Hereditary hemochromatosis: missed diagnosis or misdiagnosis?

Hereditary hemochromatosis is a disorder that can cause iron overload and organ damage. Hereditary hemochromatosis is characterized by mutations in the HFE gene. HFE C282Y homozygotes and compound heterozygotes (C282Y/H63D) are at risk of developing manifestations of hemochromatosis. Abnormal iron study results also occur in many liver and hematologic diseases. The aim of this study was to evaluate the accuracy of diagnosis of hereditary hemochromatosis.

Pertinent clinical and laboratory data, including HFE genotype, were tabulated from the electronic medical records of patients with the International Classification of Diseases 9th Revision code 275, "disorders of iron metabolism," who were seen at a tertiary referral center between January 2002 and May 2012.

HFE genotyping was obtained in only 373 of 601 patients (62%); 200 were C282Y homozygotes or compound heterozygotes. Of the 173 patients with nonhereditary hemochromatosis genotypes, 53% were misdiagnosed with hereditary hemochromatosis and 38% underwent phlebotomy. In two thirds of these cases, the misdiagnosis was made by a nonspecialist. In the remaining 228 patients who were not genotyped, 80 were diagnosed with hereditary hemochromatosis and 64 were phlebotomized. Of patients misdiagnosed with hemochromatosis, 68% had known liver disease and 5% had a hematologic cause of abnormal iron study results.

Abnormal iron study results in patients with nonhereditary hemochromatosis genotypes commonly lead to a misdiagnosis of hereditary hemochromatosis and inappropriate treatment with phlebotomy. This error often is seen in the setting of elevated iron study results secondary to chronic liver diseases. Furthermore, hereditary hemochromatosis is commonly diagnosed and treated without HFE genotyping. We suggest that phlebotomy centers require a documented HFE genotype before initiating phlebotomy.