Smith-Lemli-Optiz syndrome: importance of ophthalmology referral and follow-up.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder caused by mutations in the 7-dehydrocholesterol reductase (DHCR7) gene, located on chromosomal region 11q13. This results in reduced cholesterol and increased 7-dehydrocholesterol (7DHC) levels. Accumulation of 7DHC in patients with SLOS can affect multiple organs and display a broad phenotypic expression. Ophthalmic abnormalities related to SLOS are variable but the most common is blepharoptosis. Over 50% of these patients present with self-injurious behavior, such as head banging, which can result in ocular complications and blindness. We report the first case of peripheral avascularity of the retina in a patient with SLOS. Physicians should be aware of the potential ocular complications associated with SLOS and confounding factors, such as prematurity, given that referral is usually delayed due to the lack of awareness of these potentially blinding associations. This case highlights the importance of early referral and continuous ophthalmologic follow-up in preventing further deterioration of visual development and complications that can lead to blindness.

Sterol dysregulation in Smith-Lemli-Opitz syndrome causes astrocyte immune reactivity through microglia crosstalk.

Owing to the need for de novo cholesterol synthesis and cholesterol-enriched structures within the nervous system, cholesterol homeostasis is critical to neurodevelopment. Diseases caused by genetic disruption of cholesterol biosynthesis, such as Smith-Lemli-Opitz syndrome, which is caused by mutations in 7-dehydrocholesterol reductase (DHCR7), frequently result in broad neurological deficits. Although astrocytes regulate multiple neural processes ranging from cell migration to network-level communication, immunological activation of astrocytes is a hallmark pathology in many diseases. However, the impact of DHCR7 on astrocyte function and immune activation remains unknown. We demonstrate that astrocytes from Dhcr7 mutant mice display hallmark signs of reactivity, including increased expression of glial fibrillary acidic protein (GFAP) and cellular hypertrophy. Transcript analyses demonstrate extensive Dhcr7 astrocyte immune activation, hyper-responsiveness to glutamate stimulation and altered calcium flux. We further determine that the impacts of Dhcr7 are not astrocyte intrinsic but result from non-cell-autonomous effects of microglia. Our data suggest that astrocyte-microglia crosstalk likely contributes to the neurological phenotypes observed in disorders of cholesterol biosynthesis. Additionally, these data further elucidate a role for cholesterol metabolism within the astrocyte-microglia immune axis, with possible implications in other neurological diseases.

Statins for Smith-Lemli-Opitz syndrome.

BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital malformations syndrome caused by defective cholesterol biosynthesis. Affected individuals show cholesterol deficiency and accumulation of various precursor molecules, mainly 7-dehydrocholesterol and 8-dehydrocholesterol. There is currently no cure for SLOS, with cholesterol supplementation being primarily a biochemical therapy of limited evidence. However, several anecdotal reports and preclinical studies have highlighted statins as a potential therapy for SLOS. OBJECTIVES: To evaluate the effects of statins, either alone or in combination with other non-statin therapies (e.g. cholesterol, bile acid, or vitamin co-supplementation), compared to cholesterol supplementation alone or in combination with other non-statin therapies (e.g. bile acid or vitamin supplementation) on several important outcomes including overall survival, neurobehavioral features, and adverse effects in individuals with SLOS. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other databases and three trials registers on 15 February 2022, together with reference checking, citation searching and contact with study authors to identify additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs with parallel or cross-over designs, and non-randomized studies of interventions (NRSIs) including non-randomized trials, cohort studies, and controlled before-and-after studies, were eligible for inclusion in this review if they met our prespecified inclusion criteria, i.e. involved human participants with biochemically or genetically diagnosed SLOS receiving statin therapy or cholesterol supplementation, or both. DATA COLLECTION AND ANALYSIS: Two authors screened titles and abstracts and subsequently full-texts for all potentially-relevant references. Both authors independently extracted relevant data from included studies and assessed the risks of bias. We analyzed the data extracted from the included NRSIs and cohort studies separately from the data extracted from the single included RCT. We used a random-effects model to account for the inherent heterogeneity and methodological variation between these different study designs. We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included six studies (61 participants with SLOS); one RCT (N = 18), three prospective NRSIs (N = 20), and two retrospective NRSIs (N = 22). Five studies included only children, and two limited their participant inclusion by disease severity. Overall, there were nearly twice as many males as females. All six studies compared add-on statin therapy to cholesterol supplementation alone. However, the dosages, formulations, and durations of treatment were highly variable across studies. We judged the RCT as having a high risk of bias due to missing data and selective reporting. All included NRSIs had a serious or critical overall risk of bias assessed by the Risk Of Bias In Non-randomized Studies of Interventions tool (ROBINS-I). None of the included studies evaluated survival or reported quality of life (QoL). Only the included RCT formally assessed changes in the neurobehavioral manifestations of SLOS, and we are uncertain whether statin therapy improves this outcome (very low-certainty evidence). We are also uncertain whether the adverse events reported in the RCT were statin-related (very low-certainty evidence). In contrast, the adverse events reported in the NRSIs seem to be possibly due to statin therapy (risk ratio 13.00, 95% confidence interval 1.85 to 91.49; P = 0.01; low-certainty evidence), with only one of the NRSIs retrospectively mentioning changes in the irritability of two of their participants. We are uncertain whether statins affect growth based on the RCT or NRSI results (very low-certainty evidence). The RCT showed that statins may make little or no difference to plasma biomarker levels (low-certainty evidence), while we are uncertain of their effects on such parameters in the NRSIs (very low-certainty evidence). AUTHORS' CONCLUSIONS: Currently, there is no evidence on the potential effects of statin therapy in people with SLOS regarding survival or QoL, and very limited evidence on the effects on neurobehavioral manifestations. Likewise, current evidence is insufficient and of very low certainty regarding the effects of statins on growth parameters in children with SLOS and plasma or cerebrospinal fluid (CSF) levels of various disease biomarkers. Despite these limitations, current evidence seemingly suggests that statins may increase the risk of adverse reactions in individuals with SLOS receiving statins compared to those who are not. Given the insufficient evidence on potential benefits of statins in individuals with SLOS, and their potential for causing adverse reactions, anyone considering this therapy should take these findings into consideration. Future studies should address the highlighted gaps in evidence on the use of statins in individuals with SLOS by collecting prospective data on survival and performing serial standardized assessments of neurobehavioral features, QoL, anthropometric measures, and plasma and CSF biomarker levels after statin introduction. Future studies should also attempt to use consistent dosages, formulations and durations of cholesterol and statin therapy.

7-Dehydrocholesterol-derived oxysterols cause neurogenic defects in Smith-Lemli-Opitz syndrome.

Defective 3ß-hydroxysterol-Δ7 -reductase (DHCR7) in the developmental disorder, Smith-Lemli-Opitz syndrome (SLOS), results in a deficiency in cholesterol and accumulation of its precursor, 7-dehydrocholesterol (7-DHC). Here, we show that loss of DHCR7 causes accumulation of 7-DHC-derived oxysterol metabolites, premature neurogenesis from murine or human cortical neural precursors, and depletion of the cortical precursor pool, both in vitro and in vivo. We found that a major oxysterol, 3ß,5α-dihydroxycholest-7-en-6-one (DHCEO), mediates these effects by initiating crosstalk between glucocorticoid receptor (GR) and neurotrophin receptor kinase TrkB. Either loss of DHCR7 or direct exposure to DHCEO causes hyperactivation of GR and TrkB and their downstream MEK-ERK-C/EBP signaling pathway in cortical neural precursors. Moreover, direct inhibition of GR activation with an antagonist or inhibition of DHCEO accumulation with antioxidants rescues the premature neurogenesis phenotype caused by the loss of DHCR7. These results suggest that GR could be a new therapeutic target against the neurological defects observed in SLOS.

Measurement of 7-dehydrocholesterol and cholesterol in hair can be used in the diagnosis of Smith-Lemli-Opitz syndrome.

