Hereditary hemochromatosis: laboratory evaluation

Area of Science:

• Clinical Biochemistry
• Genetics
• Hepatology

Background:

• Hereditary hemochromatosis (HH) is characterized by iron overload resulting from genetic abnormalities in iron metabolism.
• Clinical laboratories are essential for diagnosing, validating, and monitoring HH.
• Elevated iron markers can indicate HH but also other liver conditions.

Purpose of the Study:

• To outline the diagnostic and monitoring roles of clinical laboratories in hereditary hemochromatosis.
• To discuss the utility and limitations of HFE gene testing in HH diagnosis.
• To highlight alternative diagnostic approaches for HH cases without HFE mutations.

Main Methods:

• Review of diagnostic markers including serum iron, transferrin saturation, and ferritin.
• Discussion of HFE gene mutation analysis as a primary diagnostic tool.
• Consideration of advanced imaging (MRI) and liver biopsy for iron quantification.

Main Results:

• Elevated iron markers suggest HH but require exclusion of secondary causes.
• HFE gene testing confirms HH in most cases, but 5-15% of phenotypic HH patients lack HFE mutations.
• MRI or liver biopsy are indicated for diagnosing HH in HFE-negative individuals.

Conclusions:

• Clinical laboratories are pivotal in the multi-faceted approach to diagnosing and managing hereditary hemochromatosis.
• While HFE gene testing is key, alternative diagnostic strategies are necessary for a subset of patients.
• The role of hepcidin in HH diagnosis and management remains under investigation due to its complex functions.