Searching for Hereditary Hemochromatosis

Abstract

OBJECTIVE: To detect hereditary hemochromatosis (HH) in low-income residents of a medically underserved region through free screening and confirmatory laboratory testing and to raise awareness of HH in the general population.

DESIGN: Two-tiered reflexive laboratory testing was used to screen for HH. Participants evaluated the project by written survey upon its conclusion. Data were analyzed by descriptive techniques.

SETTING: Local public health departments in 18 counties in western North Carolina (WNC).

PARTICIPANTS/SUBJECTS: Phase 1: adult volunteers age ≥ 20 without previous diagnosis of HH; Phase 2: Phase 1 participants with elevated screening results and adult family members of Phase 2 participants found to have HFE mutations; Phase 3: randomly-selected Phase 1 participants (Survey A) and all Phase 2 participants with HFE mutations (Survey B).

INTERVENTIONS: Phase 1 (initial screening): non-fasting blood collection by venipuncture with testing for transferrin saturation (TS). Phase 2 (confirmatory testing): fasting blood collection by venipuncture for TS, serum ferritin (SF), and cheek swab for DNA analysis for two HFE mutations (C282Y and H63D). Phase 3: written Surveys A and B.

MAIN OUTCOME MEASURES: Total number participants screened for HH; prevalence of elevated TS in Phase 1 participants; prevalence of HFE genotypes consistent with HH (C282Y/C282Y and C282Y/H63D) in Phase 2 participants; prevalence of elevated SF in subjects with HFE mutations; number of family members tested; number of participants being treated for HH as a result of screening; increase in awareness of HH among Phase 1 participants.

RESULTS: 2,034 total subjects participated in screening events and/or family member testing. Of the 1,976 Phase 1 participants, 130 (6.6%) had elevated TS (≥ 45%). Twenty of 130 (15.4%) Phase 2 subjects were homozygotes for C282Y. The prevalence of the C282Y/C282Y genotype among the Phase 1 participants who were tested in Phase 2 was 20/1976 (1.0%). Fourteen of 20 (70%) C282Y homozygotes had elevated SF. Eleven of 130 (8.5%) Phase 2 subjects were compound heterozygotes for C282Y and H63D, and none had elevated SF. Of 58 family members tested, two (3.4%) were homozygotes for C282Y and eight (13.8%) were compound heterozygotes for C282Y and H63D. One of two (50%) family members homozygous for C282Y had an elevated SF. No compound heterozygotes had elevated SF. Sixty-four of 120 (54.2%) Phase 1 subjects responded to Survey A. 53.1% of respondents were unaware of HH prior to the screening event. 92.1% of respondents told their family and friends about HH after participating. 73.4% discussed their laboratory results with their healthcare provider. Twenty of 41 participants (48.8%) found to have HFE mutations associated with HH responded to Survey B. Eleven of 20 (55.0%) stated that they were being treated for HH.

CONCLUSION: The prevalence of the major genetic mutation, C282Y/C282Y, associated with HH among Phase 1 study participants in WNC was 1%, more than three times the national prevalence of approximately 0.33%. Results suggest that free screening using laboratory tests in a two-tiered reflexive approach may be an effective means of detecting HH, especially in high-risk populations. Early detection through free laboratory screening tests may reduce morbidity and, ultimately, healthcare costs for low-income individuals. Awareness of HH as a health concern may increase as a result of publicity generated by screening events.

ABBREVIATIONS: HESP = Hemochromatosis Education and Screening Project; HH = hereditary hemochromatosis; PHD = public health department; SF = serum ferritin; SI = serum iron; TIBC = total iron binding capacity; TS = transferrin saturation; WNC = western North Carolina.