BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.