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Umans-Eckenhausen et al report, in The Lancet, the results of a five-year study in which they tested for familial hypercholesterolaemia (FH) mutations among 5442 relatives of 237 people who had a known FH-associated mutation in the LDL receptor gene [Umans-Eckenhausen, M.A.W. et al (2001) Lancet 357, 165-168]. Initially, first-degree relatives of the index cases were tested and then, in turn, any additional first degree relatives of those people. 2039 people were identified as heterozygous for an FH-associated mutation. Of these, 69% already knew of their condition and were receiving treatment, and most of the remainder are now also being treated with cholesterol-lowering drugs. The authors compared DNA analysis with measurement of blood cholesterol for diagnosis of FH and conclude that 18% of mutation carriers would have been misdiagnosed on the basis of blood cholesterol alone. Similarly, there would have been 18% "false positives" among non-mutation carriers.

Comment: This study shows that case-finding among relatives of people with FH is an effective way of identifying people with FH, many of whom may be presymptomatic. The same conclusion was reached recently by a UK study, and in an HTA report (see article in December 2000 newsletter). The question remains, however, as to the best means of diagnosing FH. Umans-Eckenhausen recommend DNA analysis as the gold standard. However, this is only feasible if a mutation has been identified in the index case in a family. Moreover, it is uncertain how many of the mutation carriers who did not have raised blood cholesterol would actually go on to develop disease if untreated.