7-dehydrocholesterol (7-DHC) and cholesterol (CHOL) are biomarkers of Smith-Lemli-Opitz Syndrome (SLOS), a congenital autosomal recessive disorder characterized by elevated 7-DHC level in patients. Hair samples have been shown to have great diagnostic and research value, which has long been neglected in the SLOS field. In this study, we sought to investigate the feasibility of using hair for SLOS diagnosis. In the presence of antioxidants (2,6-ditert-butyl-4-methylphenol and triphenylphosphine), hair samples were completely pulverized and extracted by micro-pulverized extraction in alkaline solution or in n-hexane. After microwave-assisted derivatization with N,O-Bis(trimethylsilyl)trifluoroacetamide, the analytes were measured by GC-MS. We found that the limits of determination for 7-DHC and CHOL were 10 ng/mg and 8 ng/mg, respectively. In addition, good linearity was obtained in the range of 50-4000 ng/mg and 30-6000 ng/mg for 7-DHC and CHOL, respectively, which fully meets the requirement for SLOS diagnosis and related research. Finally, by applying the proposed method to real hair samples collected from 14 healthy infants and two suspected SLOS patients, we confirmed the feasibility of hair analysis as a diagnostic tool for SLOS. In conclusion, we present an optimized and validated analytical method for the simultaneous determination of two SLOS biomarkers using human hair.

Temporal changes in the brain lipidome during neurodevelopment of Smith-Lemli-Opitz syndrome mice.

Neurodevelopment is an intricately orchestrated program of cellular events that occurs with tight temporal and spatial regulation. While it is known that the development and proper functioning of the brain, which is the second most lipid rich organ behind adipose tissue, greatly rely on lipid metabolism and signaling, the temporal lipidomic changes that occur throughout the course of neurodevelopment have not been investigated. Smith-Lemli-Opitz syndrome is a metabolic disorder caused by genetic mutations in the DHCR7 gene, leading to defective 3ß-hydroxysterol-Δ7-reductase (DHCR7), the enzyme that catalyzes the last step of the Kandutsch-Russell pathway of cholesterol synthesis. Due to the close regulatory relationship between sterol and lipid homeostasis, we hypothesize that altered or dysregulated lipid metabolism beyond the primary defect of cholesterol biosynthesis is present in the pathophysiology of SLOS. Herein, we applied our HILIC-IM-MS method and LiPydomics Python package to streamline an untargeted lipidomics analysis of developing mouse brains in both wild-type and Dhcr7-KO mice, identifying lipids at Level 3 (lipid species level: lipid class/subclass and fatty acid sum composition). We compared relative lipid abundances throughout development, from embryonic day 12.5 to postnatal day 0 and determined differentially expressed brain lipids between wild-type and Dhcr7-KO mice at specific developmental time points, revealing lipid metabolic pathways that are affected in SLOS beyond the cholesterol biosynthesis pathway, such as glycerolipid, glycerophospholipid, and sphingolipid metabolism. Implications of the altered lipid metabolic pathways in SLOS pathophysiology are discussed.

A reliable tool for detecting 7-dehydrocholesterol and cholesterol in human plasma and its use in diagnosis of Smith-Lemli-Opitz syndrome.

BACKGROUND: Smith-Lemli-Opitz syndrome is a birth defect caused by the deficiency of 7-dehydrocholesterol reductase in cholesterol biosynthesis pathway, which leads to accumulation of 7-dehydrocholesterol and reduction of cholesterol in body fluids. To effectively diagnose Smith-Lemli-Opitz syndrome and monitor therapy, a reliable method for simultaneous detection of 7-dehydrocholesterol and cholesterol is needed. METHODS: In the presence of antioxidants (2,6-ditert-butyl-4-methylphenol and triphenylphosphine), 50 µL of human plasma were hydrolyzed at 70℃ for 40 min with 1 M potassium hydroxide in 90% ethanol, and then 7-dehydrocholesterol and cholesterol were extracted by 600 µL of n-hexane for three times. After microwave-assisted derivatization with 70 µL of N,O-bis(trimethylsilyl)trifluoroacetamide at 460 W for 3 min, the analytes were measured by gas chromatography-mass spectrometry. RESULTS: The limits of detection were 100 ng/mL for 7-dehydrocholesterol and 300 ng/mL for cholesterol. Good linearity was obtained in the range of 1-600 µg/mL for 7-dehydrocholesterol and 10-600 µg/mL for cholesterol, which completely covered the biochemical levels of Smith-Lemli-Opitz syndrome patients that have been reported. CONCLUSION: A time-saving and accurate gas chromatography with mass spectrometry based method was developed for the determination of 7-dehydrocholesterol and cholesterol in human plasma, which also serves as a useful tool for Smith-Lemli-Opitz syndrome diagnosis, treatment, and research.

