PITFALLS IN MEASURING PLASMA-CHOLESTEROL IN THE SMITH-LEMLI-OPITZ SYNDROME

Correct quantitative results for plasma cholesterol, 7-dehydrocholeste rol (7-DHC), and 8-dehydrocholesterol (8-DHC) are invaluable for makin g the correct diagnosis in patients with the Smith-Lemli-Opitz syndrom e (SLO) and for biochemical monitoring of these patients during therap y. The enzymatic method for cholesterol measurement based on cholester ol oxidase gives falsely high values for plasma cholesterol in samples from patients with SLO. Both 7-DHC and 8-DHC contribute substantially to the test result, given that they are accepted substrates of choles terol oxidase. All cholesterol methods making use of this enzyme are e xpected to give unreliable results with plasma samples from SLO patien ts. Cholesterol values found with these methods may be low-normal in i ndividual cases with SLO. Therefore, other techniques for measuring ch olesterol, 7-DHC, and 8-DHC, e.g., gas chromatography, should be used for diagnosing these patients and for follow-up during therapy. Howeve r, a normal value for plasma cholesterol, as obtained by gas chromatog raphy, does not exclude SLO. The diagnosis should always be confirmed or excluded by testing for the presence of high concentrations of 7-DH C and 8-DHC in plasma. We found that one patient with a severe form of the disease had a plasma cholesterol concentration of 20 mu mol/L-to our knowledge, the lowest value ever recorded in a human being.