Clinical and biochemical variability of the classical smith-lemli-opitz syndrome in Egyptians

ABSTRACT

Smith-Lemli-Opitz syndrome [SLO] is the first true metabolic malformation syndrome. The underlying defect is absent or deficient activity of 7-dehydrocholesterol reductase, which is the enzyme catalyzing the last step of cholesterol synthesis. We report on the first Egyptian cases [seven males] with SLO. We studied the clinical and biochemical variability of the syndrome and its relation to patients' age. Mental retardation, 2/3 toe syndactyly and genital anomalies were present in all patients. The distinct facial appearance became less obvious with age. All patients had marked elevation of plasma 7-dehydrocholesterol, which were measured by use of ultraviolet spectrometry. Plasma cholesterol measured by calorimetric method, were within the low normal range in most patients. Dietary cholesterol supplementation in two patients resulted in improvement of behaviour, better tolerance of infection, diminution of photosensitivity, pubertal progression and improvement in plasma sterol levels. The clinical phenotype of SLO is widely variable and plasma cholesterol levels are not reliable for detection of the syndrome. Therefore, diagnosis of SLO by demonstrating increased plasma concentrations of 7-dehydrocholesterol using ultraviolet spectrometry is a rapid and reliable method. Increased awareness of SLO is required for early diagnosis and dietary treatment of affected individuals