Isolated autism is not an indication for Smith-Lemli-Opitz syndrome biochemical testing.

Several studies have demonstrated a high incidence of autistic spectrum features in individuals with Smith-Lemli-Opitz syndrome (SLOS). However, do these findings imply a converse relationship that has diagnostic utility? Is SLOS testing implicated when autism spectrum disorder (ASD) is the only clinical indication? AIM: To determine if there is any correlation with a clinical indication of ASD and a biochemical diagnosis of SLOS, based on historical test request and assay data. METHODS: Six years (2008-2013) of clinical test requests for 7-dehydrocholesterol (7-DHC) level were classified and summarised according to indication and final test result. RESULTS: From the audit period, 988 valid test results from post-natal samples were identified. In plasma/serum, mean 7-DHC level was 264.7 µmol/L (normal range < 2.0) for confirmed SLOS cases. No tests performed due to an isolated clinical indication of ASD or where no clinical information was supplied were associated with 7-DHC levels diagnostic for SLOS. CONCLUSIONS: Historical test data analysis supports the recommendation that autism/ASD as a single clinical feature is not an appropriate indication for SLOS (7-DHC) biochemical testing.

Liver Transplant and Improvements in Cholesterol Biosynthesis Defects: A Case Report of Smith-Lemli-Opitz Syndrome.

Smith-Lemli-Opitz syndrome is an autosomal recessive metabolic disease characterized by mental retardation and multiple congenital anomalies. The main pathology is the lack of the enzyme 3ß-hydroxysterol Δ7-reductase, which is the last enzymatic step in cholesterol synthesis, ending with a low cholesterol level. Cholesterol is vitally important in cell membranes and myelination of the nervous system. The cholesterol level affects many systems of the body, especially the nervous system. The cause of liver involvement in Smith-Lemli-Opitz syndrome is unclear, and many hypotheses have been suggested. Here, we present the early results of a patient with Smith-Lemli-Opitz syndrome who underwent living-donor liver transplant due to cirrhosis. As a result of liver transplant, normal cholesterol levels were shown, as well as improvements in the patient's neurodevelopment and behavior. Early liver transplant may be considered for patients with a defect of cholesterol biosynthesis, even in the absence of cirrhosis, and may be a future treatment option to prevent risks of neurologic deterioration.

[Clinical features and genetic testing of a Chinese pedigree affected with Smith-Lemli-Opitz syndrome].

OBJECTIVE: To analyze the clinical features and genetic variants of two patients from a pedigree affected with Smith-Lemli-Opitz syndrome and explore their genotype-phenotype correlation. METHODS: Clinical data and family history of the pedigree were collected. Whole exome sequencing was carried out to identify the potential variants. Suspected variants were verified by Sanger sequencing of the family members. RESULTS: The proband and her sister both presented with feeding difficulty, facial dysmorphism, seizures, and mental and speech retardation. The third child of this family presented with feeding difficulty, poor weight gain and severe malnutrition after birth. He had died of unknown cause at 6 months without genetic testing. The fourth child was a healthy boy. Genetic testing showed that both the proband and her sister have carried c.127G>T (p.Val43Phe) and c.820_825del (p.Asn274_Val275del) compound heterozygous variants of the DHCR7 gene (NM_001360.2), but the fourth child carried neither of the variants. The two variants were unreported in the literature and disease-related databases, and were not included in the 1000G and gnomAD databases. The c.820_825del variant may affect the sterol-sensitive region of the DHCR7 protein, which can lead to deletion of two amino acids at positions 247 and 275, causing truncation of the DHCR7 protein. It is speculated that this may affect the stability of protein's spatial conformation, thereby decrease the activity of the enzyme. The c.127G>T variant may affect the first transmembrane region of the protein, which is involved in the transmembrane transport of proteins. Multiple software predicted it to be harmful. Conservation analysis suggested that the three amino acids all locate in a highly conserved region of the protein. In consideration of the clinical phenotype, family history and result of genetic testing, we speculated that both patients had Smith-Lemli-Opitz syndrome due to variants of the DHCR7 gene. CONCLUSION: This pedigree has enriched the phenotypic and genotypic data of Smith-Lemli-Opitz syndrome, which clarified the genetic etiology of the patients and provided a basis for genetic counseling of this pedigree.

