Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive congenital malformation syndrome caused by mutations in the 7-dehydrocholesterol reductase gene. This inborn error of cholesterol synthesis leads to elevated concentrations of 7-dehydrocholesterol (7-DHC). 7-DHC also serves as the precursor for vitamin D synthesis. Limited data is available on vitamin D levels in individuals with SLOS. Due to elevated concentrations of 7-DHC, we hypothesized that vitamin D status would be abnormal and possibly reach toxic levels in patients with SLOS. Through a retrospective analysis of medical records between 1998 and 2006, we assessed markers of vitamin D and calcium metabolism from 53 pediatric SLOS patients and 867 pediatric patients who were admitted to the NIH Clinical Center (NIHCC) during the same time period. SLOS patients had significantly higher levels of 25(OH)D (48.06 ± 19.53 ng/ml, p < 0.01) across all seasons in comparison to the NIHCC pediatric patients (30.51 ± 16.14 ng/ml). Controlling for season and age of blood draw, 25(OH)D levels were, on average, 15.96 ng/ml (95%CI 13.95-17.90) higher in SLOS patients. Although, mean calcium values for both patient cohorts never exceeded the normal clinical reference range (8.6-10.2 mg/dl), the levels were higher in the SLOS cohort (9.49 ± 0.56 mg/dl, p < 0.01) compared to the NIHCC patients (9.25 ± 0.68 mg/dl). Overall, in comparison to the control cohort, individuals with SLOS have significantly higher concentrations of 25(OH)D that may be explained by elevated concentrations of serum 7-DHC. Despite the elevated vitamin D levels, there was no laboratory or clinical evidence of vitamin D toxicity.
Keywords: 7-dehydrocholesterol; Smith-Lemli-Opitz syndrome; metabolic disorder; vitamin D.
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