Clinical and molecular aspects of juvenile hemochromatosis in Saguenay-Lac-Saint-Jean (Quebec, Canada)

We report the clinical, biochemical, and genetic characteristics of 13 hemo chromatosis patients from Saguenay-Lac-Saint-Jean in whom the first symptom s appeared before age 30. Although the mean age at onset of the first sympt oms was 21.5 years, their mean age at diagnosis was 23.8 years; the diagnos is was particularly delayed among women. Seventy-seven percent of the patie nts had hypogonadotrophic hypogonadism and 69% heart failure and/or cardiac arrhythmias. Genetic analysis of the HFE gene revealed heterozygosity for the C282Y mutation in 2 patients and for the S65C mutation in 2 others and homozygosity for the H63D mutation in 1 patient. The remaining 8 patients h ad no identified mutation in the HFE gene, although sequencing of all seven codons and intron- exon junctions was performed (5 patients). All 13 patie nts fulfill the clinical criteria of juvenile hemochromatosis and represent the largest cluster thus far reported. (C) 2000 Academic Press.