Screening for Hemochromatosis in Asymptomatic Subjects With or Without a Family History | Genetics and Genomics | JAMA Internal Medicine | JAMA Network
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Original Investigation
February 13, 2006

Screening for Hemochromatosis in Asymptomatic Subjects With or Without a Family History

Author Affiliations

Author Affiliations: Queensland Institute of Medical Research (Drs Powell, Ramm, Purdie, Anderson, and Subramaniam, Ms Dixon, and Mr Lincoln), Departments of Gastroenterology and Hepatology (Dr Hewett) and Anatomical Pathology (Dr Searle), Royal Brisbane & Women's Hospital, and Department of Gastroenterology and Hepatology, Princess Alexandra Hospital (Drs Fletcher and Crawford), Brisbane, Australia; the Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia (Dr Allen); and Departments of Gastroenterology (Ms Rodgers and Dr Bassett) and Medical Genetics (Dr Cavanaugh), Canberra Hospital, and the Australian National University (Drs Cavanaugh and Bassett), Canberra, Australia.

Arch Intern Med. 2006;166(3):294-301. doi:10.1001/archinte.166.3.294
Abstract

Background  Hemochromatosis in white subjects is mostly due to homozygosity for the common C282Y substitution in HFE. Although clinical symptoms are preventable by early detection of the genetic predisposition and prophylactic treatment, population screening is not currently advocated because of the discrepancy between the common mutation prevalence and apparently lower frequency of clinical disease. This study compared screening for hemochromatosis in subjects with or without a family history.

Methods  We assessed disease expression by clinical evaluation and liver biopsy in 672 essentially asymptomatic C282Y homozygous subjects identified by either family screening or health checks. We also observed a subgroup of untreated homozygotes with normal serum ferritin levels for up to 24 years.

Results  Prevalence of hepatic iron overload and fibrosis were comparable between the 2 groups. Disease-related conditions were more common in male subjects identified by health checks, but they were older. Hepatic iron overload (grades 2-4) was present in 56% and 34.5% of male and female subjects, respectively; hepatic fibrosis (stages 2-4) in 18.4% and 5.4%; and cirrhosis in 5.6% and 1.9%. Hepatic fibrosis and cirrhosis correlated significantly with the hepatic iron concentration, and except in cases of cirrhosis, there was a 7.5-fold reduction in the mean fibrosis score after phlebotomy. All subjects with cirrhosis were asymptomatic.

Conclusions  Screening for hemochromatosis in apparently healthy subjects homozygous for the C282Y mutation with or without a family history reveals comparable levels of hepatic iron overload and disease. Significant hepatic fibrosis is frequently found in asymptomatic subjects with hemochromatosis and, except when cirrhosis is present, is reversed by iron removal.

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