Biochemical and clinical effects of vitamin e supplementation in hungarian smith‐lemli‐opitz syndrome patients

Smith‐Lemli‐Opitz syndrome (SLOS) is a severe monogenic disorder resulting in low cholesterol and high 7‐dehydrocholesterol (7‐DHC) levels. 7‐DHC‐derived oxysterols likely contribute to disease pathophysiology, and thus antioxidant treatment might be beneficial because of high oxidative stress. In a three‐year prospective study, we investigated the effects of vitamin E supple-mentation in six SLOS patients already receiving dietary cholesterol treatment. Plasma vitamin A and E concentrations were determined by the high‐performance liquid chromatography (HPLC) method. At baseline, plasma 7‐DHC, 8‐dehydrocholesterol (8‐DHC) and cholesterol levels were determined by liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method. The clinical effect of the supplementation was assessed by performing structured parental interviews. At base-line, patients were characterized by low or low–normal plasma vitamin E concentrations (7.19–15.68 μmol/L), while vitamin A concentrations were found to be normal or high (1.26–2.68 μmol/L). Vitamin E supplementation resulted in correction or significant elevation of plasma vitamin E concen-tration in all patients. We observed reduced aggression, self‐injury, irritability, hyperactivity, atten-tion deficit, repetitive behavior, sleep disturbance, skin photosensitivity and/or eczema in 3/6 pa-tients, with notable individual variability. Clinical response to therapy was associated with a low baseline 7‐DHC + 8‐DHC/cholesterol ratio (0.2–0.4). We suggest that determination of vitamin E status is important in SLOS patients. Supplementation of vitamin E should be considered and might be beneficial.