BACKGROUND: The majority of hereditary haemochromatosis (HH) patients are homozygous for the C282Y mutation in the HFE gene. We have demonstrated a homozygote frequency of 1 in 83 for the C282Y mutation in a retrospective analysis of Irish neonates. However, a fully developed phenotype is not observed at the same frequency clinically, suggesting that a large proportion of Irish HH patients may remain undiagnosed. AIMS: To determine whether underdiagnosis of HH results from the non-specific nature of early symptoms or incomplete penetrance of the C282Y mutation. METHODS: Seventy nine C282Y homozygous individuals identified from family screening for HH and 30 HH probands were investigated. Non-specific symptoms (fatigue, arthropathy, and impotence) and their association with iron indices (transferrin saturation and serum ferritin) and hepatic iron deposition were analysed. RESULTS: We found that 78% of men (mean age 42 years) and 36% of women (mean age 39 years) who were identified as C282Y homozygotes following family screening had iron overload, as defined by a transferrin saturation >or=52% combined with a serum ferritin >or=300 microg/l for men and >or=200 microg/l for women. The frequency of reports of non-specific symptoms in those individuals with iron overload was not significantly different from those who did not have iron overload. CONCLUSIONS: Our findings indicate that underdiagnosis of HH may be due to the non-specific nature of early symptoms and less frequently to the incomplete penetrance of the C282Y mutation.
BACKGROUND: The majority of hereditary haemochromatosis (HH) patients are homozygous for the C282Y mutation in the HFE gene. We have demonstrated a homozygote frequency of 1 in 83 for the C282Y mutation in a retrospective analysis of Irish neonates. However, a fully developed phenotype is not observed at the same frequency clinically, suggesting that a large proportion of Irish HHpatients may remain undiagnosed. AIMS: To determine whether underdiagnosis of HH results from the non-specific nature of early symptoms or incomplete penetrance of the C282Y mutation. METHODS: Seventy nine C282Y homozygous individuals identified from family screening for HH and 30 HH probands were investigated. Non-specific symptoms (fatigue, arthropathy, and impotence) and their association with iron indices (transferrin saturation and serum ferritin) and hepatic iron deposition were analysed. RESULTS: We found that 78% of men (mean age 42 years) and 36% of women (mean age 39 years) who were identified as C282Y homozygotes following family screening had iron overload, as defined by a transferrin saturation >or=52% combined with a serum ferritin >or=300 microg/l for men and >or=200 microg/l for women. The frequency of reports of non-specific symptoms in those individuals with iron overload was not significantly different from those who did not have iron overload. CONCLUSIONS: Our findings indicate that underdiagnosis of HH may be due to the non-specific nature of early symptoms and less frequently to the incomplete penetrance of the C282Y mutation.
Authors: C E McLaren; G J McLachlan; J W Halliday; S I Webb; B A Leggett; E C Jazwinska; D H Crawford; V R Gordeuk; G D McLaren; L W Powell Journal: Gastroenterology Date: 1998-03 Impact factor: 22.682
Authors: Eugénia Cruz; Jorge Vieira; Susana Almeida; Rosa Lacerda; Andrea Gartner; Carla S Cardoso; Helena Alves; Graça Porto Journal: BMC Med Genet Date: 2006-03-01 Impact factor: 2.103
Authors: Barbara de Graaff; Amanda Neil; Kristy Sanderson; Kwang Chien Yee; Andrew J Palmer Journal: Health Qual Life Outcomes Date: 2016-02-29 Impact factor: 3.186
Authors: Eugénia Cruz; Chris Whittington; Samuel H Krikler; Cláudia Mascarenhas; Rosa Lacerda; Jorge Vieira; Graça Porto Journal: BMC Med Genet Date: 2008-11-06 Impact factor: 2.103