Comparing Vitamin D Level Between Patients with Psoriasis and Healthy Individuals: A Systematic Review and Meta-Analysis.

BACKGROUND: Psoriasis is nowadays regarded as a systemic inflammatory disorder. Among the topicals, vitamin D derivates are often applied on the skin for their anti-inflammatory and immune-modulatory properties. Vitamin D serum levels in psoriasis (PsO) patients are still debated and an eventual depletion may offer the rational to integrate anti-psoriatic therapies with oral vitamin D. Then, we aimed to perform a systematic review and meta-analysis on the current evidence towards serum vitamin D level in PsO. METHODS: We searched in PubMed, Scopus, Web of Sciences, ScienceDirect and Science Information Database (SID) using the terms "Vitamin D" and "Psoriasis" including manuscripts in English, Italian and Persian. Duplications were excluded using EndNote software and records were screened by title, abstract and full-text. Quality assessment of studies was assessed using Newcastle Ottawa Checklist (NOS). Psoriasis odds ratio (OR) and mean serum vitamin D levels were calculated and displayed in Forest-plots. Heterogeneity indexes were evaluated using I2 and Q. Sensitivity analysis and publication biases were also considered. RESULTS: From 3006 records extracted, after removing duplicates and analyzing full texts we finally included 19 manuscripts involving a total of 1387 PsO cases and 6939 controls. PsO patients exhibited a substantial odds ratio (3.07, 95% CI: 1.56-6.04) for lower serum vitamin D levels compared to the control group. Standardized Mean Difference (SMD) of vitamin D in PsO versus controls was -0.92 (-1.33 to -0.51). CONCLUSION: Psoriatic patients displayed higher risk to have a vitamin D deficiency. Interventional studies to verify the preventive value are mandatory.

Vitamin D in the Prevention and Treatment of Oral Cancer: A Scoping Review.

Introduction: Oral cancer is a serious health problem with an increasing incidence worldwide. Researchers have studied the potential anti-cancerous action of vitamin D and its association with several cancers including oral cancer. The purpose of this scoping review is to synthesize the existing literature on the role of vitamin D on oral cancer. Methods: A scoping review of the literature was conducted using the framework developed by Arkey and O'Malley and the PRISMA-ScR guidelines. Nine databases were searched for peer-reviewed human studies published in English that either investigated the association of vitamin D with, or its impact on either the prevention or treatment of oral cancer. The authors then extracted data using a predefined form to summarize information about article type, study design, participant characteristics, interventions, and outcomes. Results: Fifteen articles met the review criteria. Among the 15 studies, 11 were case-control, 3 were cohort studies, and 1 was a clinical trial. In four studies, the evidence supported a preventive action of vitamin D against oral cancer and a reduction in the negative side effects associated with chemo- and radiotherapy. Several studies that focused on genetic polymorphisms and the expression of the 1,25 dihydroxyvitamin D3 receptor (VDR) suggested significant associations with vitamin D and increased oral cancer risk and worse survival rates. In contrast, two studies did not reveal a strong association between vitamin D and oral cancer. Conclusions: The current evidence suggests an association between vitamin D deficiency and an increased risk of oral cancer. VDR gene polymorphisms might also be a part of future preventive and therapeutic strategies against oral cancer. Carefully designed studies are required to explore and define what role, if any, vitamin D might play in the prevention and treatment of oral cancer.

Association of Maternal Gestational Vitamin D Supplementation with Respiratory Health of Young Children.

