What is Hereditary Hemochromatosis (HH)?

From the Guidelines

Hereditary Hemochromatosis (HH) is a genetic disorder of iron metabolism characterized by tissue injury resulting from an abnormal accumulation of iron in various organs.

Key Characteristics

• It is usually a consequence of an increased absorption of iron from the gastrointestinal tract, which results in increased iron deposition in tissue, particularly in the liver, heart, and pancreas 1.
• If left untreated, it can lead to organ damage, such as cirrhosis, as well as hepatocellular cancer.
• The mutation of C282Y in the HFE gene on chromosome 6 is present in almost 90% of those affected, and most patients are homozygous, with mutation transmission being autosomal recessive 1.

Diagnosis and Treatment

• Diagnosis of hereditary hemochromatosis is usually based on a combination of various genetic or phenotypic criteria, including direct DNA testing for the 2 HFE gene mutations (C282Y and H63D) and phenotypic markers such as percentage of transferrin saturation and serum ferritin level 1.
• Treatment of hereditary hemochromatosis typically involves phlebotomy, with one phlebotomy (removal of 500 mL of blood) weekly or biweekly, and monitoring of serum ferritin levels to keep them between 25 and 50 ng/mL 1.
• Early identification and preemptive treatment of those at risk can significantly reduce the morbidity and mortality of HH, and institution of phlebotomy therapy before cirrhosis and/or diabetes develop is recommended 1.

From the Research

Definition and Characteristics of Hereditary Hemochromatosis (HH)

• Hereditary Hemochromatosis (HH) is an autosomal recessive genetic disease characterized by an excessively increased absorption of dietary iron 2.
• It is one of the most common genetic disorders in individuals of European descent, leading to toxic effects due to the accumulation of excess iron 2.
• The disease is associated with mutations in the HFE gene, which affects the normal activity of hepcidin, a negative regulator of iron homeostasis 2, 3.

Clinical Presentation and Diagnosis

• Clinical onset of HH symptoms occurs more frequently in adult men than women, as menstrual blood loss in women slows down iron accumulation 2.
• The diagnosis of HH is established by genetic testing in patients with elevated transferrin saturation values 3.
• Ferritin levels greater than 300 ng per mL for men and 200 ng per mL for women and transferrin saturations greater than 45% are highly suggestive of HH 4.

Treatment and Management

• Therapeutic phlebotomy is the primary form of treatment for HH, combined with the use of chelating agents 2.
• Phlebotomy can help improve heart function, reduce abnormal skin pigmentation, and lessen the risk of liver complications 4.
• Liver transplantation may be considered in select patients with advanced cirrhosis 2, 4.

Complications and Prognosis

• If left untreated, HH can lead to morbidity and eventually death, with the most frequent causes of death being liver cancer, cirrhosis, cardiomyopathy, and diabetes 2, 3.
• Early detection and treatment can significantly improve life expectancy and prevent the development of clinical symptoms, particularly cirrhosis 2.
• Individuals with HH have an increased risk of hepatocellular carcinoma and colorectal and breast cancers 4.