The clinical presentation, treatment, and follow-up of two boys with type 1 Dent disease who exhibited a Bartter-like phenotype were retropectively analysed. The related literature of pediatric patients with type 1 Dent disease who had hypokalemia and metabolic alkalosis was screened through databases such as PubMed, CNKI, and Wanfang until February 1, 2024, and common features among these patients were summarized through literature review. A total of 7 literatures were included, and 9 children were included in the analysis. All patients were male, presenting with significant low molecular weight proteinuria and hypercalciuria. Other prominent characteristic phenotypes included short stature (7/8), hypophosphatemia (8/9), and rickets (6/8). Seven previously reported patients had missense or nonsense mutations, while 2 patients in this study carried possible pathogenic mutations in the CLCN5 gene, c.315+2T>A (p.?) and c.584dupT (p.I196Yfs*6), respectively. Five patients were able to maintain blood potassium levels around 3 mmol/L with oral potassium chloride solution combined with non-steroidal anti-inflammatory drugs (ibuprofen or indomethacin). The follow-up showed that 2 patients developed chronic kidney disease stage 4 and stage 3 at the age of 13 and 21 years, respectively. The phenotypic overlap between Dent disease and Batter syndrome is considerable,with the distinguishing feature being the presence of significant low molecular weight proteinuria. Patients with type 1 Dent disease presenting with the Bartter-like phenotype have a high prevalence of short stature, hypophosphatemia, and rickets. Non-steroidal anti-inflammatory drugs can be used to correct hypokalemia in patients under periodic renal function assessment.
回顾性分析2例以巴特样表型起病的登特病1型男性患儿的临床表现、治疗及随访。检索PubMed、知网、万方等数据库，从建库至2024年2月1日，筛选低钾血症合并代谢性碱中毒的登特病1型患儿相关文献，通过文献复习总结此病患儿的临床特征。纳入7篇文献，9例患儿纳入分析。患者均为男性，均有大量低分子蛋白尿和高钙尿症，其他突出的特征性表型包括身材矮小（7/8）、低磷血症（8/9）及佝偻病（6/8）。已报道的7例患者为CLCN5基因错义或无义突变，本研究报道的2例患者分别携带CLCN5基因可能致病性突变：c.315+2T>A（p.？）及c.584dupT（p.I196Yfs*6）。5例患者经氯化钾口服液联合非甾体类抗炎药（布洛芬或吲哚美辛）能维持血钾水平在3 mmol/L左右。随访显示有2例患者分别在13和21岁时出现慢性肾脏病4期和3期。登特病与巴特综合征表型重合度高，鉴别点在于是否存在大量低分子蛋白尿。以巴特样表型起病的登特病1型患者身材矮小、低磷血症及佝偻病的发生率高。在定期检测肾功能的情况下，非甾体抗炎药可用于纠正患者的低钾血症。.

OBJECTIVE: The objective of this systematic review was to determine a minimum serum 25-hydroxyvitamin D (25OHD) threshold based on the risk of having rickets in young children. This work was commissioned by the WHO and FAO within the framework of the update of the vitamin D requirements for children 0-3 years old.
METHODS: A systematic search of Embase was conducted to identify studies involving children below  4 years of age with serum 25OHD levels and radiologically confirmed rickets, without any restriction related to the geographical location or language. Study-level and individual participant data (IPD)-level random effects multi-level meta-analyses were conducted. The odds, sensitivity and specificity for rickets at different serum 25OHD thresholds were calculated for all children as well as for children with adequate calcium intakes only.
RESULTS: A total of 120 studies with 5412 participants were included. At the study-level, children with rickets had a mean serum 25OHD of 23 nmol/L (95% CI 19-27). At the IPD level, children with rickets had a median and mean serum 25OHD of 23 and 29 nmol/L, respectively. More than half (55%) of the children with rickets had serum 25OHD below 25 nmol/L, 62% below 30 nmol/L, and 79% below 40 nmol/L. Analysis of odds, sensitivities and specificities for nutritional rickets at different serum 25OHD thresholds suggested a minimal risk threshold of around 28 nmol/L for children with adequate calcium intakes and 40 nmol/L for children with low calcium intakes.
CONCLUSIONS: This systematic review and IPD meta-analysis suggests that from a public health perspective and to inform the development of dietary requirements for vitamin D, a minimum serum 25OHD threshold of around 28 nmol/L and above would represent a low risk of nutritional rickets for the majority of children with an adequate calcium intake.

