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Rickets is a paediatric bone disorder characterised by defective mineralisation of bony matrix due to abnormalities in calcium and phosphate metabolism. Despite being a common disease globally, literature on the anaesthetic concerns in rickets are scant. Herein, we describe the management of a 12-year-old child with symptomatic vitamin D deficiency rickets with secondary hyperparathyroidism, undergoing general anaesthesia for an urgent orthopaedic procedure. There are numerous risks involved in such a case, such as hypocalcemia, hypophosphatemia, chest and vertebral deformities, restrictive lung disease, difficult intubation and weaning, difficult regional anaesthesia, chronic bone pain, infectious complications and postoperative decreased renal function, all of which require careful preoperative assessment and risk stratification. In elective surgeries, it is important to optimise the metabolic parameters before taking up the case. However, in urgent and emergent procedures like ours, it is imperative to take up the case after informing the parents of the risks involved., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Dent disease is a rare disease with proximal renal tubular dysfunction, and is characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and chronic kidney disease. Renal failure slowly progresses and end-stage renal disease may develop in the late decades of life. We report a case of a 15-year-old boy who was diagnosed with Dent disease 1 with a CLCN5 truncating mutation. The patient presented with arthralgia and rickets at the onset of Dent disease and he was diagnosed with end-stage renal disease at the age of 15 years. His only symptoms were arthralgia and rickets during the disease course. The findings in this case suggest that patients with arthralgia and rickets could have a rare cause such as Dent disease., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Rickets results from defective bone mineralization, leading to skeletal deformities. Among those deformities, rickets has been associated with craniosynostosis, the premature closure of cranial sutures. Most of these patients have fusion of major sutures. Rarely, squamosal craniosynostosis in association with rickets has been described. Squamosal craniosynostosis is noted as lacking a definitive head abnormality and difficult visualization on standard imaging modalities, leading to poor recognition. Careful attention should be given to rickets patients to monitor for these unusual suture closures. Additionally, craniosynostosis could be a presenting feature of rickets, and further rickets evaluation of the patient is indicated., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Tumor-induced osteomalacia (TIO), a rare paraneoplastic syndrome is seen in association with the overproduction of fibroblast growth factor-23 (FGF-23) by certain mesenchymal tumors in adults. In children, these phosphaturic mesenchymal tumors produce features of rickets similar to TIO. This condition is characterized by elevated blood levels of FGF-23, low phosphate, low or normal active vitamin D, and high alkaline phosphatase. Though the removal of the tumor is curative; in cases where surgical resection is not possible, medical treatment is successful with phosphate and active vitamin D in the improvement of symptoms. The case of a child with features of rickets is presented here to illustrate the importance of identifying this rare condition and instituting appropriate intervention., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Nutritional rickets may be a preventable cause of craniosynostosis. This potential association is under-recognised. A late diagnosis of craniosynostosis may result in reduced brain growth, raised intracranial pressure and long-term psychosocial problems. We present four cases of craniosynostosis associated with nutritional rickets. Those who had delayed presentation underwent emergency craniotomy. Treatment of nutritional rickets and early identification of craniosynostosis can reduce morbidity in these children. [ABSTRACT FROM AUTHOR]

Patients being reported for vitamin D deficiency (VDD) are increasing, particularly among the children and adolescents. This study aims to manifest the clinical and dental evaluations of a child with VDD, referred to the dental office. A 10-year-old British Asian boy was referred to the paediatric specialist dentistry clinic by the general dentist for dental management. The medical history depicted that the patient was diagnosed with VDD, secondary hyperparathyroidism and delayed growth. Moreover, his mother had the VDD during pregnancy. The patient was breast fed and had rickets in infancy. He was prescribed vitamin D supplements at the age of 16 months. He had received multiple dental treatments under local anaesthesia but with limited cooperation. Clinical examination revealed that the patient had chronological enamel hypoplasia shown as bands at the occlusal third on specific teeth. Suboptimal hygiene with general plaque induced gingivitis, dental caries in permanent and primary teeth, and delayed the teeth eruption. Preventions included appropriate oral hygiene and dietary advice, fluoride varnish application and fissure sealant placement. The treatments included anterior direct composite restoration, posterior composite restoration, stainless steel crowns and extractions. Thorough medical history is essential to understand the underlying causes of dental defects. Early dental intervention can restore the patient appearance and function and prevent further dental damage., Competing Interests: The authors declare no conflict of interest., (©2024 The Author(s). Published by MRE Press.)

