HFEMutations in Caucasian Participants of the Hemochromatosis and Iron Overload Screening Study with Serum Ferritin Level <1000 μg/L

Abstract

BACKGROUND: Many patients referred for an elevated serum ferritin level &lt;1000 μg/L are advised that they likely have iron overload and hemochromatosis.AIMS: To determine the prevalence ofHFEmutations in the hemochromatosis gene for 11 serum ferritin concentration intervals from 200 μg/L to 1000 μg/L in Caucasian participants in a primary care, population-based study.METHODS: The Hemochromatosis and Iron Overload Screening study screened 99,711 participants for serum ferritin levels, transferrin saturation and genetic testing for the C282Y and H63D mutations of theHFEgene. This analysis was confined to 17,160 male and 27,465 female Caucasian participants because theHFEC282Y mutation is rare in other races. Post-test likelihood was calculated for prediction of C282Y homozygosity from a ferritin interval. A subgroup analysis was performed in participants with both an elevated serum ferritin level and transferrin saturation.RESULTS: There were 3359 male and 2416 female participants with an elevated serum ferritin level (200 μg/L to 1000 μg/L for women, 300 μg/L to 1000 μg/L for men). There were 69 male (2.1%) and 87 female (3.6%) C282Y homozygotes, and the probability of being a homozygote increased as the ferritin level increased. Post-test likelihood values were 0.3% to 16% in men and 0.3% to 30.4% in women.CONCLUSIONS: Iron loadingHFEmutations are unlikely to be the most common cause of an elevated serum ferritin level in patients with mild hyperferritinemia. Patients should be advised that there are many causes of an elevated serum ferritin level including iron overload.

Investigation and management of a raised serum ferritin

“…As a result of iron loss from menstruation and pregnancies, SF values in adult females only start to rise after 50 years of age, to plateau with median values of about 100 μg/l after 60 years. Values >200 μg/l in adult females show a significant age effect and are seen in 3%, 10% and 17% respectively of women aged 30–50 years, 50–70 years and >70 years (Ogilvie et al , ; Adams et al , ).…”

Using iron studies to predict HFE mutations in New Zealand: implications for laboratory testing

“…13,18 The NPV of SF was high overall and thus this marker was effective at ruling out subjects with an unaffected genotype. We found that the Best Practice Advocacy Centre New Zealand (BPACNZ) advice that SF >700 μg/L is an indicator of HH 8 was inaccurate.…”

“…3,5 Although there is strong evidence to justify the need for pre-symptomatic detection of this condition, one of the problems faced by primary care physicians in identifying HH is that symptoms are often absent or mimic those found in other common conditions. 13,14 Previously undiagnosed C282Y homozygotes with SF values that remain <1000 μg/L are at low risk for developing HH signs and symptoms. 9,10 Abnormalities in iron biochemical assays are often the first indicator of HH, and it is widely accepted that transferrin saturation (TS) and SF are the best initial tests for HH.…”

Démarche diagnostique devant une hyperferritinémie

“…L'hyperferritinémie est fréquente, retrouvée chez 13 % des personnes dans une population donnée [11]. Toute hyperferritinémie impose d'en découvrir l'étiologie et de préciser s'il existe un risque de surcharge en fer au niveau de l'organisme.…”

“…Elle est fréquente en Europe occidentale, atteint 2 à 5 ‰ personnes en France, jusqu'à 1 % en Irlande [38]. Dans une population donnée, la mutation homozygote C282Y était retrouvée chez 3 % des personnes ayant une hyperferritinémie [11].…”