This study aimed to evaluate the association between maternal gestational Vitamin D3 supplementation and early respiratory health in offspring. This was a population-based record-linkage study which used data from the French National Health Database System. Maternal Vitamin D3 supplementation consisted of a single high oral dose of cholecalciferol, (100,000 IU) from the seventh month of pregnancy, according to national guidelines. In total, 125,756 term-born singleton children were included, of which 37% had respiratory illness defined as hospital admission due to respiratory causes or inhalation treatment up to 24 months of age. Infants prenatally exposed to maternal Vitamin D3 supplementation (n = 54,596) were more likely to have a longer gestational age (GA) at birth (GA 36-38 weeks, 22% vs. 20%, p < 0.001 in exposed vs. non-exposed infants, respectively). After adjusting for the main risk factors (maternal age, socioeconomic level, mode of delivery, obstetrical and neonatal pathology, birth weight appropriateness, sex, and birth season), the risk of RD was found to be 3% lower than their counterparts (aOR [IC 95%], 0.97 [0.95-0.99], p = 0.01). In conclusion, this study provides evidence for the association between maternal gestational Vitamin D3 supplementation and improved early respiratory outcomes in young children.

Vitamin D deficiency in melanoma patients is associated with worse overall survival: a retrospective cohort study.

Recent interest has emerged in the protective role of vitamin D in melanoma survival and is the subject of multiple studies with heterogeneous results. Here, we present a retrospective cohort study of 264 patients with invasive melanoma from a tertiary university hospital. The aim of the study was to analyze the relationship between vitamin D levels and prognosis of melanoma patients. We found that lower vitamin D levels are independently associated with worse overall survival in melanoma patients in concordance with previous studies on other populations. Vitamin D deficiency could play a survival role in melanoma patients,. Future prospective studies are needed to investigate the effect of vitamin D supplementation on melanoma outcomes.

Serum Vitamin D Level and Efficacy of Vitamin D Supplementation in Children with Atopic Dermatitis: A Systematic Review and Meta-analysis.

Background: The relationship between vitamin D and atopic dermatitis (AD) is controversial. This meta-analysis is aimed at exploring vitamin D level and its deficiency in pediatric AD and at evaluating the efficacy of vitamin D supplementation. Methods: PubMed, Medline, Embase, Ovid, Cochrane Library, ISI Web of Science, and ClinicalTrials were searched. Binary variables and continuous variables were measured by odds ratio (OR) and mean difference (MD) with 95% confidence intervals, respectively. The modified Jadad scale, Newcastle-Ottawa Scale (NOS), and Cochrane's bias risk tools were used to evaluate study quality and the risk of bias of eligible studies, respectively. Results: A total of 22 literature were included in the analysis. Serum 25 (OH) D level in pediatric AD patients was significantly lower than that of the control group with a combined MD value of -8.18 (95% CI: -13.15, -3.22). Patients with AD were more prone to develop vitamin D deficiency with a combined OR value of 2.17 (95% CI: 1.15, 4.11). According to the score of SCORAD, the level of serum 25 (OH) D level in patients with severe AD was significantly lower than that in patients with mild AD (combined MD = 9.23, 95% CI: 6.92, 11.55). Both self-control studies and randomized controlled trials showed improved SCORAD score and EASI score after vitamin D supplementation. Conclusion: This meta-analysis showed lower serum 25 (OH) D level and increased risk of vitamin D deficiency in pediatric AD patients as compared with healthy controls. The serum 25 (OH) D level in severe AD patients was significantly lower than that in the mild AD patients. The SCORAD and EASI score improved after vitamin D supplementation, suggesting its beneficial effect to AD patients. At the same time, more homogeneous studies are needed to reduce confounding factors and further evaluate the impact of vitamin D treatment on the outcome of AD patients.

A Phase II Multicenter Trial on High-Dose Vitamin D Supplementation for the Correction of Vitamin D Insufficiency in Patients with Breast Cancer Receiving Adjuvant Chemotherapy.

