Genetic test in screening for hereditary hemochromatosis

Findings by SBU Alert

This is a translation of version 1, published on June 6, 2000. The latest version of this report is not available in English.

Hemochromatosis is the most common hereditary disease in Sweden. It is caused by two mutations of a gene. People who inherit a mutation from each parent are double carriers (homozygous or compound heterozygous). These individuals have a higher absorption of iron from their diet. With years, the increased amount of iron that is stored in the body may result in severe organ damage. A simple therapy is available through regular bleeding. This procedure removes toxic iron and is especially effective if the condition is detected early.

When the disease is suspected, a diagnosis is established through genetic testing for hereditary hemochromatosis. The examination involves a simple blood test which, in most cases, replaces a liver biopsy that was previously used for the diagnosis. This test is also used to examine family members of
patients with hemochromatosis.

Since hemochromatosis is common and can be successfully treated, screening by genetic testing could be an effective method to detect the disease at an early stage. Hence, serious complications could be prevented.

The extent to which screening for hemochromatosis can result in health benefits is yet unclear. Severity of the disease varies widely among patients with hemochromatosis. It is therefore uncertain how many of the diagnosed patients will develop a severe disease and would benefit from early diagnosis and treatment. This is the main reason why genetic screening in the general population cannot be recommended at this time.

Currently, there is poor* scientific documentation on the advantages and disadvantages of general screening for hereditary hemochromatosis by genetic testing. There is no* scientific documentation on the long-term consequences of such screening or its cost effectiveness.

Until scientific assessments of screening programs for hereditary hemochromatosis become available,routine screening should not be introduced in Sweden, except within the framework of scientific studies. Since the iron tablets that are distributed after blood donation are a potentially toxic medication in hemochromatosis, initial studies should look at the consequences of screening blood donors.

*This assessment by SBU Alert uses a 4-point scale to grade the quality and evidence of the scientific documentation. The grades indicate: (1) good, (2) moderate, (3) poor, or (4) no scientific evidence on the subject.

This summary is based on a report prepared at SBU in collaboration with Assoc. Prof. Sigvard Olsson, Sahlgrenska University Hospital, Göteborg. It has been reviewed by Assoc. Prof. Rolf Hultcrantz, Karolinska Hospital, Stockholm and Assoc. Prof. Ulf Kristoffersson, Lund Universtity Hospital, Lund.

The complete report is available in Swedish only.

Alert is a joint effort by the Swedish Council on Technology Assessment in Health Care (SBU), the Medical Products Agency, the National Board of Health and Welfare, and the Federation of Swedish County Councils.

References

1. Adams PC, Barton J, Bradley LA et al Population screening for hemochromatosis - overview from a consensus panel. J.Hepatol 2000,Sept
2. Beckman LE, Beckman L. Hereditär hemokromatos. Genfynd ger nya behandlingsmöjligheter. Läkartidningen 1997;94:3961-62.
3. Burke W, Thomson E, Khoury MJ, Mc Donnell SM et al. Hereditary hemochromatosis: gene discovery and its implications for population-based screening. JAMA 1998;280:172-8.
4. Cardoso EMP, Stål P, Hagen K, Cabeba JM, Esin S, De Sousa M, Hultcrantz R. HFE mutations in patients with hereditary haemochromatosis. J Intern Med 1998;243:203-208.
5. Feder JN, Gnirke A, Thomas W et al. A novel MHC class I-like gene is mutated in patients with hereditary hemochromatosis Nature Genet. 1996; 13:399-408.
6. Haddow JE, Bradley LA. Hereditary haemochromatosis: to screen or not. Editorial. BMJ 1999;319:531-532.
7. Jouanolle AM, Moirand R, Deugnier Y, Olivier C, et al. Preliminary study before systematic screening of hemochromatosis in Brittany: Penetrance of C282Y homozygosity and serum index levels. Abstract 254, Bioiron 99,Sorrento, Italy 1999.
8. Konar J, Högh Dufva I, Olsson KS, Raha Chowdhury R, Erlandsson R. Screening for Hemochromatosis before the age of 35. Time to accept these donors at blood banks? Abstract 242. Bio Iron Meeting,Sorrento 1999 .
9. Olsson KS. Prevalence of haemochromatosis in Scandinavia. In Hallberg L, Asp NG, eds. Iron Nutrition in Health and Disease. John Libbey & Co 1996:273-277.
10. Olynyk JK, Cullen DJ, Aquilia S, Rossi E, Summerville S, Powell LW. A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med 1999;341:718 ?724.
11. Wiggers P, Dalhöj J, Kiaer H et al. Screening for hemochromatosis: prevalence among Danish blood donors. J Intern Med 1991;230:265.
12. Åsberg A, Hweem K, Thorstensen K, Bjerve K. Genotyping of 566 individuals with suspected hemochromatosis. Abstract 239. Bio Iron Meeting,Sorrento 1999.