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 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.

Late endosomal/lysosomal accumulation of a neurotransmitter receptor in a cellular model of Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome (SLOS) is a congenital and developmental malformation syndrome associated with defective cholesterol biosynthesis. It is characterized by accumulation of 7-dehydrocholesterol (the immediate biosynthetic precursor of cholesterol in the Kandutsch-Russell pathway) and an altered cholesterol to total sterol ratio. Because SLOS is associated with neurological malfunction, exploring the function and trafficking of neuronal receptors and their interaction with membrane lipids under these conditions assume significance. In this work, we generated a cellular model of SLOS in HEK-293 cells stably expressing the human serotonin1A receptor (an important neurotransmitter G-protein coupled receptor) using AY 9944, an inhibitor for the enzyme 3ß-hydroxy-steroid-∆7 -reductase (7-DHCR). Using a quantitative flow cytometry based assay, we show that the plasma membrane population of serotonin1A receptors was considerably reduced under these conditions without any change in total cellular expression of the receptor. Interestingly, the receptors were trafficked to sterol-enriched LysoTracker positive compartments, which accumulated under these conditions. To the best of our knowledge, our results constitute one of the first reports demonstrating intracellular accumulation and misregulated traffic of a neurotransmitter GPCR in SLOS-like conditions. We believe these results assume relevance in our overall understanding of the molecular basis underlying the functional relevance of neurotransmitter receptors in SLOS.

Cerebrotendinous xanthomatosis, sitosterolemia, Smith-Lemli-Opitz syndrome and the seminal contributions of Gerald Salen, MD (1935-2020).

Cerebrotendinous xanthomatosis (CTX), sitosterolemia, and Smith-Lemli Opitz syndrome (SLOS) are rare inborn errors of metabolism. The diagnoses of CTX and sitosterolemia are often delayed for many years because of lack of physician awareness, often resulting in significant and unnecessary progression of disease. CTX may present with chronic diarrhea, juvenile onset cataracts, strikingly large xanthomas, and neurologic disease in the setting of a normal serum cholesterol, but markedly elevated serum or plasma cholestanol levels. These patients have a defect in producing the bile acid chenodoxycholate, and oral chenodeoxycholate therapy is essential for these patients in order to prevent neurologic complications. Sitosterolemia can present with xanthomas, anemia, thrombocytopenia, splenomegaly, very premature heart disease, and serum cholesterol levels that may be normal or elevated, along with marked elevations of plasma ß-sitosterol. These patients have a defect causing overabsorption of ß-sitosterol, and the treatment of choice is oral ezetimibe. SLOS presents with growth delay, intellectual disability, multiple structural anomalies, and low serum cholesterol levels, and the defect is reduced cholesterol production. Treatment consists of dietary cholesterol supplementation and oral bile acid therapy which raises serum cholesterol levels and may improve symptoms. The metabolic and genetic defects in these disorders have been defined. There is no one in our field that has contributed more to the diagnosis and treatment of these disorders than Gerald Salen, MD, who died in late 2020 at 85 years of age. He will be greatly missed by his family, friends, and colleagues from around the world.

Anthropometric characteristics of 65 Polish Smith-Lemli-Opitz patients.

Smith-Lemli-Opitz syndrome (SLOS) belongs to a group of multiple congenital anomaly/developmental delay disorders. Its primary cause lies in the defect in cholesterol biosynthesis-7-dehydrocholesterol reductase (DHCR7)-caused by pathogenic variants in the homonymous gene. Anthropometric anomalies, especially growth restriction and microcephaly, are among the most common physical manifestations of SLOS. There have been no studies analyzing the correlation between genotype, biochemical marker (7-dehydrocholesterol), and the birth and growth parameters for individuals with SLOS. This paper presents anthropometric data from the group of 65 Polish patients (aged 0.1 to 18 years) with Smith-Lemli-Opitz syndrome, with genotype and biochemical correlations for birth parameters, as well as growth in relation to molecular DHCR7 variants.