Background: Vitamin D deficiency is an importance preventable problem in the global and associates with lack levels of awareness about vitamin D. According to prior studies, in the Arab world, there is low of knowledge and awareness toward vitamin D deficiency. The target of our study is evaluating the knowledge level about vitamin D deficiency and determining the associated factors with levels of awareness of its., Method: This online cross-sectional study was performed in Syria between 25 February to 29 March 2023 to assess the levels of knowledge about vitamin D deficiency among general Syrian population. The study's survey was obtained from previously published research and we conducted a pilot study to assure the validity and clarity questionnaire. All Syrian individuals aged 18 or older who were able to read and write and willing to participate were included, while, non-Syrian nationality individuals and all medical staff (doctors, nurses, and medical students…), as well, those under 18 age were excluded. The questionnaire consisted of 23 questions separated into four categories. The first section was sociodemographic information of the study population. The second section measured the level awareness of the study population regarding the benefits of vitamin D. In addition, the third and fourth part evaluated knowing of the respondents about sources of and toxicity consequences of vitamin D. The data were analyzed by utilizing multivariate logistic regression in IBM, SPSS V.28 version., Results: Overall, 3172 of the study population accepted to participate in this research and 57.9% the majority of them were aged in the range among 18 and 28. While, the average age of the respondents were 30.80 ± 11.957. Regarding with the awareness toward knowledge of advantages and source of vitamin D and outcomes of vitamin D toxicity. Most of the participants mentioned that vitamin D is used to treat bone disease and rickets and contributes in maintaining calcium and phosphates (91.4% and 84.6%, respectively). Whereas, more than half of them reported that sun exposure does not cause vitamin D poisoning and that vegetarians are more likelihood to have vitamin D than non-vegetarians, (54.1% and 54.9%, respectively). Only, age and occupation out of nine predictors variables were significantly correlated with adequate knowledge of Vitamin D (p-value < 0.05). The respondents aged more than 60 years were high probability to have good recognition of Vitamin D than participants aged between 18 and 28 years. (OR = 7.95). Retired participants have shown lower aware of Vitamin D 0.38 times than students., Conclusion: Our research revealed that most of the participated individuals have sufficient comprehension about vitamin D, despite, there were significant gap. Health education via programs by government health-care agencies, NGOs and social workers is necessary to increase the awareness and knowledge toward benefits, source, deficiency and toxicity of vitamin D to avoid injury several diseases such as rickets., (© 2024. The Author(s).)

We report clinical and etiological profile of 19 children (10 males) with renal rickets managed in the years 2021-2022. Median (IQR) age of presentation was 60 (18-96) months. The commonest cause was renal tubular acidosis (n=8). Genetic analysis revealed the diagnosis in 83% subjects (5 out of 6 tested).

Family with sequence similarity 20-member C (FAM20C) is a kinase specific to most of the secreted phosphoproteome. FAM20C has been identified as the causative gene of Raine syndrome, initially characterized by lethal osteosclerosis bone dysplasia. However, since the identification of the cases of nonlethal Raine syndrome characterized by hypophosphatemia rickets, the previous definition of Raine syndrome has become debatable and raised a question about the role of mutations of FAM20C in controversial skeletal manifestation in the two forms of the disease. In this study, we aimed to investigate the influence of FAM20C mutations on skeletogenesis. We developed transgenic mice expressing Fam20c mutations mimicking those associated with human lethal and nonlethal Raine syndrome. The results revealed that transgenic mice expressing the mutant Fam20c found in the lethal (KO;G374R) and nonlethal (KO;D446N) Raine syndrome exhibited osteomalacia without osteosclerotic features. Additionally, both mutants significantly increased the expression of the Fgf23, indicating that Fam20c deficiency in skeletal compartments causes hypophosphatemia rickets. Furthermore, as FAM20C kinase activity catalyzes the phosphorylation of secreted proteomes other than those in the skeletal system, global FAM20C deficiency may trigger alterations in other systems resulting in osteosclerosis secondary to hypophosphatemia rickets. Together, the findings of this study suggest that FAM20C deficiency primarily causes hypophosphatemia rickets or osteomalacia; however, the heterogeneous skeletal manifestation in Raine syndrome was not determined solely by specific mutations of FAM20C. The findings also implicated that rickets or osteomalacia caused by FAM20C deficiency would deteriorate into osteosclerosis by the defects from other systems or environmental impacts., (© 2023 Wiley Periodicals LLC.)

