HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER		Author Keyword(s) Vol Page [Advanced]

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ryan, E Articles by Crowe, J Search for Related Content PubMed PubMed Citation Articles by Ryan, E Articles by Crowe, J Topic Collections Relevant Article

Underdiagnosis of hereditary haemochromatosis: lack of presentation or penetration?

Centre for Liver Disease, Mater Misericordiae Hospital, Dublin 7, Ireland

Correspondence to:
Correspondence to:
Dr J Crowe, Centre for Liver Disease, Mater Misericordiae Hospital, Eccles Street, Dublin 7, Ireland;
liver{at}mater.ie

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 52% combined with a serum ferritin 300 µg/l for men and 200 µg/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.

Keywords: hereditary haemochromatosis; HFE gene; iron indices; penetrance; underdiagnosis

Abbreviations: HH, hereditary haemochromatosis; ALT, alanine aminotransferase; AST, aspartate aminotransferase

Relevant Article

Digest

Ian Forgacs
Gut 2002 51: 1. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				C A McCune, D Ravine, K Carter, H A Jackson, D Hutton, J Hedderich, M Krawczak, and M Worwood Iron loading and morbidity among relatives of HFE C282Y homozygotes identified either by population genetic testing or presenting as patients Gut, April 1, 2006; 55(4): 554 - 562. [Abstract] [Full Text] [PDF]

				D Thorburn, A J Morris, A J Stanley, and P R Mills Underdiagnosis of hereditary haemochromatosis: reflects lack of clinical not biochemical penetrance Gut, March 1, 2003; 52(3): 455 - 455. [Full Text] [PDF]