Carrier frequency and incidence estimation of Smith-Lemli-Opitz syndrome in East Asian populations by Genome Aggregation Database (gnomAD) based analysis.

BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal, recessively inherited congenital malformation syndrome characterized by multiple congenital anomalies such as microcephaly with mental defects, distinctive facial features, genital abnormalities, and 2-3 syndactyly of the toes. SLOS is caused by defective 7-dehydrocholesterol reductase, which is encoded by the DHCR7 gene. This study aimed to analyze the carrier frequency and expected incidence of SLOS in East Asians and Koreans using exome data from the Genome Aggregation Database (gnomAD) through the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guideline (2015 ACMG-AMP guideline). METHODS: We analyzed 9197 exomes for East Asian populations from gnomAD, comprising 1909 Korean, 76 Japanese, and 7212 other East Asian populations. All identified variants were classified according to the 2015 ACMG-AMP guideline. RESULTS: According to the 2015 ACMG-AMP guideline, 15 pathogenic variant/likely pathogenic variant (PV/LPV) cases were identified in 33 East Asian individuals (33/9191 = 0.4%). Among them, four PVs/LPVs were identified in 19 Korean individuals (19/1909 = 1.0%). The predicted incidence, based upon the carrier rates of PV/LPV of DHCR7 alleles, is 1 in 310,688 in East Asians and l in 40,380 in Koreans. CONCLUSIONS: This study is the first to identify carrier frequencies in East Asians and Koreans using gnomAD. It was confirmed that East Asians (0.4%) had a lower carrier frequency than did other ethnicities (1-3%) and Koreans (1.0%) had similar or lower carrier frequencies than other ethnicities. The variant spectrums of DHCR7 in East Asian and Korean populations differed greatly from those of other ethnic groups.

Voltammetry of 7-dehydrocholesterol as a new and useful tool for Smith-Lemli-Opitz syndrome diagnosis.

7-Dehydrocholesterol is an essential biomarker of Smith-Lemli-Opitz syndrome, a congenital autosomal recessive disorder. This study shows for the first time that electrochemical oxidation of 7-dehydrocholesterol can be used for its voltammetric determination. Two classes of supporting electrolytes in acetonitrile and a mixture of acetonitrile-water were used: inorganic acids known to promote structural changes of steroids and indifferent electrolytes. Oxidation of 7-dehydrocholesterol at ca +0.8 V (vs. Ag/AgNO3 in acetonitrile) in 0.1 mol L-1 NaClO4 in acetonitrile is useful for its voltammetric detection using common bare electrode materials. Detection limits for 7-dehydrocholesterol lie in the low micromolar range for all the working electrodes, including boron-doped diamond (0.4 µmol L-1) and disposable thin-film platinum electrodes (0.5 µmol L-1), which are advantageous because of the low volumes of studied solutions. After Bligh-Dyer extraction, quantification of 7-dehydrocholesterol concentration (boron-doped diamond) or concentration range (thin-film platinum) is easily attainable in artificial serum. The mere knowledge of the concentration range provides clinically valuable information, as 7-dehydrocholesterol levels are employed for SLOS diagnosis as a binary criterion (elevated, tens to hundreds µmol L-1 in symptomatic/non-elevated, typically bellow 1 µmol L-1 in healthy individuals in plasma). Moreover, it is shown that 7-dehydrocholesterol (provitamin D3) and cholecalciferol (vitamin D3) can be oxidized in 0.1 mol L-1 HClO4 in acetonitrile. Under these conditions, their voltammetric response changes dramatically, and their oxidation potential difference transiently increases from 0.08 V to 0.25 V, which should facilitate their simultaneous voltammetric determination. This work constitutes a foundation for a reliable and straightforward method for Smith-Lemli-Opitz syndrome diagnosis and monitoring 7-dehydrocholesterol's biotransformation to cholecalciferol.