Rickets is a disorder of defective mineralisation of the growth plate. Vitamin D deficiency remains the leading cause of nutritional rickets worldwide.We present the case of a 3.5-year-old breastfed boy who presented with dental abscess when a history of developmental regression was noted. Clinical assessment revealed hypotonia, poor growth and stunting. Biochemistry identified hypocalcaemia (1.63mmol/L, [normal range (NR) 2.2-2.7mmol/L]), severe vitamin D deficiency (25hydroxyvitamin D 5.3nmol/L, [NR > 50nmol/L]) with secondary hyperparathyroidism (Parathormone 159pmol/L, [NR 1.6-7.5pmol/L]) and rickets on radiographs. Growth failure screening suggested hypopituitarism with central hypothyroidism and low IGF1 at baseline, however, dynamic tests confirmed normal axis. Management included nasogastric nutritional rehabilitation, cholecalciferol and calcium supplementation and physiotherapy. A good biochemical response in all parameters was observed within 3 weeks and reversal of developmental regression by 3 months from treatment. Developmental regression as a presentation of nutritional rickets is rare and requires a high index of suspicion., (© 2023. Crown.)

Background: Nutritional rickets (NR) is still a major problem and is exacerbated by an increasing influx of immigrants. In this study, Turkish and immigrant cases followed with the diagnosis of NR in our pediatric endocrinology clinic were retrospectively evaluated., Methods: Detailed data of cases diagnosed with NR between 2013 and 2020 and followed for at least six months were reviewed., Results: In the study period, 77 cases of NR were identified. Turkish children constituted 76.6% (n=59) while 18 (23.4%) were immigrant children. The mean age at diagnosis was 8.1±7.8 months, 32.5% (n=25) were female, and 67.5% (n=52) were male. The 25-hydroxyvitamin D3 was below normal in all patients, with a mean value of 4.3±2.6 ng/mL. Parathyroid hormone (PTH) was above normal in all and the mean value was 301.7±139.3 pg/ mL. While there were 3.9 cases of NR in 10,000 endocrine clinic patients in 2013, this rate increased more than four-fold to 15.7 patients in 2019., Conclusions: Despite the vitamin D prophylaxis program in Türkiye, NR is seen significantly more frequently in recent years, which may be associated with an increasing number of refugees. High PTH levels indicate the severity of NR cases admitted to our clinic. However, clinically significant NR is only the tip of the iceberg and the true burden of subclinical rickets is unknown. Increasing compliance with the vitamin D supplementation program in refugee and Turkish children is important for the prevention of nutritional rickets.

To better understand the causes of hypophosphatemia in children, we evaluated all serum phosphate tests performed in a tertiary hospital with unexpected but persistent temporary or isolated hypophosphatemia over an 18 year period. We collected 29,279 phosphate tests from 21,398 patients, of which 268 (1.2%) had at least one result showing hypophosphatemia. We found that endocrinopathies (n = 60), tumors (n = 10), and vitamin D deficiency (n = 3) were the medical conditions most commonly associated with mild hypophosphatemia, but in many patients the cause was unclear. Among patients with endocrinopathies, those with diabetes mellitus were found to have lower mean serum phosphate levels (mean 3.4 mg/dL) than those with short stature (3.7 mg/dL) or thyroid disorders (3.7 mg/dL). In addition, we found a correlation between glycemia and phosphatemia in patients with diabetes. However, despite the potential relevance of monitoring phosphate homeostasis and the underlying etiologic mechanisms, renal phosphate losses were estimated in less than 5% of patients with hypophosphatemia. In the pediatric age group, malignancies, hypovitaminosis D, and endocrine disorders, mostly diabetes, were the most common causes of hypophosphatemia. This real-world study also shows that hypophosphatemia is frequently neglected and inadequately evaluated by pediatricians, which emphasizes the need for more education and awareness about this condition to prevent its potentially deleterious consequences.

