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Juvenile Hereditary Hemochromatosis.


Goldberg YP.


GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
2005 Feb 17 [updated 2011 Aug 11].



Juvenile hemochromatosis is characterized by onset of severe iron overload occurring typically in the first to third decades of life. Males and females are equally affected. Prominent clinical features include hypogonadotropic hypogonadism, cardiomyopathy, arthropathy, and liver fibrosis or cirrhosis. Hepatocellular cancer has not been reported. The main cause of death is cardiac disease. If juvenile hemochromatosis is detected early enough and if blood is removed regularly through the process of phlebotomy to achieve iron depletion, morbidity and mortality are greatly reduced.


Serum ferritin concentration ranges from 1000 to 7000 µg/L. Transferrin-iron saturation is typically very high, often reaching 100%. MRI is used as a noninvasive method of quantifying hepatic iron overload. A hepatic iron index of higher than 1.9 on liver biopsy suggests iron overload. The two genes in which mutations are known to cause juvenile hemochromatosis are HJV (HFE2) (locus name HFE2A) encoding hemojuvelin, accounting for more than 90% of cases, and HAMP (HEPC) (locus name HFE2B) encoding hepcidin, accounting for fewer than 10% of cases.


Treatment of manifestations: Phlebotomy for treatment of iron overload is the same as for classic HFE-associated hemochromatosis, i.e., phlebotomy of one unit of blood (~200 mg of iron) one to two times per week for up to two to three years to reduce iron stores to desired levels (serum ferritin concentration below 50 ng/mL and normal transferrin-iron saturation), followed by phlebotomies to maintain normal serum iron studies. Conventional treatment of secondary complications, including hypogonadotropic hypogonadism, arthropathy, cardiac failure, liver disease, diabetes mellitus. Prevention of primary manifestations: Regular phlebotomies until excess iron stores are depleted. Prevention of secondary complications: Hormone replacement therapy (HRT) to prevent osteoporosis. Surveillance: Monitor those at risk with annual measurement of serum ferritin concentration and transferrin-iron saturation starting in early childhood. For those with hepatic cirrhosis, monitor for hepatocellular cancer with biannual abdominal ultrasound examination and serum alpha-fetoprotein concentration. Agents/circumstances to avoid: Alcohol consumption; ingestion of iron-containing preparations and supplemental vitamin C; handling or eating uncooked shellfish or marine fish because of risk of fatal septicemia from the marine bacterium V vulnificus. Evaluation of relatives at risk: Biochemical testing (i.e., serum ferritin concentration and transferrin-iron saturation) or molecular genetic testing in relatives at risk before evidence of organ damage from iron overload; monitor sibs with annual measurement of serum ferritin concentration and transferrin-iron saturation starting in early childhood.


Juvenile hemochromatosis is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an unaffected carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing are possible if both disease-causing mutations have been identified in the family; however, requests for prenatal testing for conditions which (like juvenile hereditary hemochromatosis) do not affect intellect and have effective treatment available are not common.

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