Vitamin D-dependent rickets type 1 (VDDRIA) is an autosomal recessive disorder caused by mutations in the Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1) gene, which encodes for the enzyme 1 alpha-hydroxylase. We report a known case of VDDRIA with hypotonia, growth and developmental disorders and discuss about the mutation and its management.

Although vitamin D deficiency resulting from insufficient sunlight exposure or inadequate dietary vitamin D intake is the most common cause of rickets, mutations in genes involved in vitamin D metabolism can cause genetic forms of rickets termed Vitamin D-Dependent Rickets (VDDR). In 2018, Roizen et al. described a new type of VDDR, named VDDR3, caused by a recurrent missense mutation in the CYP3A4 gene that leads to accelerated inactivation of vitamin D metabolites. Here, we describe the third case of VDDR3 due to the same CYP3A4 mutation in a 2-year-old boy with bone deformities associated with poor growth. As in the previously reported cases, this patient had no family history of rickets. Serial measurements of vitamin D metabolites after a single 150,000 IU dose of cholecalciferol demonstrated an accelerated inactivation of 25(OH)D and 1,25(OH)2D. Significant improvement in growth velocity and healing of bone deformities were achieved after a short period of treatment with 10.000 IU of cholecalciferol daily, showing the importance of early recognition and prompt precision therapy of this condition.

BACKGROUND: Craniosynostosis (CSS) is the premature fusion of calvarial sutures associated with identified genetic mutations or secondary to alterations in intracranial pressure, brain, or bone growth patterns. Of the metabolic etiologies implicated in CSS, X-linked hypophosphatemic rickets (XLHR) is the most common, with dysfunctional bone mineralization leading to progressive hyperostosis and delayed synostosis. There is a paucity of literature discussing the unique surgical considerations for XLHR-related CSS.
METHODS: A 26-month-old male with XLHR-related sagittal CSS underwent cranial vault remodeling (CVR). Surgery was complicated by the presence of diploic hypertrophy with significant intraoperative estimated blood loss (EBL). EBL greatly exceeded reference ranges for CVR in all-cause CSS. As a result, the surgical goals were modified and the complete planned procedure aborted. Subsequent review of preoperative imaging revealed multiple fine vascular lacunae within the bone. A systematic literature review was conducted to identify reported complications relating to surgical intervention for rickets-associated CSS.
CONCLUSIONS: Future considerations for patients with XLHR-related CSS should emphasize awareness of metabolic risk factors with associated complications, and the need for selection of approach and operative management techniques to avoid EBL. Further research is required to elucidate underlying mechanisms and determine whether the encountered phenomenon is characteristic across this patient population and potentially minimized by preoperative medical therapy.

Long considered an inert supporting framework, bone studies went neglected until the 17th century when they began as descriptive microscopic studies of structure which over time progressed into that of chemistry and physiology. It was in the mid-19th century that studies evolved into an inquisitive discipline which matured into the experimental investigation of bone in health and disease in the 20th century, and ultimately that of molecular studies now deciphering the genetic language of bone biology. These fundamental studies were catalyzed by increasing clinical interest in bone disease. The first bone disease to be identified was rickets in 1645. Its subsequent connection to albuminuric patients reported in 1883 later became renal osteodystrophy in 1942, launching studies that elucidated the functions of vitamin D and parathyroid hormone and their role in the altered calcium and phosphate metabolism of the disease. Studies in osteoporosis and renal osteodystrophy have driven most recent progress benefitting from technological advances in imaging and the precision of evaluating bone turnover, mineralization, and volume. This review exposes the progress of bone biology from a passive support structure to a dynamically regulated organ with vital homeostatic functions whose understanding has undergone more revisions and paradigm shifts than that of any other organ.

Vitamin D has several roles in the immune system besides its effects on bone metabolism. Acute respiratory infections are common infections in children. Severe lower respiratory tract infections (LRTIs) even cause death in children, especially in those less than five years of age. Our study aims to examine whether children with vitamin D deficiency are susceptible to respiratory infections and to study the association between vitamin D deficiency and the severity of respiratory infections. We comprehensively searched research articles in PubMed, ScienceDirect, and Cochrane library databases. The main keywords were vitamin D deficiency, respiratory infections, and children. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to conduct this systematic review. The initial search showed 16,120 papers. A meticulous screening of research articles using the eligibility criteria and quality appraisal tools was done. Finally, 10 research articles qualified for this systematic review, including eight case-control studies, one randomized controlled trial (RCT), and one cohort study. Seven of 10 research studies reviewed found that children with low vitamin D levels are susceptible to respiratory infections. Five studies discussed the severity of respiratory infections and low vitamin D levels. This systematic review concluded that children with low vitamin D levels are prone to developing respiratory infections. But we could not find a conclusive association between the severity of respiratory infections and low vitamin D levels.

Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) is a rare form of hereditary rickets, which is characterized by defective bone mineralization and renal phosphate wasting due to a loss-of-function variant in the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene. Although pathogenic variant of ENPP1 has been known to manifest other phenotypes including arterial calcification, hearing loss, ossification of posterior longitudinal ligament, or pseudoxanthoma elasticum, there have been few reports including systematic examination in individuals diagnosed with ARHR2 to date. Herein, we report a case of ARHR2 with a bi-allelic pathogenic variant of ENPP1, in which the patient presented with gait abnormalities with severe genu varum at 26 months of age. Targeted gene panel sequencing was performed to investigate the genetic cause of rickets, and a homozygous nonsense variant in ENPP1, c.783C>G (p.Tyr261*), was identified. The patient was treated with oral phosphate and active vitamin D supplements and underwent corrective osteotomy for varus deformity. His phenotype was limited to rickets. A periodic systematic evaluation is needed to identify any comorbidities in ARHR2 patients since ENPP1 variants may present phenotypes other than rickets and symptoms may evolve or change over time.

Vitamin D deficiency and insufficiency are highly prevalent conditions worldwide due to several factors, including poor sun exposure. Shift workers may be exposed to the risk of hypovitaminosis D due to fewer opportunities for sunlight exposure compared to day workers. A systematic review of the PubMed, SCOPUS, and EMBASE databases was conducted according to the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) statement to investigate the effect of shift work on vitamin D levels. Mean differences (MD) and 95% confidence intervals (CI) of serum 25-OH-D levels in shift workers and non-shift workers were calculated. A total of 13 cross-sectional studies were included in the meta-analysis. We found significantly lower levels of serum 25-OH-D in shift workers compared with non-shift workers (MD: −1.85, 95% CI [−2.49 to −1.21]). Heterogeneity among included studies was high (I2 = 89%, p < 0.0001), and neither subgroup analysis nor meta-regression were able to identify specific sources of the heterogeneity that may be related to the different characteristics of shift work among studies. The monitoring of serum vitamin D levels and prompt correction of any deficiencies should be considered in shift workers. Notably, since a large part of the observations are derived from Koreans, larger epidemiological studies are needed in other populations.

Hypophosphatemic rickets can cause a variety of bone and joint symptoms, one of its rare presentations is sacroiliac joint involvement, which may be mistaken for inflammatory spondylitis. Here, we report the case of a 31-year-old African American woman who presented with a two-year history of lower back pain and morning stiffness, initially suspected to be due to inflammatory spondyloarthritis. Laboratory tests revealed negative inflammatory markers, normal serum calcium, vitamin D3, and parathyroid hormone levels; however, the alkaline phosphatase levels were elevated and serum phosphorus level was low. Magnetic resonance imaging (MRI) of the lumbosacral spine revealed mild widening of the sacroiliac joint with periarticular sclerosis with no signs of osteitis or bone marrow edema. Her condition was attributed to a known diagnosis of X-linked hypophosphatemic rickets affecting her sacroiliac joints. Her symptoms gradually improved after conservative treatment with physical therapy, nonsteroidal anti-inflammatory drugs, phosphate, and vitamin D supplementations. Based on our literature review, we have come across only five rickets cases with similar presentations. Two patients had previously undiagnosed hypophosphatemic rickets at 15 and 35 years of age. One case was related to vitamin D-deficient rickets, and the final two cases were adult-onset vitamin D-resistant rickets misdiagnosed as ankylosing spondylitis. Radiological signs of sacroiliac joint involvement in these cases include narrowing of the sacroiliac joints, fusion of the sacroiliac joints, subchondral hypointense signal changes, and chondral surface irregularities. Vitamin D supplementation has significantly reduced the incidence of rickets; however, there are still cases of familial rickets that can present with a variety of symptoms, including signs and symptoms consistent with inflammatory spondylitis, which can be easily misdiagnosed or mistreated if this presentation is not recognized.