RT Book, Section A1 Gulley, Margaret L. A2 Reisner, Howard M. SR Print(0) ID 1115278805 T1 Clinical Practice: Molecular Pathology T2 Pathology: A Modern Case Study YR 2015 FD 2015 PB McGraw-Hill Education PP New York, NY SN 9780071621564 LK accessmedicine.mhmedical.com/content.aspx?aid=1115278805 RD 2024/03/29 AB A 30-year-old man developed liver cirrhosis and diabetes. Laboratory studies showing high serum ferritin and high transferrin saturation led to the hypothesis that iron toxicity to the liver and pancreas contributed to his cirrhosis and diabetes. A blood specimen was tested for mutation in the HFE gene that is responsible, at least in part, for hereditary hemochromatosis. Polymerase chain reaction (PCR) followed by melt curve analysis was performed, and a pathologist interpreted the findings as HFE C282Y mutation without wild-type DNA at that locus. Homozygous HFE gene mutation with the predicted amino acid substitution predisposes to iron overload by overabsorption of iron from the diet. He was treated with therapeutic phlebotomy until his serum iron levels returned to the normal range. He remains at risk for iron overload, and he should be periodically monitored and managed accordingly. A genetic counselor educated him about the increased risk of iron overload faced by blood relatives if they, too, inherited two mutated alleles of the HFE gene.