Breast cancer (BC) treatments induce vitamin D (VD) insufficiency and bone metabolism changes, resulting in osteoporosis and skeletal morbidity risk. We report the results of a bicentric phase II trial (ClinicalTrials.gov Identifier: NCT04091178) on the safety and efficacy of high-dose oral VD supplementation for VD deficiency correction in 44 patients with early BC treated with adjuvant chemotherapies. Patients received one dose of 100,000 IU 25-OH VD every 3 weeks from day 1 of cycle 1 to day 1 of cycle 5. The primary endpoint was the percentage of patients achieving serum 25-OH VD concentration normalization on day 1 of cycle 6 (D1C6). Secondary endpoints were safety, VD and calcium parameters at baseline and during chemotherapy, and identification of predictive biomarkers of VD normalization on D1C6. On D1C6, 21 patients (47.7%, 95% CI: 33.0-62.8) achieved VD normalization. No VD-related clinical toxicity was reported. However, 13 patients (29.5%) presented asymptomatic grade 1 hypercalciuria, leading to interruption of the high-dose oral VD supplementation in 10, followed by a rapid reduction in serum VD concentration. No baseline clinical factor was predictive of VD normalization on D1C6. This high-dose VD supplementation appears safe and efficient in patients with early BC receiving adjuvant chemotherapy.

Vitamin D Assessment Over 48 Weeks in Treatment-Naive HIV Individuals Starting Lopinavir/Ritonavir Monotherapy.

BACKGROUND: Vitamin D deficiency is common in HIV population and has been associated with increased comorbidity risk and poor immunologic status. OBJECTIVE: To evaluate the effect of protease inhibitor lopinavir/ritonavir monotherapy on changes in serum 25-hydroxyvitamin D [25(OH)D] over 48 weeks. METHODS: Thirty-four treatment-naïve HIV individuals initiating lopinavir/ritonavir monotherapy and receiving clinical care from private practice in Houston, Texas, were included. Serum 25-hydroxyvitamin D levels from stored plasma samples collected from IMANI-2 pilot study at both baseline and 48 weeks were analyzed using LC-MS assays. Mean 25(OH)D at baseline and 48 weeks were compared using paired t-tests. Linear regression analysis was used to evaluate factors associated with changes in 25(OH)D. Logistic regression analyses were used to determine the effect of vitamin D status and covariates on CD4 cell count recovery. RESULTS: Mean 25(OH)D was significantly higher at 48 weeks (26.3 ng/mL (SD + 14.9); p=0.0003) compared to baseline (19.8 ng/mL (SD +12.1), with fewer individuals having vitamin D deficiency (41.2%) and severe deficiency (11.8%). Both body mass index and baseline CD4 cell count were significant independent covariates associated with 25(OH)D changes over 48 weeks. Baseline vitamin D status did not affect CD4 cell count recovery. However, in a 24-week multivariate analysis, current tobacco use was significantly associated with a decreased odds of CD4 cell count recovery (AOR 0.106, 95% CI 0.018-0.606; p=0.012). CONCLUSION: Individuals treated with lopinavir/ritonavir monotherapy had significantly higher 25(OH)D after 48 weeks. Current tobacco users had significantly diminished CD4 cell count recovery after starting treatment, warranting further clinical investigation.

Symptomatic hypocalcemia following a single dose of zoledronic acid in a patient with bone metastases secondary to breast cancer.

INTRODUCTION: The use of bisphosphonates is increasing, for treatment of hypercalcemia and pain in cancer, and post-menopausal osteoporosis and also to decrease the risk of skeletal morbidity in multiple myeloma and metastatic breast cancer. CASE REPORT: A single dose of zoledronic acid was administered for hypercalcemia in a 54-year-old woman breast cancer patient with extensive bone metastasis. After the first dose, the patient developed symptomatic hypocalcemia.Management and outcome: Simultaneous hypocalcemia, hypophosphatemia, and vitamin D deficiency were detected in the patient. In the symptomatic process, intravenous, then oral replacement was performed. DISCUSSION: There is a need for taking precautionary measures such as vitamin D, serum phosphorus and, calcium monitoring and supplementation to prevent life-threatening complications, such as symptomatic hypocalcemia, especially in populations with vitamin D deficiency like ours.

