Clinical manifestations of hemochromatosis in HFE C282Y homozygotes identified by screening.
BACKGROUND
Patients with hemochromatosis may suffer organ damage from iron overload, often with serious clinical consequences.


OBJECTIVE
To assess prevalences of self-reported symptoms and clinical signs and conditions in persons homozygous for the hemochromatosis gene (HFE) mutation (C282Y) identified by screening.


METHODS
Participants were adults 25 years of age or older enrolled in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. C282Y homozygotes (n=282) were compared with control participants without the HFE C282Y or H63D alleles (ie, wild type/wild type; n=364).


RESULTS
Previously diagnosed C282Y homozygotes and newly diagnosed homozygotes with elevated serum ferritin levels had higher prevalences of certain symptoms such as chronic fatigue (OR 2.8; 95% CI 1.34 to 5.95, and OR 2.0; 95% CI 1.07 to 3.75, respectively), and had more hyperpigmentation on physical examination (OR 4.7; 95% CI 1.50 to 15.06, and OR 3.7; 95% CI 1.10 to 12.16, respectively) and swelling or tenderness of the second and third metacarpophalangeal joints (OR 4.2; 95% CI 1.37 to 13.03, and OR 3.3; 95% CI 1.17 to 9.49, respectively) than control subjects. Joint stiffness was also more common among newly diagnosed C282Y homozygotes with elevated serum ferritin than among control subjects (OR 2.7; 95% CI 1.38 to 5.30). However, the sex- and age-adjusted prevalences of self-reported symptoms and signs of liver disease, heart disease, diabetes and most other major clinical manifestations of hemochromatosis were similar in C282Y homozygotes and control subjects.


CONCLUSIONS
Some symptoms and conditions associated with hemochromatosis were more prevalent among C282Y homozygotes identified by screening than among control subjects, but prevalences of most outcomes were similar in C282Y homozygotes and controls in this primary care-based study.
McLaren
Gordon D
GD
Department of Veteran's Affairs Long Beach Healthcare Systems, Long Beach, California 90822, USA. gordon.mclaren@va.gov
McLaren
Christine E
CE
Adams
Paul C
PC
Barton
James C
JC
Reboussin
David M
DM
Gordeuk
Victor R
VR
Acton
Ronald T
RT
Harris
Emily L
EL
Speechley
Mark R
MR
Sholinsky
Phyliss
P
Dawkins
Fitzroy W
FW
Snively
Beverly M
BM
Vogt
Thomas M
TM
Eckfeldt
John H
JH
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002170:Canada / Q000453:epidemiology; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006432:Hemochromatosis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000097:blood / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D012307:Risk Factors; D017678:Sex Distribution; D014481:United States / Q000453:epidemiology
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D004247:DNA; D007501:Iron