Vitamin D has a well-known role in the calcium homeostasis associated with the maintenance of healthy bones. It increases the efficiency of the intestinal absorption of dietary calcium, reduces calcium losses in urine, and mobilizes calcium stored in the skeleton. However, vitamin D receptors are present ubiquitously in the human body and indeed, vitamin D has a plethora of non-calcemic functions. In contrast to most vitamins, sufficient vitamin D can be synthesized in human skin. However, its production can be markedly decreased due to factors such as clothing, sunscreens, intentional avoidance of the direct sunlight, or the high latitude of the residence. Indeed, more than one billion people worldwide are vitamin D deficient, and the deficiency is frequently undiagnosed. The chronic deficiency is not only associated with rickets/osteomalacia/osteoporosis but it is also linked to a higher risk of hypertension, type 1 diabetes, multiple sclerosis, or cancer. Supplementation of vitamin D may be hence beneficial, but the intake of vitamin D should be under the supervision of health professionals because overdosing leads to intoxication with severe health consequences. For monitoring vitamin D, several analytical methods are employed, and their advantages and disadvantages are discussed in detail in this review.

(1) Background: In the present paper we aimed to review the evidence about the potential implication of vitamin D in the pathogenesis and management of systemic sclerosis (SSc); (2) Methods: we performed a review of the literature looking for studies evaluating the potential role of vitamin D and its analogs in SSc. We searched the PubMed, Medline, Embase, and Cochrane libraries using the following strings: (vitamin D OR cholecalciferol) AND (systemic sclerosis OR scleroderma). We included cohort studies, case-control studies, randomized controlled trials, and observational studies. (3) Results: we identified nine pre-clinical and 21 clinical studies. Pre-clinical data suggest that vitamin D and its analogs may suppress fibrogenesis. Clinical data are concordant in reporting a high prevalence of hypovitaminosis D and osteoporosis in SSc patients; data about the association with clinical manifestations and phenotypes of SSc are, conversely, far less consistent; (4) Conclusions: in vitro data suggest that vitamin D may play an antifibrotic role in SSc, but clinical data confirming this finding are currently lacking. Hypovitaminosis D is common among SSc patients and should be treated to reduce the risk of osteoporosis.

X-linked hypophosphatemia (XLH) is the most common form of inheritable rickets. The disease is caused principally by PHEX mutations leading to increased concentrations of circulating intact FGF23, hence renal phosphate wasting, hypophosphatemia, and decreased circulating levels of 1,25(OH) 2 vitamin D. The chronic hypophosphatemia leads to rickets and osteomalacia through a combination of mechanisms, including a lack of endochondral ossification and impaired mineralization. Imaging has a major role in determining the diagnosis of rickets and its cause, detecting complications as early as possible, and helping in treatment monitoring., (Copyright © 2021. Published by Elsevier Masson SAS.)

An elevated serum alkaline phosphatase (ALP) level is one of the markers for the presence of rickets in children, but it is also associated with bone formation. However, its role in diagnosing genu varum in pediatric patients with vitamin D-deficient rickets is still unknown. To clarify the role of the serum ALP level in assessing the severity of genu varum, we retrospectively investigated this issue statistically using data on rickets such as serum intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, ALP, the level of creatinine as the percentage of the median according to age (%Cr), and the metaphyseal diaphyseal angle (MDA) in the lower extremities as an index of the severity of genu varum. A multiple regression analysis revealed that log ALP and %Cr values were negatively associated with MDA values. The former association was also confirmed by a linear mixed model, while iPTH was positively associated with MDA by path model analysis. To elucidate the association of ALP with MDA in the presence of iPTH, we investigated three-dimensional figures by neural network analysis. This indicated the presence of a biphasic association of ALP with MDA: the first phase increases while the second decreases MDA. The latter phenomenon is considered to be associated with the increase in bone formation due to the mechanical stress loaded on the lower extremities. These findings are important and informative for pediatricians to understand the significance of the serum ALP level in pediatric patients with genu varum caused by vitamin D deficiency.

During the last two decades, the potential impact of vitamin D on the risk of cardiovascular disease (CVD) has been rigorously studied. Data regarding the effect of vitamin D on CVD risk are puzzling: observational data indicate an inverse nonlinear association between vitamin D status and CVD events, with the highest CVD risk at severe vitamin D deficiency; however, preclinical data and randomized controlled trials (RCTs) show several beneficial effects of vitamin D on the surrogate parameters of vascular and cardiac function. By contrast, Mendelian randomization studies and large RCTs in the general population and in patients with chronic kidney disease, a high-risk group for CVD events, largely report no significant beneficial effect of vitamin D treatment on CVD events. In patients with rickets and osteomalacia, cardiovascular complications are infrequently reported, except for an increased risk of heart failure. In conclusion, there is no strong evidence for beneficial vitamin D effects on CVD risk, either in the general population or in high-risk groups. Whether some subgroups such as individuals with severe vitamin D deficiency or a combination of low vitamin D status with specific gene variants and/or certain nutrition/lifestyle factors would benefit from vitamin D (metabolite) administration, remains to be studied.