Anticonvulsivantes y su efecto en el metabolismo de la vitamina D: revisión del tema, a propósito de un caso / Anticonvulsants and their effect on the metabolism of vitamin D: literature review with case report

La epilepsia es una enfermedad neurológica frecuente que afecta a cerca de 50.000 millones de personas en el mundo. En Chile, la prevalencia estimada es de 10.8 a 17 por 1.000 habitantes. La primera opción para su tratamiento son los fármacos antiepilépticos (FAE) los cuales logran un aceptable control de enfermedad en la mayoría de los casos, sin embargo, tienen la potencialidad de desencadenar una serie de efectos adversos destacando entre ellos el desarrollo de hipocalcemia (HC) secundaria a hipovitaminosis D (HD), alteración que por lo general es leve y asintomática. Presentamos el caso de una mujer perimenopausica con antecedente de epilepsia en tratamiento con anticonvulsivante que desarrolla hipocalcemia severa. Además revisamos los mecanismos descritos a través de los cuales los FAE afectan el metabolismo de esta vitamina.

Epilepsy is a common neurological disease that affects about 50,000 million people in the world. The estimated prevalence is 10.8 to 17 per 1.000 inhabitants in Chile. The first option for its treatment are antiepileptic drugs (AEDs) which achieve an acceptable control of the disease in most cases, however, they have the potential to trigger a series of adverse effects (AE) highlighting among them the development of hypocalcemia (HC) secondary to hypovitaminosis D (HD), an alteration that is generally mild and asymptomatic. We present the case of a perimenopausal woman with a history of epilepsy under treatment with an anticonvulsant who develops severe hypocalcemia. We also review the mechanisms described through which AEDs affect the metabolism of this vitamin.

Effect of Chronic Vitamin D Deficiency on the Development and Severity of DSS-Induced Colon Cancer in Smad3-/- Mice.

Both human epidemiologic data and animal studies suggest that low serum vitamin D increases the risk of inflammatory bowel disease (IBD) and consequently IBD-associated colorectal cancer. We tested the hypothesis that vitamin D deficiency increases the risk for colitis-associated colon cancer (CAC) by using an established CAC mouse model, 129-Smad3tm1Par/J (Smad3-/-) mice, which have defective transforming growth factor ß-signaling and develop colitis and CAC after the administration of dextran sodium sulfate (DSS). After determining a dietary regimen that induced chronic vitamin D deficiency in Smad3-/- mice, we assessed the effects of vitamin D deficiency on CAC. Decreasing dietary vitamin D from 1 IU/g diet (control diet) to 0.2 IU /g diet did not decrease serum 25-hydroxyvitamin D (25(OH)D) levels in Smad3-/- mice. A diet devoid of vitamin D (< 0.02 IU/g diet [no added vitamin D]; vitamin D-null) significantly decreased serum 25(OH)D levels in mice after 2 wk (null compared with control diet: 8.4 mg/mL compared with 12.2 ng/mL) and further decreased serum levels to below the detection limit after 9 wk but did not affect weight gain, serum calcium levels, bone histology, or bone mineral density. In light of these results, Smad3-/- mice were fed a vitamin D-null diet and given DSS to induce colitis. Unexpectedly, DSS-treated Smad3-/- mice fed a vitamin D-null diet had improved survival, decreased colon tumor incidence (8% compared with 36%), and reduced the incidence and severity of colonic dysplasia compared with mice fed the control diet. These effects correlated with increased epithelial cell proliferation and repair early in the disease, perhaps reducing the likelihood of developing chronic colitis and progression to cancer. Our results indicate that vitamin D deficiency is beneficial in some cases of CAC, possibly by promoting intestinal healing.

Association between standardized vitamin 25(OH)D and dyslipidemia: a community-based study in Riyadh, Saudi Arabia.

