Diagnosis of Smith-Lemli-Opitz syndrome from stored filter paper blood specimens

Background-Smith-Lemli-Opitz (SLO) syndrome is a recessively inheritable me tabolic disease with deficiency of cholesterol and accumulation of dehydroc holesterols, caused by a defect in the last step of cholesterol biosynthesi s. Biochemical methods for identification of affected individuals, even pre natally, have been developed. Reliable genetic counselling is now possible. Aim-To find a method of proving or disproving whether a child in whom SLO s yndrome had been suspected but not confirmed during lifetime had in fact di ed of the SLO syndrome. Methods-Lipid extracts of stored filter paper blood specimens collected at the national neonatal metabolic screening were used . The ratio of dehydrocholesterols to cholesterol was measured by combined gas chromatography-mass spectrometry. Results-The ratio of 8-dehydrocholesterol to cholesterol in stored filter p aper specimens clearly distinguished affected infants fi om normal infants. SLO syndrome was thus proven in two children who had died more than seven years earlier. Conclusion-It is possible to diagnose SLO syndrome from dried paper specime ns, even when the samples were collected more than a decade ago. Genetic co unselling is available for families of affected children who died before th e discovery of the defect in cholesterol synthesis.