Defective mineralization of the growth plate and preformed osteoid result in rickets and osteomalacia, respectively. The leading cause of rickets worldwide is solar vitamin D deficiency and/or dietary calcium deficiency collectively termed as nutritional rickets. Vitamin D deficiency predominates in high-latitude countries in at-risk groups (dark skin, reduced sun exposure, infants and pregnant and lactating women) but is emerging in some tropical countries due to sun avoidance behaviour. Calcium deficiency predominates in tropical countries, especially in the malnourished population. Nutritional rickets can have devastating health consequences beyond bony deformities (swollen wrist and ankle joints, rachitic rosary, soft skull, stunting and bowing) and include life-threatening hypocalcaemic complications of seizures and, in infancy, heart failure due to dilated cardiomyopathy. In children, diagnosis of rickets (always associated with osteomalacia) is confirmed on radiographs (cupping and flaring of metaphyses) and should be suspected in high risk individuals with the above clinical manifestations in the presence of abnormal blood biochemistry (high alkaline phosphatase and parathyroid hormone, low 25-hydroxyvitamin D and calcium and/or low phosphate). In adults or adolescents with closed growth plates, osteomalacia presents with non-specific symptoms (fatigue, malaise and muscle weakness) and abnormal blood biochemistry, but only in extreme cases, it is associated with radiographic findings of Looser's zone fractures. Bone biopsies could confirm osteomalacia at earlier disease stages, for definitive diagnosis. Treatment includes high-dose cholecalciferol or ergocalciferol daily for a minimum of 12 wk or stoss therapy in exceptional circumstances, each followed by lifelong maintenance supplementation. In addition, adequate calcium intake through diet or supplementation should be ensured. Preventative approaches should be tailored to the population needs and incorporate multiple strategies including targeted vitamin D supplementation of at-risk groups and food fortification with vitamin D and/or calcium. Economically, food fortification is certainly the most cost-effective way forward., Competing Interests: None

Case: A preterm neonate with biochemical rickets is found to have a Monteggia fracture. The infant underwent percutaneous pinning. There was loss of fixation; however, the infant has been followed since discharge from the hospital and has completely healed with full range of motion., Conclusions: The medical management of this entity involves enteral feedings and optimization of nutrients. The optimal surgical treatment of this injury in the neonatal period is not yet known, although percutaneous pinning resulted in normal healing and function. These aspects require clinician awareness of this unique fracture type in a premature patient with fragile bone.

A wide of array of patients with genetic and metabolic conditions present with orthopedic manifestations. This article discusses the most common conditions seen in a typical pediatric orthopedic practice. A few pearls are highlighted for each condition to alert practitioners to some of the pitfalls encountered when treating these often highly challenged children., (Copyright © 2019 Elsevier Inc. All rights reserved.)

