Clinical characteristics of HFE C282Y/H63D compound heterozygotes identified in a specialty practice: key differences from HFE C282Y homozygotes

Department

Oncology and Hematology

Additional Department

Internal Medicine

Document Type

Article

Publication Title

Expert Review of Hematology

Abstract

Background: Patients with p.C282Y homozygous (p.C282Y) HFE mutations are more likely to develop hemochromatosis (HC) than p.C282Y/p.H63D compound heterozygotes (p.C282Y/H63D).

Research design and methods: We conducted a retrospective chart review of 90 p.C282Y and 31 p.C282Y/H63D patients at a referral practice to illustrate the differences in the natural history of the disease in these two HC cohorts.

Results: Over a median follow-up of 17 years, p.C282Y had higher mean serum ferritin (1105 mg/dL vs. 534 mg/dL, p = 0.001) and transferrin saturations (75.3% vs. 49.5%, p = 0.001) at diagnosis. p.C282Y underwent more therapeutic phlebotomies (TP) till de-ironing (mean 24 vs. 10), had higher mean mobilized iron stores (4759 mg vs. 1932 mg), and required more annual maintenance TP (1.9/year vs. 1.1/year, p = 0.039). p.C282Y/H63D were more likely to have obesity (45.2% vs. 20.2%, p = 0.007) at diagnosis, with a non-significant trend toward consuming more alcohol. There was no significant difference in the development of HC-related complications between the two cohorts.

Conclusions: p.C282Y have a higher mobilizable iron and require more TP. p.C282Y/H63D likely require additional insults such as obesity or alcohol use to develop elevated ferritin. De-ironing may mitigate the risk of developing HC-related complications.

First Page

145

Last Page

152

DOI

10.1080/17474086.2024.2337950

Volume

17

Issue

4-5

Publication Date

4-1-2024

Medical Subject Headings

Humans; Hemochromatosis Protein (genetics); Hemochromatosis (genetics, diagnosis, therapy); Heterozygote; Female; Male; Homozygote; Middle Aged; Retrospective Studies; Adult; Ferritins (blood); Aged; Mutation; Iron (metabolism); Histocompatibility Antigens Class I (genetics)

PubMed ID

38551816

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