The full content of Annals is available to subscribers

Subscribe/Learn More  >
Articles |

HFE Genotype in Patients with Hemochromatosis and Other Liver Diseases

Bruce R. Bacon, MD; John K. Olynyk, MD; Elizabeth M. Brunt, MD; Robert S. Britton, PhD; and Roger K. Wolff, PhD
[+] Article, Author, and Disclosure Information

From Saint Louis University School of Medicine, St. Louis, Missouri; Fremantle Hospital, Fremantle, Australia; and Progenitor, Inc., Menlo Park, California.

Ann Intern Med. 1999;130(12):953-962. doi:10.7326/0003-4819-130-12-199906150-00002
Text Size: A A A

Background: Hereditary hemochromatosis is a common inherited disorder of iron metabolism. The gene HFE, which contains two missense mutations (C282Y and H63D), was recently identified.

Objective: To determine how HFE genotyping for the C282Y and H63D mutations contributes to the diagnosis of hemochromatosis and to determine the prevalence of HFE mutations in a group of patients with liver disease.

Design: Cross-sectional study.

Setting: Academic medical center.

Patients: 66 patients with hereditary hemochromatosis and 132 referred patients with other liver diseases.

Measurements: At initial diagnosis, fasting transferrin saturation, ferritin level, routine chemistry panel, and complete blood count were determined. Percutaneous liver biopsy was done on all patients for histologic analysis and measurement of hepatic iron concentration and hepatic iron index. HFE genotyping for the C282Y and H63D mutations was done on all patients by using genomic DNA samples.

Results: Of the 66 patients with hemochromatosis diagnosed on the basis of serum iron studies and liver biopsy findings, 60 (91%) were C282Y homozygotes, 2 (3%) were compound heterozygotes, 1 (1.5%) was a C282Y heterozygote, 2 (3%) were H63D heterozygotes, and 1 (1.5%) was negative for both mutations. Of the 132 patients with liver disease, 6 (5%) were C282Y homozygotes, 8 (6%) were compound heterozygotes, 6 (5%) were C282Y heterozygotes, 5 (4%) were H63D homozygotes, 20 (15%) were H63D heterozygotes, and 87 (66%) were negative for both mutations. All 66 C282Y homozygotes had an elevated hepatic iron concentration, and 65 of the 66 patients (98%) had a transferrin saturation of at least 45%. Ten of the 66 patients (15% [95% CI, 7.5% to 26%]) had a hepatic iron index less than 1.9 mmol/kg per year; hemochromatosis was not suspected in 6 of the 10 patients before genotyping. Cirrhosis or substantial hepatic fibrosis was not seen in any (0% [CI, 0% to 18%]) of the 19 patients younger than 40 years of age who were homozygous for the C282Y mutation.

Conclusions: All 66 patients homozygous for the C282Y mutation of HFE had an elevated hepatic iron concentration, but approximately 15% of these patients did not meet a previous diagnostic criterion for hemochromatosis (hepatic iron index > 1.9 mmol/kg per year). Determination of HFE genotype is clinically useful in patients with liver disease and suspected iron overload and may lead to identification of otherwise unsuspected C282Y homozygotes.


Grahic Jump Location
Figure 1.
Hepatic iron concentration (top) and hepatic iron index (bottom) according toHFEgenotype.

Iron concentrations are expressed on a logarithmic scale; the median value for each group is shown. Hepatic iron index values greater than 5 are shown using a compressed scale. To convert µg/g to mmol/kg, multiply by 0.0179. wt = wild-type.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Proposed algorithm for the evaluation of possible hereditary hemochromatosis in a person with a negative family history.

ALT = alanine aminotransferase; AST = aspartate aminotransferase; wt = wild-type.

Grahic Jump Location




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).


Submit a Comment/Letter
Submit a Comment/Letter

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.


Buy Now for $32.00

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Related Articles
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.