To report prospectively the radioclinical outcome of guided growth surgery for coronal plane deformities around the knee in young children with nutritional rickets on the intermediate term, to assess the responsiveness of torsional deformities of the tibias to guided growth regarding function and objective clinical parameters, and to propose a treatment algorithm., Methods: Fifty children (male:female, 27:23) with knee coronal plane deformities (knees:physes, 86:99), (varum:valgum, 51:35) secondary to nutritional rickets were subjected to femoral and/or tibial temporary hemiepiphysiodesis using a two-hole 8-plate. The mean age at implantation was 3.8 ± 1.5 years (range 2.5 to 5). The mean follow-up was 2.8 years (range 2 to 4). All children received a standing full-length AP radiographs of both lower limbs in neutral rotation to measure the mechanical axis deviation, tibiofemoral angle, and joint orientation angles. Tibial torsion was objectively assessed by measuring the bimalleolar axis., Results: The radiologic measurements, tibiofemoral angle, mechanical axis deviation, mechanical lateral distal femoral angle, medial proximal tibial angle, and Hilgenreiner-epiphyseal angle, showed a highly statistically significant improvement ( P ≤ 0.001). Radiographic outcomes correlated with their clinical counterparts. The mean duration of correction of the mechanical axis was 10.8 ± 2.4 months (7 to 21). The mean follow-up for rebound of the deformity was 1.5 years (range 1 to 3)., Conclusion: The radioclinical outcome is rewarding with a tolerable complication profile. The mechanical complications were mostly related to lengthy implant retainment encountered in severe deformities. Internal tibial torsion seems profoundly responsive to correction of coronal plane deformity. And, derotation osteotomies are rarely justified. Our proposed algorithm may be used as a decision-taking guide for achieving the desired growth modulation in a more efficient manner., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Background: Craniosynostosis has a known association with rickets. Because of abnormal bone development and a tendency for patients with rickets to present at an older age than most patients with craniosynostosis, repair may be complicated by inadequate cranial expansion and greater risk of sutural re-fusion. We present 2 cases of rickets-associated sagittal craniosynostosis and show the effectiveness of distraction osteogenesis in the surgical management of this condition., Case Description: Two 3-year-old boys with rickets presented with sagittal synostosis and marked scaphocephalic deformity. Cranial osteotomies were performed followed by placement of 2 internal distractors. The devices were activated daily for 30 days to achieve a target transverse cranial distraction of 30 mm. A subsequent period of 10-12 weeks allowed for adequate bone consolidation. At the time of device removal, the final breadth of distraction and the quality of new bone formed was assessed. Distraction distance in both cases was verified intraoperatively to be 30 mm. Clinical examination confirmed that the distraction gaps were bridged by solid bone. The treatment protocol resulted in a significant improvement in cranial proportion in both patients, which was maintained at long-term follow-up. Estimated blood loss was high in both cases, presumably related to the hyperemic nature of rickets bone., Conclusions: Distraction osteogenesis promotes bone growth and cranial remodeling in patients with craniosynostosis caused by rickets. The technique allows for continuous incremental expansion of both bone and scalp tissue. We recommend consideration of distraction osteogenesis in the treatment of older children with severe deformity related to craniosynostosis, including those with rickets., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Some metabolic bone disorders may result in the premature closure of one or more calvarial sutures during childhood, potentially leading to a cranioencephalic disproportion. The aim of this paper is to review the characteristics and consequences of craniosynostosis associated with metabolic disorder., Material and Methods: A review of the literature on metabolic forms of craniosynostosis was performed., Results: The most common forms of craniosynostosis associated with metabolic bone disorder were isolated sagittal suture fusion with or without scaphocephaly, and sagittal suture fusion associated with coronal suture fusion (oxycephaly) or also with lambdoid suture fusion (pansynostosis). Synostosis may be well-tolerated, but in some subjects results in neurodevelopmental and functional impairment that is sometimes severe., Conclusion: The impact of metabolic synostosis is very variable, depending on the specific underlying metabolic disease, with a large spectrum of morphological and functional consequences. Diagnosis should be early and management should be carried out by a multidisciplinary team with expertise in both rare skeletal disorders and craniosynostosis. The impact of emergent medical therapies recently developed for some of these diseases will be assessed by systematic coherent follow-up of international registries., (Copyright © 2019. Published by Elsevier Masson SAS.)

This report describes the oral manifestations of renal tubular acidosis (RTA) associated with secondary rickets and discusses the biological plausibility of these findings. The characteristic electrolyte changes during RTA or genetic mutations that trigger RTA may be responsible for impaired amelogenesis, dental malocclusion, impacted teeth, and absent lamina dura. This report reinforces the possibility of an association between RTA and the oral manifestations described.

Background: The aim was to clarify whether children born preterm with a history of necrotizing enterocolitis (NEC) had an increased risk of rickets, fractures, and/or vitamin D deficiency during childhood and adolescence compared to controls without NEC, matched for gestational age., Methods: All infants born in Sweden between 1987 and 2009 with a gestational age <32 + 0 weeks and a diagnosis of NEC were identified. Totally, 465 children with a history of NEC and 2127 controls were included. International Classification of Diseases codes for all categories of fractures, rickets, vitamin D deficiency, and malnutrition were analyzed., Results: In total, 94 of the 465 children with NEC died within 28 days. Of the 2127 controls, 288 died within 28 days. Among the remaining 371 NEC cases, 39 fracture occasions were identified. The 1839 controls had 204 fracture occasions. There was no significant difference in fractures. Rickets was diagnosed in 11 (3%) of the children with a history of NEC compared to 21 (1%) of the controls (odds ratio 2.65, 95% CI 1.26-5.53, p = 0.007)., Conclusions: This study showed an increased risk of rickets but not fractures during childhood and adolescence in children born preterm and with a history of NEC, compared to matched controls.

