Clinical Penetrance of Hereditary Hemochromatosis-Related End-Organ Damage of C282Y Homozygosity, A Newfoundland Experience
Hereditary hemochromatosis is an autosomal recessive disorder of iron absorption, leading to organ dysfunction. C282Y gene homozygosity is implicated in 80%–95% of cases of hereditary hemochromatosis. The clinical penetrance of this genotype remains unclear. The purpose of the study was to better de...
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ftpubmed:oai:pubmedcentral.nih.gov:7665264 2023-05-15T17:21:50+02:00 Clinical Penetrance of Hereditary Hemochromatosis-Related End-Organ Damage of C282Y Homozygosity, A Newfoundland Experience Lim, Dennis R. Vidyasankar, Gokul Phua, Chai Borgaonkar, Mark 2020-11-12 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665264/ https://doi.org/10.14309/ctg.0000000000000258 en eng Wolters Kluwer http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665264/ http://dx.doi.org/10.14309/ctg.0000000000000258 © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. CC-BY-NC-ND Clin Transl Gastroenterol Article Text 2020 ftpubmed https://doi.org/10.14309/ctg.0000000000000258 2020-11-22T01:35:36Z Hereditary hemochromatosis is an autosomal recessive disorder of iron absorption, leading to organ dysfunction. C282Y gene homozygosity is implicated in 80%–95% of cases of hereditary hemochromatosis. The clinical penetrance of this genotype remains unclear. The purpose of the study was to better describe the clinical penetrance and disease progression of C282Y homozygotes. METHODS: This is a retrospective study of all individuals in Newfoundland and Labrador, Canada, homozygous for the C282Y mutation from 1999 to 2009. Using electronic health records, laboratory values, phlebotomy status, radiologic reports, and clinic records were recorded up to November 2017. Iron overload status was classified via the HealthIron study. SPSS Version 19.0 (IBM Corporation) was used for descriptive statistics. Predictors of disease penetrance were assessed with logistic regression; a Student t test was used for continuous variables, and χ(2) tests were used for categorical variables. RESULTS: Between 1999 and 2009, 360 individuals tested positive for C282Y/C282Y. The mean age of diagnosis was 49.1 years. Three hundred six individuals had adequate follow-up for analysis (mean 11.6 years). End-organ damage was observed in 18.3%, with 5.8% developing liver disease. End-organ damage was more frequently observed in men 24.3% vs 10.5% (P < 0.05). Clinical penetrance in postmenopausal women approached that of men 18.3%. DISCUSSION: This is the largest reported cohort of C282Y homozygotes, followed for an extended duration of time in North America. The findings reflect outcomes in routine clinical practice and suggest that C282Y homozygosity uncommonly causes end-organ damage and liver disease. Text Newfoundland PubMed Central (PMC) Canada Newfoundland Clinical and Translational Gastroenterology 11 11 e00258 |
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Article Lim, Dennis R. Vidyasankar, Gokul Phua, Chai Borgaonkar, Mark Clinical Penetrance of Hereditary Hemochromatosis-Related End-Organ Damage of C282Y Homozygosity, A Newfoundland Experience |
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Hereditary hemochromatosis is an autosomal recessive disorder of iron absorption, leading to organ dysfunction. C282Y gene homozygosity is implicated in 80%–95% of cases of hereditary hemochromatosis. The clinical penetrance of this genotype remains unclear. The purpose of the study was to better describe the clinical penetrance and disease progression of C282Y homozygotes. METHODS: This is a retrospective study of all individuals in Newfoundland and Labrador, Canada, homozygous for the C282Y mutation from 1999 to 2009. Using electronic health records, laboratory values, phlebotomy status, radiologic reports, and clinic records were recorded up to November 2017. Iron overload status was classified via the HealthIron study. SPSS Version 19.0 (IBM Corporation) was used for descriptive statistics. Predictors of disease penetrance were assessed with logistic regression; a Student t test was used for continuous variables, and χ(2) tests were used for categorical variables. RESULTS: Between 1999 and 2009, 360 individuals tested positive for C282Y/C282Y. The mean age of diagnosis was 49.1 years. Three hundred six individuals had adequate follow-up for analysis (mean 11.6 years). End-organ damage was observed in 18.3%, with 5.8% developing liver disease. End-organ damage was more frequently observed in men 24.3% vs 10.5% (P < 0.05). Clinical penetrance in postmenopausal women approached that of men 18.3%. DISCUSSION: This is the largest reported cohort of C282Y homozygotes, followed for an extended duration of time in North America. The findings reflect outcomes in routine clinical practice and suggest that C282Y homozygosity uncommonly causes end-organ damage and liver disease. |
format |
Text |
author |
Lim, Dennis R. Vidyasankar, Gokul Phua, Chai Borgaonkar, Mark |
author_facet |
Lim, Dennis R. Vidyasankar, Gokul Phua, Chai Borgaonkar, Mark |
author_sort |
Lim, Dennis R. |
title |
Clinical Penetrance of Hereditary Hemochromatosis-Related End-Organ Damage of C282Y Homozygosity, A Newfoundland Experience |
title_short |
Clinical Penetrance of Hereditary Hemochromatosis-Related End-Organ Damage of C282Y Homozygosity, A Newfoundland Experience |
title_full |
Clinical Penetrance of Hereditary Hemochromatosis-Related End-Organ Damage of C282Y Homozygosity, A Newfoundland Experience |
title_fullStr |
Clinical Penetrance of Hereditary Hemochromatosis-Related End-Organ Damage of C282Y Homozygosity, A Newfoundland Experience |
title_full_unstemmed |
Clinical Penetrance of Hereditary Hemochromatosis-Related End-Organ Damage of C282Y Homozygosity, A Newfoundland Experience |
title_sort |
clinical penetrance of hereditary hemochromatosis-related end-organ damage of c282y homozygosity, a newfoundland experience |
publisher |
Wolters Kluwer |
publishDate |
2020 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665264/ https://doi.org/10.14309/ctg.0000000000000258 |
geographic |
Canada Newfoundland |
geographic_facet |
Canada Newfoundland |
genre |
Newfoundland |
genre_facet |
Newfoundland |
op_source |
Clin Transl Gastroenterol |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665264/ http://dx.doi.org/10.14309/ctg.0000000000000258 |
op_rights |
© 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
op_rightsnorm |
CC-BY-NC-ND |
op_doi |
https://doi.org/10.14309/ctg.0000000000000258 |
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Clinical and Translational Gastroenterology |
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11 |
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11 |
container_start_page |
e00258 |
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1766107676028174336 |