Overview
Definition
An autosomal recessive disorder of iron metabolism characterized by increased intestinal iron absorption, leading to progressive iron deposition and organ damage in parenchymal tissues.
Epidemiology
Most common autosomal recessive disorder in Caucasians (Northern European descent, carrier rate ~1 in 10).
Etiology & Risk Factors
- Homozygous mutations in the HFE gene (C282Y/C282Y is most common, leads to decreased hepcidin levels)
Clinical Symptoms
- Fatigue and joint pain (specifically MCP joints)
- 'Bronze diabetes' (hyperpigmentation + diabetes)
- Hepatomegaly / Cirrhosis
- Cardiomyopathy (restrictive or dilated) / Arrhythmias
- Hypogonadism (due to pituitary iron deposition)
Clinical Approach
Diagnosis
- Screening: Transferrin saturation (>45%) and elevated ferritin
- Genetic testing for HFE mutations
- MRI of liver/heart to quantify iron overload
- Liver biopsy showing Perl's Prussian blue staining
Management
- Therapeutic Phlebotomy (removal of blood weekly to target ferritin <50-100 mcg/L)
- Iron-chelating agents (Deferasirox, Deferoxamine) if phlebotomy is contraindicated
Complications
- Liver Cirrhosis
- Hepatocellular Carcinoma (highest risk if cirrhosis present)
- Diabetes Mellitus
- Heart Failure