CLINICAL AND BIOCHEMICAL SCREENING FOR SMITH-LEMLI-OPITZ SYNDROME

Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital anomalies/m ental retardation disorder possibly due to a defect of Delta 7-sterol reductase, leading to low plasma cholesterol levels and to the accumul ation of 7-dehydrocholesterol (7-DHC) and other cholesterol precursors . This study aimed to identify clinical features that could potentiall y be specific indicators for the clinical diagnosis of SLOS, and to te st the reliability of ultraviolet spectrophotometry (UVS) as a biochem ical screening procedure for the syndrome. Twenty patients with clinic al suspicion of SLOS, referred to 11 Italian paediatric and clinical g enetic centres, were collected during 1994. In 10 patients the diagnos is was confirmed biochemically by gas chromatography/mass spectrometry (GC/MS) analysis of serum sterols, whereas in the other 10 patients t he serum sterol profiles were normal. A comparison between confirmed S LOS patients and biochemically negative subjects did not show clinical signs specific for the syndrome. UVS measurement of 7-DHC correlated well with GC/MS profiles, showing 100% sensitivity and specificity. Fo ur out of five patients had serum bile acid concentrations below the n ormal range of controls.