Biochemical and Clinical Effects of Vitamin E Supplementation in Hungarian Smith-Lemli-Opitz Syndrome Patients

Biomolecules. 2021 Aug 17;11(8):1228. doi: 10.3390/biom11081228.


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 supplementation 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 baseline, 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 concentration in all patients. We observed reduced aggression, self-injury, irritability, hyperactivity, attention deficit, repetitive behavior, sleep disturbance, skin photosensitivity and/or eczema in 3/6 patients, 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.

Keywords: Smith-Lemli-Opitz syndrome; behavioral disturbance; skin photosensitivity; vitamin A; vitamin E.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Antioxidants / metabolism
  • Behavior
  • Child
  • Child, Preschool
  • Cholesterol, Dietary / metabolism
  • Chromatography, High Pressure Liquid
  • Chromatography, Liquid
  • Dehydrocholesterols / blood
  • Dietary Supplements*
  • Female
  • Humans
  • Lipids / chemistry
  • Male
  • Oxidative Stress
  • Oxidoreductases Acting on CH-CH Group Donors / genetics
  • Oxysterols / metabolism
  • Prospective Studies
  • Smith-Lemli-Opitz Syndrome / blood*
  • Smith-Lemli-Opitz Syndrome / therapy*
  • Sterols / chemistry
  • Tandem Mass Spectrometry
  • Vitamin A / metabolism
  • Vitamin E / metabolism
  • Vitamin E / therapeutic use*
  • Young Adult


  • Antioxidants
  • Cholesterol, Dietary
  • Dehydrocholesterols
  • Lipids
  • Oxysterols
  • Sterols
  • Vitamin A
  • Vitamin E
  • 7-dehydrocholesterol
  • Oxidoreductases Acting on CH-CH Group Donors
  • 7-dehydrocholesterol reductase