Movassaghi Miyad, Bianconi Simona, Feinn Richard, Wassif Christopher A, Porter Forbes D
Frank H. Netter MD School of Medicine at Quinnipiac University, North Haven, Connecticut.
Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda, Maryland.
Am J Med Genet A. 2017 Oct;173(10):2577-2583. doi: 10.1002/ajmg.a.38361. Epub 2017 Aug 10.
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.
史密斯-莱姆利-奥皮茨综合征（SLOS）是一种常染色体隐性先天性畸形综合征，由7-脱氢胆固醇还原酶基因突变引起。这种胆固醇合成的先天性缺陷导致7-脱氢胆固醇（7-DHC）浓度升高。7-DHC也是维生素D合成的前体。关于SLOS患者维生素D水平的数据有限。由于7-DHC浓度升高，我们推测SLOS患者的维生素D状态会异常，甚至可能达到中毒水平。通过对1998年至2006年期间的病历进行回顾性分析，我们评估了53例儿科SLOS患者以及同期入住美国国立卫生研究院临床中心（NIHCC）的867例儿科患者的维生素D和钙代谢指标。与NIHCC儿科患者（30.51±16.14 ng/ml）相比，SLOS患者在所有季节的25(OH)D水平均显著更高（48.06±19.53 ng/ml，p<0.01）。在控制采血季节和年龄后，SLOS患者的25(OH)D水平平均高出15.96 ng/ml（95%CI 13.95-17.90）。虽然两个患者队列的平均钙值均未超过正常临床参考范围（8.6-10.2 mg/dl），但SLOS队列（9.49±0.56 mg/dl，p<0.01）的钙水平高于NIHCC患者（9.25±0.68 mg/dl）。总体而言，与对照组相比，SLOS患者的25(OH)D浓度显著更高，这可能是由于血清7-DHC浓度升高所致。尽管维生素D水平升高，但没有实验室或临床证据表明存在维生素D中毒。
