Screening for familial hypercholesterolaemia

British Medical Journal, April 28, 2001 by Brian Tomlinson, Irene Wei Lan, Ian Hamilton-Craig, Paul Nicholls, Ian Young, Kelly Lyttle, Colin Graham

Funding is difficult to obtain but screening can be international

EDITOR--Bhatnagar et al highlighted the cost effective approach of screening family members of probands with the dominant condition of familial hypercholesterolaemia to identify affected relatives at high risk for atheromatous vascular disease.[1] We would like to raise three additional points.

Firstly, patients with clinical features of familial hypercholesterolaemia are often not given an accurate diagnosis unless they come to the attention of a physician interested in lipid disorders. Examination of the Achilles tendons for xanthoma is often overlooked during the routine physical examination, even in patients with very high plasma concentrations of cholesterol and obvious xanthelasmata or prominent premature corneal arcus, so that the precise clinical diagnosis of familial hypercholesterolaemia, with the implications for family screening, may not be made.

Even cardiologists who have a direct interest in the consequences of the disease may not diagnose it because of a preoccupation with the acute events, intervention procedures, and rapid transfer or discharge of patients before plasma concentrations of cholesterol are available.[2] All doctors should therefore be aware of the familial nature of this condition so that probands can be identified and referred to specialist lipid clinics or other facilities that can undertake family screening.

Secondly, although this type of screening is cost effective, it remains difficult to obtain funding.[3] In Hong Kong we screened more than 300 family members of probands for a postgraduate degree study without any specific funding except for a research grant for genetic studies in a subgroup of these patients.[4] Funding for such activities should be available from government health services as this saves costs in the long term, but many health service providers may not regard this as a priority, especially as the treatment of affected subjects will result in an increase in short term expenditure on drug budgets.

Lastly, the screening of family members does not have to be restricted by national boundaries in these days of rapid easy communication. About half of the families we screened had members living in other countries, and members of an extended family in Hong Kong and Singapore have been identified with the same mutation. This approach to the identification of subjects with genetic disease was championed by the late Professor Roger Williams, who initiated the MEDPED (make early diagnosis, prevent early deaths) organisation.[5] Currently more than 28 countries have enrolled over 25 000 patients with familial hypercholesterolaemia in a major international collaboration funded by various international healthcare agencies and pharmaceutical companies to identify subjects with this serious but treatable genetic condition.

Brian Tomlinson professor btomlinson@cuhk.edu.hk

Irene Wei Lan research assistant Division of Clinical Pharmacology, Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region, China

Ian Hamilton-Craig chairman, MEDPED (Asia-Pacific) North Adelaide, South Australia 5006, Australia

The MEDPED Australia website is www.medpedaust.com

[1] Bhatnagar D, Morgan J, Siddiq S, Mackness MI, Miller JP, Durrington PN. Outcome of case finding among relatives of patients with known heterozygous familial hypercholesterolaemia BMJ 2000;321:1497-500. (16 December.)

[2] Dorsch MF, Lawrance RA, Durham NP, Hall AS. Familial hypercholesterolaemia is underdiagnosed after AMI. BMJ 2001;322:111. (13 January.)

[3] Neil HAW, Hammond T, Huxley R, Matthews DR, Humphries SE. Extent of underdiagnosis of familial hypercholesterolaemia in routine practice: prospective registry study. BMJ 2000;321:148.

[4] Mak YT, Pang CP, Tomlinson B, Zhang J, Chan YS, Mak TW, et al. Mutations in the low-density lipoprotein receptor gene in Chinese familial hypercholesterolemia patients. Arterioscl Throm Vas 1998;18:1600-5.

[5] Williams RR, Schumacher MC, Barlow GK, Hunt SC, Ware JL, Pratt M, Latham BD. Documented need for more effective diagnosis and treatment of familial hypercholesterolemia according to data from 502 heterozygotes in Utah. Am J Cardiol 1993;72:18D-24D.

Early identification and treatment of patients is important

EDITOR--Familial hypercholesterolaemia is the commonest single gene disorder, thought to affect about one in 500 of the population in the United Kingdom. It is treatable with statins. As Bhatnagar et al point out in their study,[1] the risk of developing cardiovascular disease in affected people is far higher than the Framingham data would suggest. For affected men aged 30-50, the risk is almost 100-fold compared with unaffected men.[2] Early identification and treatment of such patients is important, and their subsequent treatment is likely to be efficient in preventing early onset coronary heart disease and thus highly cost effective. The best place to start is in already defined family groups.