Heart abnormalities can start suddenly and can quickly progress to cause serious, life-threatening complications including irregular heartbeats (arrhythmias) and heart failure. In some cases, heart disease may be the first noticeable sign of juvenile hemochromatosis.

Additional symptoms potentially associated with juvenile hemochromatosis include a progressive darkening of patches of skin (increased skin pigmentation), joint disease (arthropathy) and liver disease, eventually resulting in enlargement of the liver (hepatomegaly) and scarring (cirrhosis).

Iron accumulation in individuals with juvenile hemochromatosis may also occur in the pancreas. The pancreas is a small organ located behind the stomach that secretes enzymes that travel to the intestines and aid in digestion. The pancreas also secretes other hormones such as insulin, which helps break down sugar. Damage to the pancreas may ultimately lead to diabetes mellitus. Diabetes is a common disorder in which the body does not produce enough or is unable to properly use insulin. Therefore, the body is not able to properly convert nutrients into the energy necessary for daily activities. The most obvious symptoms are unusually excessive thirst and urination.

In rare cases, affected individuals may experience an underactive thyroid (hypothyroidism) or inadequate production of the steroid hormones cortisol and aldosterone by the outer layer of cells of the adrenal glands (adrenocortical insufficiency).


Mutations of two genes (HJV and HAMP) are known to cause juvenile hemochromatosis. Mutations of the HJV gene account for more than 90 percent of known cases of juvenile hemochromatosis. Mutations of the HJV and HAMP genes are inherited as autosomal recessive traits. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females.

Investigators have determined that the hemojuvelin (HJV) gene is located on the long arm (q) of chromosome 1 (1q21) and that the hepcidin antimicrobial peptide (HAMP) gene is located on the long arm (q) of chromosome 19 (19q13). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 1q21" refers to band 21 on the long arm of chromosome 1. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

The HJV gene contains instructions for creating a protein known as hemojuvelin. The HAMP gene contains instructions for creating a protein known as hepcidin. Researchers believe that these proteins are essential for the proper absorption and transport of iron within the body. Mutations of these genes results in deficient levels of functional hemojuvelin or hepcidin, which ultimately results in the accumulation of iron in the liver, heart, and pancreas. Iron accumulation damages the tissue of affected organs causing the characteristic symptoms juvenile hemochromatosis.

Individuals with juvenile hemochromatosis caused by mutations of the HJV gene are sometimes referred to as having juvenile hemochromatosis type 2A. Individuals with mutations in the HAMP gene are sometimes referred to as having juvenile hemochromatosis type 2B. Initial studies have not shown any difference in the clinical phenotype based upon the specific mutation. (Phenotype refers to the physical traits of a person determined by their genetic and environmental factors.)

Most researchers think that juvenile hemochromatosis mutations are 100 percent penetrant, which means that affected individuals who carry mutations to both alleles will exhibit some degree of disease (unlike mutations in the HFE gene which causes adult hemochromatosis). (An allele refers to one of two or more alternative forms of a particular gene.). Some researchers also suspect that additional, as yet unidentified, genetic and possibly environmental factors influence the development and progression of juvenile hemochromatosis in each individual.

Affected Populations

Juvenile hemochromatosis affects males and females in equal numbers. The disorder is rare, but the actual incidence in the general population is unknown. Juvenile hemochromatosis has been reported worldwide. The disorder usually becomes apparent between 10-30 years of age. Mutations of the HJV gene account for the majority of cases of juvenile hemochromatosis.

Standard Therapies


In individuals with juvenile hemochromatosis early diagnosis and prompt treatment are essential and may help to prevent permanent organ damage and potentially life-threatening complications resulting from excessive iron storage. The disorder may be diagnosed based upon a thorough clinical evaluation; detection of certain physical findings (including hepatomegaly, diabetes mellitus, abnormal skin pigmentation, heart disease, hypogonadism, and/or arthritis), a thorough patient history; a complete family history, and specialized tests.

When juvenile hemochromatosis is suspected, blood tests are performed to detect abnormally increased levels of iron in the blood; elevated blood levels of an iron compound that is used as an indicator of the body's iron stores (serum ferritin levels); and increased transferrin saturation. (Transferrin is a protein involved in the transport of iron from the intestine into the bloodstream.)

In addition, specialized imaging tests such as magnetic resonance imaging (MRI) may reveal increased density of the liver due to excessive iron deposition. An MRI uses a magnetic field and radio waves to provide detailed cross-sectional images of certain organs and tissues. A liver biopsy may also be used to aid in diagnosing juvenile hemochromatosis. During a liver biopsy, samples of liver tissue are removed and microscopically examined to detect increased iron storage and the presence of cirrhosis.

A diagnosis of juvenile hemochromatosis can be confirmed through molecular genetic testing, which can reveal characteristic mutations of the HJV or HAMP genes that cause the disorder. Molecular genetic testing is available on a clinical basis.


The treatment of juvenile hemochromatosis is directed toward the specific symptoms that are apparent in each individual. Treatment is generally similar to existing treatment options for classic hemochromatosis. Basically, physicians will remove excess iron from the body through a procedure called a phlebotomy.

Much of the iron in the body is present in red blood cells. Therefore, therapy involves the regular removal of blood via a vein (phlebotomy) to reduce excess iron from within the body. Phlebotomy may be required about once or twice a week. Weekly phlebotomy may continue to be necessary for approximately two to three years because individuals with juvenile hemochromatosis usually experience severe iron overload. Once acceptable levels of iron are achieved, weekly phlebotomy therapy is stopped and maintenance therapy is started. With maintenance therapy, individuals give blood (to reduce iron levels) less frequently than every week. The specific amount required varies, but generally four to six phlebotomies per year are sufficient.

Although iron chelators are often used to treat other disorders of iron overload, they are not recommended for individuals with juvenile hemochromatosis. Iron chelators are drugs that bind to the excess iron in the body allowing it to be dissolved in water and excreted from the body through the kidneys. Deferoxamine is an iron chelator that has been used as an adjunct therapy in individuals with juvenile hemochromatosis who also have anemia or severe cardiac disease.

Early, prompt detection and treatment of juvenile hemochromatosis is essential because it can prevent organ damage and the development of certain secondary complications. Individuals that are diagnosed early in childhood and placed on and stick to phlebotomy programs have a significantly reduced development of secondary complications. Some damage once it occurs is irreversible. Secondary complications that do develop are treated by standard, conventional methods.

Hypogonadotropic hypogonadism can be treated with hormone replacement therapy. Joint pain may be treated with non-steroidal anti-inflammatories (NSAIDs). Heart disease is treated with angiotensin-converting enzyme (ACE) inhibitors, drugs that help remove salt and water from the body (diuretics [water pills]), and drugs called glycosides that are commonly used to treat heart failure and arrhythmias. In some cases, severe, irreversible heart damage has necessitated a heart transplant.

Early signs of liver disease such as (fibrosis) can be treated with phlebotomy. In some individuals with classic hemochromatosis, these symptoms have been reversible. It is not known whether these symptoms are reversible in individuals with juvenile hemochromatosis. Liver cirrhosis is not reversible and requires therapy with propranolol and nadolol, medications that prevent high blood pressure in the main artery of the liver (portal hypertension). In some cases, a liver transplant may become necessary.

Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:




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Canadian Hemochromatosis Society

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For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.