BACKGROUND: Vitamin D deficiency associated with dyslipidemia can contribute towards cardiovascular diseases. Previous studies have found that Saudi Arabia has a high burden of vitamin D deficiency and cardiovascular disease risk factors. We aimed to explore the relationship between vitamin D deficiency and dyslipidemia, including total cholesterol, low-density lipids, high-density lipids (HDL), and triglycerides (TG) in apparently healthy Saudi male and female participants aged 30-75 years. METHODS: A cross-sectional study was conducted on 1717 apparently healthy Saudi participants from 18 primary health care centers in Riyadh. Data collectors conducted the interviews, took anthropometric measurements, and collected the blood samples. Serum 25-hydroxyvitamin vitamin D (25(OH)D) levels were measured using an electrochemiluminescence assay method. Lipid panel was measured by a fully automated analyzer using enzymatic methods. RESULTS: Multivariable logistic regression analysis revealed that the adjusted odds ratio (ORA) of low level of HDL cholesterol in association with 25(OH)D deficiency was 2.1 times higher in males (ORA = 2.1; 95% CI = 1.1, 3.9) and 1.3 times higher in females (ORA = 1.3; 95% CI = 0.9, 1.9). A significant excess odds ratio of high levels of TG in association with 25(OH) D deficiency was observed in females (ORA = 3.0; 95% CI = 1.1, 7.9) but not in males. CONCLUSION: Vitamin D deficiency is highly prevalent in Saudi Arabia. Low levels of HDL cholesterol in men and high TG levels in women are associated with vitamin D deficiency. The results emphasize the importance of treating vitamin D deficiency in the general population.

Valproate decreases vitamin D levels in pediatric patients with epilepsy.

PURPOSE: To compare Vitamin D (Vit D) levels in children with epilepsy on valproate monotherapy with healthy controls. METHODS: A meta-analysis performed on articles identified from PubMed and Web of Science online databases evaluated using National Institute of Health National Heart, Lung, and Blood Institute Study Quality Assessment Tools. Subgroup analyses and publication bias assessments were also performed. RESULTS: Eleven publications were eligible based on inclusion/exclusion criteria for the meta-analysis. Results noted a decrease in the mean Vit D level in children with epilepsy on valproate monotherapy compared with healthy children with a Standard Mean Difference = -0.313 [-0.457, -0.169]. Cumulative meta-analysis showed progressive negative effect of valproate therapy on Vit D levels across time. Other antiepileptic medications caused a similar effect on Vit D status. There was no evidence of publication bias in the analyses. Type of study design and country of origin introduced heterogeneities into the meta-analyses. CONCLUSION: This meta-analysis provides evidence that long-term therapy with valproate causes a decrease in Vit D levels in children. Therefore, in children with a seizure disorder on long-term valproate therapy, 25-OH-Vit D levels should be monitored and appropriate supplementation implemented if levels are deficient.

Vitamin D supplementation and bone markers in ambulatory children on long-term valproic acid therapy. A prospective interventional study.

PURPOSE: Our aim was to investigate any adverse effects of long-term valproic acid (VPA) therapy on bone biochemical markers in ambulatory children and adolescents with epilepsy, and the possible benefits of vitamin D supplementation on the same markers. METHODS: In this single center, the prospective interventional study levels of 25-hydroxyvitamin D (25OHD) and the bone turnover indices of Crosslaps (CTX), total alkaline phosphatase (tALP), osteoprotegerin (OPG), and the receptor activator for nuclear factor kB (RANK) ligand (sRANKL) were assessed before and after one year of vitamin D intake (400 IU/d) and were compared with those of clinically healthy controls. Fifty-four ambulatory children with mean (±standard deviation [SD]) age 9.0 ±â€¯4.5 yrs on VPA (200-1200 mg/d) long-term monotherapy (mean: 3.2 ±â€¯2.6 yrs) were studied, before and after a year's vitamin D intake (400 IU/d). RESULTS: Nearly half of the cases were vitamin D insufficient/deficient with mean levels 23.1 ±â€¯12.8 vs 31.8 ±â€¯16.2 ng/mL of controls (p = 0.004) and after the year of vitamin D intake increased to 43.2 ±â€¯21.7 ng/mL (p < 0.0001). In parallel, serum CTX and tALP had a decreasing trend approaching control levels but OPG and sRANKL did not change and were not different from controls. However, after vitamin D intake, a positive correlation was seen between 25OHD and OPG but not before. CONCLUSIONS: The findings imply a higher bone turnover in the young patients on long-term VPA therapy that decreased after vitamin D intake.

