Hereditary Hemochromatosis and Copper Levels
There is no established correlation between hereditary hemochromatosis and abnormal copper levels. Hereditary hemochromatosis is a disorder of iron metabolism caused by HFE gene mutations (primarily C282Y), resulting in excessive iron absorption and deposition in organs such as the liver, heart, and pancreas 1. The disease does not directly affect copper metabolism or copper levels.
Why Copper Is Not Affected in Hemochromatosis
Hereditary hemochromatosis results from inappropriately low hepcidin secretion, which leads to increased duodenal absorption of dietary iron specifically, not other metals like copper 2.
The pathophysiology involves mutations in the HFE gene on chromosome 6p (C282Y mutation in >90% of cases), which disrupts iron regulation through the hepcidin pathway 1.
The clinical manifestations—including cirrhosis, hepatocellular carcinoma, diabetes, and cardiomyopathy—are consequences of iron toxicity in parenchymal cells, not copper accumulation 1.
Important Distinction: Wilson Disease vs. Hemochromatosis
Wilson disease is the hereditary disorder associated with abnormal copper metabolism and copper overload in the liver and other organs, not hemochromatosis 3.
While both hemochromatosis and Wilson disease can cause liver disease, they involve completely different metal pathways and require different diagnostic approaches 3.
Copper chelating agents are used to treat Wilson disease, whereas phlebotomy is the mainstay of treatment for hemochromatosis 3, 2.
Diagnostic Focus in Hemochromatosis
The diagnosis of hemochromatosis relies on documentation of iron overload through elevated transferrin saturation (≥45%) and serum ferritin levels (>200 µg/L in women, >300 µg/L in men), followed by HFE genetic testing 1.
Liver biopsy, when performed, measures hepatic iron concentration, not copper 1, 4.
There is no clinical indication to measure copper levels in patients with suspected or confirmed hereditary hemochromatosis unless there is a separate clinical concern for Wilson disease 3.
Clinical Pitfall to Avoid
- Do not confuse hereditary hemochromatosis (iron overload disorder) with Wilson disease (copper overload disorder)—they are distinct genetic conditions affecting different metals with different inheritance patterns, clinical presentations, and treatments 3.