Cory Yamashita1, Paul C Adams. 1. Department of Medicine, London Health Sciences Centre, 339 Windermere Road, London, Ontario, Canada N6A 5A5.
Abstract
BACKGROUND & AIMS: The discovery of a genetic test for hereditary hemochromatosis has identified many individuals who are homozygous for the C282Y mutation of the HFE gene with a normal transferrin saturation and serum ferritin level. The long-term prognosis, rate of iron accumulation, and surveillance guidelines for these individuals are unknown. METHODS: To determine the degree of iron accumulation over time, an updated serum ferritin level was obtained in patients initially identified as homozygous for the C282Y mutation with a normal serum ferritin level. RESULTS: Twenty-two asymptomatic untreated C282Y homozygotes with a normal serum ferritin level were identified, 10 through population screening, 9 through pedigree analysis, and 3 through a general medical work-up. There were 18 women (4 postmenopausal) and 4 men with a median age of 46 years, range 28-76 years. The median follow-up interval was 4 years, range 2-23 years. The serum ferritin levels of 20 of 22 patients remained below the upper limit of normal during the follow-up period. A decline in serum ferritin level was observed in 13 of 22 patients. Three patients had an increase in serum ferritin level of greater than 50%, with only 1 male patient exceeding the upper limit of normal by having a serum ferritin level increase from 295 to 344 microg/L during a 3-year period. CONCLUSIONS: In C282Y homozygotes with a normal ferritin level at the time of diagnosis, 20 of 22 patients failed to show any significant increase in serum ferritin level during a median follow-up of 4 years. This has clinical and economic implications for follow-up and surveillance of this selected population.
BACKGROUND & AIMS: The discovery of a genetic test for hereditary hemochromatosis has identified many individuals who are homozygous for the C282Y mutation of the HFE gene with a normal transferrin saturation and serum ferritin level. The long-term prognosis, rate of iron accumulation, and surveillance guidelines for these individuals are unknown. METHODS: To determine the degree of iron accumulation over time, an updated serum ferritin level was obtained in patients initially identified as homozygous for the C282Y mutation with a normal serum ferritin level. RESULTS: Twenty-two asymptomatic untreated C282Y homozygotes with a normal serum ferritin level were identified, 10 through population screening, 9 through pedigree analysis, and 3 through a general medical work-up. There were 18 women (4 postmenopausal) and 4 men with a median age of 46 years, range 28-76 years. The median follow-up interval was 4 years, range 2-23 years. The serum ferritin levels of 20 of 22 patients remained below the upper limit of normal during the follow-up period. A decline in serum ferritin level was observed in 13 of 22 patients. Three patients had an increase in serum ferritin level of greater than 50%, with only 1 male patient exceeding the upper limit of normal by having a serum ferritin level increase from 295 to 344 microg/L during a 3-year period. CONCLUSIONS: In C282Y homozygotes with a normal ferritin level at the time of diagnosis, 20 of 22 patients failed to show any significant increase in serum ferritin level during a median follow-up of 4 years. This has clinical and economic implications for follow-up and surveillance of this selected population.
Authors: Charles D Warne; Sophie G Zaloumis; Nadine A Bertalli; Martin B Delatycki; Amanda J Nicoll; Christine E McLaren; John L Hopper; Graham G Giles; Greg J Anderson; John K Olynyk; Lawrie W Powell; Katrina J Allen; Lyle C Gurrin Journal: J Gastroenterol Hepatol Date: 2017-04 Impact factor: 4.029
Authors: Paul C Adams; David M Reboussin; Richard D Press; James C Barton; Ronald T Acton; Godfrey C Moses; Catherine Leiendecker-Foster; Gordon D McLaren; Fitzroy W Dawkins; Victor R Gordeuk; Laura Lovato; John H Eckfeldt Journal: Am J Med Date: 2007-11 Impact factor: 4.965