A review of Hereditary hemochromatosis, a disease resulting in an excess of iron stored in the body, potentially resulting in liver and other organ damage.
Gastroenterology
InShort
by David Payne, MD and David Kauvar, MD
Hereditary hemochromatosis- homozygote or heterozygote, what is the difference?
Hereditary hemochromatosis is one of the most common inherited disorders in individuals of which descent?
Hereditary hemochromatosis (HH) is a disease resulting in an excess of iron stored in the body, potentially resulting in damage to the liver, pancreas, skin, heart, bones, and testes. The most common form stems from mutations in the homeostatic iron regulator (HFE) gene. It is inherited in an . . .
Hereditary Hemochromatosis Signs and Symptoms
Hemochromatosis is often discovered as an incidental finding on routine laboratory evaluation. The most common initial complaints for hemochromatosis are nonspecific and include fatigue, arthritis, and impotence. In the later stages of the disease, however, patients may suffer from a wide and variable array of disease manifestations, including heart failure, cirrhosis, hepatocellular carcinoma, diabetes, abdominal pain, and, more rarely, bronze skin.
The disease tends to noticeably affect adults > 40 years of age. Women may have delayed onset before menopause, as menstruation causes iron loss.
Diagnostic Evaluation
Diagnosis of hemochromatosis depends on elevated iron stores and confirmation via testing for mutations in the HFE gene. Elevated ferritin (men: >300 ng/mL; women: > 200 ng/mL) and/or elevated transferrin saturation ≥ 45% meet laboratory criteria for diagnosis. When testing for genetic mutations, the gene mutation is referred to as C282Y; as an autosomal recessive disease, it is a homozygous mutation in most patients. In the event of elevated ferritin and transferrin saturation and heterozygous C282Y status, referral to a gastroenterologist or hematologist for further workup, including liver biopsy, is warranted. Polycythemia may or may not be associated with hemochromatosis.
Treatment Options
The standard of care to treat hemochromatosis is phlebotomy, with the goal of reducing ferritin levels to normal levels (50-150 ng/mL). Depending on disease severity, phlebotomy schedule ranges from one or two 500-mL units of blood removed per week to one 500-mL unit of blood removed every 6 months. Use of iron supplements and vitamin-C supplements should be avoided.
Efforts to reduce absorption include avoiding a heavy intake of iron-rich foods. Turmeric may help chelate iron from the body, and drinking coffee and especially tea may decrease absorption. However, in essentially all cases, phlebotomy remains necessary.
The sequelae of hemochromatosis include diabetes mellitus, liver cirrhosis, hepatocellular carcinoma, and cardiomyopathy. Therefore, the treatment of severe hemochromatosis may require consultation from a multispecialty medical team.
Prognosis
Prognosis of hemochromatosis appears to be closely linked to development of liver cirrhosis. Prompt diagnosis and treatment may reverse or reduce the severity of diabetes, cardiomyopathy, and hepatic fibrosis, but cirrhosis cannot be reversed. If cirrhosis is present, mortality risk is greatly elevated (50% higher mortality risk over 5 years as compared with noncirrhotic hemochromatosis patients). Early detection and treatment can completely prevent any excess mortality caused by hemochromatosis.
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PHOTO CREDIT: Jose Luis Calvo
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initially published December 2, 2021