Clinical utility and outcome of HFE-genotyping in the search for hereditary hemochromatosis.
BACKGROUND
Hereditary hemochromatosis (HH), a disease involving iron accumulation in internal organs, occurs in about 1 in 200-400 Caucasians. The gene mutated in this disorder is termed HFE. The present study was designed to evaluate the diagnostic utility and outcome of genetic testing for HH in the service of public health care.


METHODS
137 subjects were referred by health clinics and general hospitals for HFE genotyping from various parts of Finland during the period 1999-2001. Two major mutations (C282Y and H63D) were determined for each patient. Reasons contributing to referrals and sets of values for serum transferrin saturation (s-TS) and iron and ferritin concentrations were also determined.


RESULTS
16.8% of the subjects were homozygous for the C282Y mutation, together with seven C282Y/H63D compound heterozygotes (5.1%). The rate of positive findings for the most typical mutations responsible for HH was found to have increased steadily during the period 1999-2001.


CONCLUSIONS
Our data support a role for active testing for the C282Y and H63D mutations in health care. The fairly low number of genotyping requests nevertheless suggests that a large number of patients even with typical clinical signs or symptoms continue to escape detection.
Hannuksela
Jokke
J
Department of Clinical Chemistry, P.O. Box 5000, 90014 University of Oulu, Oulu, Finland. jokkeha@paju.oulu.fi
Niemelä
Onni
O
Leppilampi
Mari
M
Parkkila
Anna Kaisa
AK
Koistinen
Pirjo
P
Nieminen
Pentti
P
Parkkila
Seppo
S
D000328:Adult; D002624:Chemistry, Clinical / Q000379:methods; D005260:Female; D005293:Ferritins / Q000097:blood; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000097:blood; D008297:Male; D008403:Mass Screening / Q000379:methods; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation; D012680:Sensitivity and Specificity; D014168:Transferrin / Q000032:analysis / Q000096:biosynthesis
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins; D007501:Iron