Gender, hyperandrogenism and vitamin D deficiency related functional and morphological alterations of rat cerebral arteries.

Hyperandrogenism is a risk factor of cerebrovascular diseases as androgens can alter markedly the regulation of cerebrovascular tone. We examined the combined impact of androgen excess and vitamin D deficiency (VDD), a common co-morbidity in hyperandrogenic disorders, on remodeling and testosterone-induced vascular responses of anterior cerebral arteries (ACA) in order to evaluate the interplay between androgens and VDD in the cerebral vasculature. Male and female Wistar rats were either fed with vitamin D deficient or vitamin D supplemented diet. Half of the female animals from both groups received transdermal testosterone treatment. After 8 weeks, vessel lumen, wall thickness and testosterone-induced vascular tone of isolated ACA were determined using pressure microangiometry and histological examination. Androgen receptor protein expression in the wall of cerebral arteries was examined using immunohistochemistry. In female rats only combined VDD and testosterone treatment decreased the lumen and increased the wall thickness of ACA. In males, however VDD by itself was able to decrease the lumen and increase the wall thickness. Vascular reactivity showed similar alterations: in females, testosterone constricted the ACA only after combined VDD and hyperandrogenism, whereas in males VDD resulted in increased testosterone-induced contractions in spite of decreased androgen receptor expression. In conclusion, a marked interplay between hyperandrogenism and VDD results in inward remodeling and enhanced testosterone-induced constrictions of cerebral arteries, which might compromise the cerebral circulation and thus, increase the risk of stroke in the long term. In addition, the early cerebrovascular manifestation of VDD appears to require androgen excess and thus, depends on gender.

Effect of high dose vitamin d supplementation on vitamin d nutrition status of pre-pubertal children on anti-epileptic drugs - A randomized controlled trial.

BACKGROUND AND AIMS: Patients on long term anti-epileptic drug therapy are prone for Vitamin D deficiency for a myriad of reasons. The aim of this research was to study the effect of high dose vitamin D supplementation on vitamin D nutrition status of children newly started on anti-epileptic drug therapy. MATERIALS: This randomized controlled trial was conducted in a tertiary care Children's Hospital at New Delhi from November 2011 to March 2013. Eighty three children in the age group 5-10 years newly started on anti-epileptic drugs (AED) were randomized into two groups; group A - the intervention group, to whom 60,000 IU vitamin D3 was given orally/month under direct supervision along with AED for a period of 6 months, and group B- the control group, to whom AED without vitamin D3 was given. Serum 25(OH)D, ionized calcium (iCa), total calcium (tCa), inorganic phosphate (iP), alkaline phosphatase (ALP) and parathyroid hormone (PTH) levels were assayed at baseline and at the end of 6 months and were compared within and between the two groups. RESULTS: The mean 25(OH)D in Group A was maintained at 6 months follow up [ 26 ng/ml, 95% CI 20-34 ng/ml] compared to baseline [25 ng/ml, 95% CI -19 to 33 ng/ml] [ p = 0.83]. In group B, there was a significant decrease in 25(OH)D levels at 6 months [13 ng/ml (95% CI 9 ng/ml-17 ng/ml)] compared to baseline [18 ng/ml (95% CI 13-24 ng/ml)] [p = 0.01]. At 6 months, mean serum 25(OH)D was significantly higher in group A as compared to group B (p = 0.005). CONCLUSION: To conclude, oral administration of 60,000 IU vitamin D3/month is sufficient to maintain serum 25(OH)D level and prevent development of vitamin D deficiency in children newly started on AED over a period of 6 months. Non supplementation leads to the lowering of serum 25(OH)D in these children. TRIAL REGISTRATION NUMBER: CTRI/2017/08/009234.