Infantile-onset Pompe disease is a lysosomal storage disorder characterised with hypertrophic cardiomyopathy, respiratory insufficiency, and hypotonia. Dilated cardiomyopathy is an extremely rare and curable complication of nutritional hypocalcaemic rickets. A 3-month-old female infant was referred to our paediatric ICU with a 4-day history of fatigue, tachypnoea, tachycardia, hypoxia, and respiratory failure. According to the laboratory, radiology, and echocardiography findings, she was first diagnosed with nutritional hypocalcaemic rickets-related dilated cardiomyopathy, but vitamin D and elementary calcium supplementation unmasked the underlying infantile-onset Pompe disease. Nutritional hypocalcaemic rickets and infantile-onset Pompe disease must always be kept in mind among the causes of concomitant dilated cardiomyopathy and hypertrophic cardiomyopathy.

Competing Interests: Competing interests: None declared.

Background: There's abundant sunshine in the tropics but severe rickets is still observed. Nutritional rickets is associated with an increased risk of acute lower respiratory infections. Pneumonia is the leading cause of death in the under 5 -year old children with the highest burden in developing countries. Both Pneumonia and rickets are common in the developing countries and may affect clinical presentation and outcome. This study aimed to determine the prevalence and associated factors of nutritional rickets in children admitted with severe pneumonia., Methods: This was a cross-sectional study of children aged 2-59 months presenting with severe pneumonia at an emergency unit. We enrolled 221 children between February and June 2012 after consent. A pre-coded questionnaire was used to collect data on socio-demographic, nutritional and past medical history. Physical exam was done for signs of rickets and anthropometric measurements. Serum calcium, phosphorus, and alkaline phosphatase (ALP) were assessed. Children with any physical signs of rickets or biochemical rickets (ALP > 400 IU); had a wrist x-ray done. Nutritional rickets was defined as the presence of radiological changes of cupping or fraying and/ or metaphyseal thickening. Severe pneumonia was defined using the WHO criteria. Statistical analysis was performed using the Stata 10 statistical package. P- value < 0.05 was significant., Results: The prevalence of nutritional rickets among children with severe pneumonia is 9.5%. However, 14.5% had raised ALP (biochemical rickets). The factors independently associated with rickets was an elevated alkaline phosphatase; p-value < 0.001, or 32.95 95% CI (10.54-102.93). Other factors like breastfeeding, big family size, birth order were not significantly associated with rickets. Low serum calcium was detected in 22 (9.9%) of the 221 participants. Overall few children with rickets had typical clinical features of rickets on physical examination., Conclusion: Rickets is a common problem in our setting despite ample sunshine. Clinicians should actively assess children for rickets in this setting and screen for rickets in those children at high risk even without clinical features.

Background: Whilst hypocalcemic complications from vitamin D deficiency are considered rare in high-income countries, they are highly prevalent among Black, Asian and Minority Ethnic (BAME) group with darker skin. To date, the extent of osteomalacia in such infants and their family members is unknown. Our aim was to investigate clinical, cardiac and bone histomorphometric characteristics, bone matrix mineralization in affected infants and to test family members for biochemical evidence of osteomalacia., Case Presentation: Three infants of BAME origin (aged 5-6 months) presented acutely in early-spring with cardiac arrest, respiratory arrest following seizure or severe respiratory distress, with profound hypocalcemia (serum calcium 1.22-1.96 mmol/L). All infants had dark skin and vitamin D supplementation had not been addressed during child surveillance visits. All three had severely dilated left ventricles (z-scores + 4.6 to + 6.5) with reduced ejection fraction (25-30%; normal 55-70), fractional shortening (7 to 15%; normal 29-40) and global hypokinesia, confirming hypocalcemic dilated cardiomyopathy. They all had low serum levels of 25 hydroxyvitamin D (25OHD < 15 nmol/L), and elevated parathyroid hormone (PTH; 219-482 ng/L) and alkaline phosphatase (ALP; 802-1123 IU/L), with undiagnosed rickets on radiographs. One infant died from cardiac arrest. At post-mortem examination, his growth plate showed a widened, irregular zone of hypertrophic chondrocytes. Histomorphometry and backscattered electron microscopy of a trans-iliac bone biopsy sample revealed increased osteoid thickness (+ 262% of normal) and osteoid volume/bone volume (+ 1573%), and extremely low bone mineralization density. Five of the nine tested family members had vitamin D deficiency (25OHD < 30 nmol/L), three had insufficiency (< 50 nmol/L) and 6/9 members had elevated PTH and ALP levels., Conclusions: The severe, hidden, cardiac and bone pathology described here exposes a failure of public health prevention programs, as complications from vitamin D deficiency are entirely preventable by routine supplementation. The family investigations demonstrate widespread deficiency and undiagnosed osteomalacia in ethnic risk groups and call for protective legislation.

