Volume 183 - Issue 4
Familial hypercholesterolaemia: a look back, a look ahead
Authors: John R Burnett, David Ravine, Frank M van Bockxmeer and Gerald F Watts
Med J Aust 2005; 183 (4): 222-223. || doi: 10.5694/j.1326-5377.2005.tb07014.x
Published online: 15 August 2005
Published online: 15 August 2005
John R Burnett,* David Ravine,† Frank M van Bockxmeer,‡ Gerald F Watts§
* Medical Biochemist, Department of Core Clinical Pathology and Biochemistry [corresponding author]; † Medical Geneticist, Medical Genetics Unit; ‡ Director, Cardiovascular Genetics Laboratory; § Physician, Department of Internal Medicine, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847. john.burnettAThealth.wa.gov.au
In reply: The international MEDPED-FH project has made a major contribution towards introducing family-based cascade screening into the Australian health care system. Although these achievements are important, we agree with Hamilton-Craig’s view that they are dwarfed by the magnitude of what now has to be done to deliver to all at-risk relatives the health gains that can be achieved by a proactive program of population screening.
The risk of familial hypercholesterolaemia (FH) for a first-degree relative of an affected index case is 250 times greater than the risk for a member of the general population. The relative cost-efficiency of family-based cascade genetic screening is high, compared with population-wide screening for a dominantly inherited disorder.1,2
We disagree with Hamilton-Craig that DNA diagnosis is an essential component of an effective screening program. Among FH-affected families, biochemical testing has a sensitivity of 95%, and a specificity of 96%.3 The additional diagnostic gain from DNA testing in the context of screening relatives at 50% prior risk is marginal, although of use in determining with certainty whether or not a relative has inherited the family-specific trait.
FH offers a paradigm of best clinical practice for improving health care outcomes for a widening range of “monogenic” disorders with complications that can be avoided or reduced by focused health care provision. The time has come when physicians, cardiologists, paediatricians, biochemists, geneticists, public health physicians, general practitioners and those administering the funding of health care delivery in Australia come together and formulate the changes necessary to allow cascade genetic screening for FH to become part of routine health care.
References
- Krawczak M, Cooper DN, Schmidtke J. Estimating the efficacy and efficiency of cascade genetic screening. Am J Hum Genet 2001; 69: 361-370.
- Leren TP. Cascade genetic screening for familial hypercholesterolemia. Clin Genet 2004; 66: 483-487. 0_CBBGEHCH
- Thorsson B, Sigurdsson G, Gudnason V. Systematic family screening for familial hypercholesterolemia in Iceland. Arterioscler Thromb Vasc Biol 2003; 23: 335-338.