Air pollution, environmental chemicals, and smoking may trigger vitamin D deficiency: Evidence and potential mechanisms.

Beyond vitamin D (VD) effect on bone homeostasis, numerous physiological functions in human health have been described for this versatile prohormone. In 2016, 95% of the world's population lived in areas where annual mean ambient particulate matter (<2.5 µm) levels exceeded the World Health Organization guideline value (Shaddick et al., 2018). On the other hand, industries disperse thousands of chemicals continually into the environment. Further, considerable fraction of populations are exposed to tobacco smoke. All of these may disrupt biochemical pathways and cause detrimental consequences, such as VD deficiency (VDD). In spite of the remarkable number of studies conducted on the role of some of the above mentioned exposures on VDD, the literature suffers from two main shortcomings: (1) an overview of the impacts of environmental exposures on the levels of main VD metabolites, and (2) credible engaged mechanisms in VDD because of those exposures. To summarize explanations for these unclear topics, we conducted the present review, using relevant keywords in the PubMed database, to investigate the adverse effects of exposure to air pollution, some environmental chemicals, and smoking on the VD metabolism, and incorporate relevant potential pathways disrupting VD endocrine system (VDES) leading to VDD. Air pollution may lead to the reduction of VD cutaneous production either directly by blocking ultraviolet B photons or indirectly by decreasing outdoor activity. Heavy metals may reduce VD serum levels by increasing renal tubular dysfunction, as well as downregulating the transcription of cytochrome P450 mixed-function oxidases (CYPs). Endocrine-disrupting chemicals (EDCs) may inhibit the activity and expression of CYPs, and indirectly cause VDD through weight gain and dysregulation of thyroid hormone, parathyroid hormone, and calcium homeostasis. Smoking through several pathways decreases serum 25(OH)D and 1,25(OH)2D levels, VD intake from diet, and the cutaneous production of VD through skin aging. In summary, disturbance in the cutaneous production of cholecalciferol, decreased intestinal intake of VD, the modulation of genes involved in VD homeostasis, and decreased local production of calcitriol in target tissues are the most likely mechanisms that involve in decreasing the serum VD levels.

Familial congenital choanal atresia with GATA3 associated hypoparathyroidism-deafness-renal dysplasia syndrome unidentified on auditory brainstem response.

Hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is a rare autosomal dominant disorder primarily caused by GATA3 haploinsufficiency and is challenging to diagnose in early childhood. We report a Japanese family with HDR syndrome and congenital choanal atresia. The 6-year-old female proband was diagnosed with epilepsy at the age of three. Under carbamazepine monotherapy, the patient presented hypoparathyroidism accompanied by severe hypocalcemia. Subsequently, renal ultrasound analysis revealed bilateral multicystic dysplastic kidneys. Because she had difficulty hearing, we sequenced GATA3 and determined that she had a c.708_709insC (p.Ser237Glnfs*66) allelic variant in exon 3. As a result, we found a family of this disease. Each family member, including her grandfather, mother, and two siblings, had HDR syndrome of varying clinical penetrance. We found a craniofacial anomaly, congenital choanal atresia, which was inherited as an autosomal dominant trait. Hypocalcemia coupled with vitamin D deficiency, triggered by carbamazepine treatment, ultimately revealed the proband's childhood- onset HDR syndrome. Pure-tone audiometry revealed different severities of deafness as well as the progression of sensory hearing loss. However, auditory brainstem response for hearing screening is probably insufficient for ascertaining HDR syndrome in the early stages of life. We presented new clinical clues to diagnose the HDR syndrome.