HFE C282Y homozygotes aged 25-29 years at HEIRS Study initial screening.
We characterized HFE C282Y homozygotes aged 25-29 years in the HEmochromatosis and IRon Overload Screening (HEIRS) Study using health questionnaire responses, transferrin saturation (TfSat), serum ferritin (SF), and HFE genotyping. In eight homozygotes, we used denaturing high-performance liquid chromatography and sequencing to search for HFE2 (= HJV), TFR2, HAMP, SLC40A1 (= FPN1), and FTL mutations. Sixteen of 4,008 White or Hispanic participants aged 25-29 years had C282Y homozygosity (15 White, 1 Hispanic); 15 were previously undiagnosed. Eleven had elevated TfSat; nine had elevated SF. None reported iron overload-associated abnormalities. No deleterious non-HFE mutations were detected. The prevalence of C282Y homozygosity in White or Hispanic HEIRS Study participants aged 25-29 years did not differ significantly from the prevalence of C282Y homozygosity in older White or Hispanic HEIRS Study participants. The prevalences of reports of iron overload-associated abnormalities were not significantly different in these 16 C282Y homozygotes and in HFE wt/wt control participants aged 25-29 years who did not report having hemochromatosis or iron overload. We conclude that C282Y homozygotes aged 25-29 years diagnosed by screening infrequently report having iron overload-associated abnormalities, although some have elevated SF. Screening using an elevated TfSat criterion would fail to detect some C282Y homozygotes aged 25-29 years.
Barton
James C
JC
Southern Iron Disorders Center, Birmingham, Alabama, USA. ironmd@dnamail.com
Acton
Ronald T
RT
Leiendecker-Foster
Catherine
C
Lovato
Laura
L
Adams
Paul C
PC
McLaren
Gordon D
GD
Eckfeldt
John H
JH
McLaren
Christine E
CE
Reboussin
David M
DM
Gordeuk
Victor R
VR
Speechley
Mark R
MR
Reiss
Jacob A
JA
Press
Richard D
RD
Dawkins
Fitzroy W
FW
D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000235:genetics; D001052:Apoferritins; D027682:Cation Transport Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005293:Ferritins / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D019190:Iron Overload / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D011990:Receptors, Transferrin / Q000235:genetics; D000098742:Ferroportin
D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C507433:FTL protein, human; C578702:HAMP protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D000098742:Ferroportin; D005293:Ferritins; D001052:Apoferritins