Rickets is a bone disease associated with abnormal serum calcium and phosphate levels. The clinical presentation is heterogeneous and depends on the age of onset and pathogenesis but includes bowing deformities of the legs, short stature and widening of joints. The disorder can be caused by nutritional deficiencies or genetic defects. Mutations in genes encoding proteins involved in vitamin D metabolism or action, fibroblast growth factor 23 (FGF23) production or degradation, renal phosphate handling or bone mineralization have been identified. The prevalence of nutritional rickets has substantially declined compared with the prevalence 200 years ago, but the condition has been re-emerging even in some well-resourced countries; prematurely born infants or breastfed infants who have dark skin types are particularly at risk. Diagnosis is usually established by medical history, physical examination, biochemical tests and radiography. Prevention is possible only for nutritional rickets and includes supplementation or food fortification with calcium and vitamin D either alone or in combination with sunlight exposure. Treatment of typical nutritional rickets includes calcium and/or vitamin D supplementation, although instances infrequently occur in which phosphate repletion may be necessary. Management of heritable types of rickets associated with defects in vitamin D metabolism or activation involves the administration of vitamin D metabolites. Oral phosphate supplementation is usually indicated for FGF23-independent phosphopenic rickets, whereas the conventional treatment of FGF23-dependent types of rickets includes a combination of phosphate and activated vitamin D; an anti-FGF23 antibody has shown promising results and is under further study.

Nutritional rickets remains a significant public health issue for children worldwide. Although it has almost disappeared in industrialized countries following routine vitamin D supplementation, recent evidence suggests an increasing incidence, especially in young children. In addition to the classical clinical consequences on bone and the growth plate, rickets may also be associated with life-threatening neurological and cardiac complications in the most severe forms. Consequently, early screening and treatment are required. Here, we report the case of a 2-year-old child who presented with severe nutritional rickets associated with seizure and cardiomyopathy. Family screening revealed rickets in all the siblings. This case report emphasizes the importance of being aware of this disease, notably in population with sociocultural risk factors., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: Stoss vitamin D treatment has been recommended for its non-skeletal benefits in adults, but there is a lack of data on the optimal dose of vitamin D stoss therapy in children with vitamin D deficiency/insufficiency without rickets. This study aimed to compare efficiency/side effects of two different stoss therapy regimens (10 000 IU/kg and 300 000 IU vitamin D3) administered in children with vitamin D deficiency/insufficiency without rickets., Methods: Sixty-four children who had vitamin D deficiency/insufficiency were studied. A serum 25-hydroxyvitamin-D (25-OH-D) level of 15-20 ng/mL was considered as vitamin D insufficient and <15 ng/mL was considered as vitamin D deficient. The patients were divided into two groups according to the stoss therapy doses they received. Serum calcium, phosphate, alkaline phosphatase, 25-OH-D, parathyroid hormone levels, and spot urine calcium/creatinine ratios before/after treatment were recorded. Wrist radiography and renal ultrasonography were performed., Results: The mean age of the subjects was 10.6±4.4 years. Thirty-two children were treated with a single vitamin D3 dose of 10 000 IU/kg and 32 patients received 300 000 IU. No difference was found in 25-OH-D levels between the two groups at presentation. The mean level of 25-OH-D was higher in the 10 000 IU/kg group at the second week of therapy. There was no difference between the groups at post-treatment weeks 4 and 12. The 25-OH-D was found to be below optimal levels (≥30 ng/mL) in 66.5% and <20 ng/mL in 21.8% of patients at the third month in both groups. None developed hypercalcemia and/or hypercalciuria. Nephrolithiasis was not detected in any patient., Conclusion: This study showed that both doses of stoss therapy used in the treatment of vitamin D insufficiency/deficiency are effective and safe. However, an optimal level of 25-OH-D cannot be maintained for more than three months.

Purpose: Treatment of renal calculi in patients with severe skeletal deformities can be challenging. We present our experience in order to provide an assessment of technical difficulties, associated complications, and outcomes of percutaneous nephrolithotomy (PCNL) as a treatment option in this special patient group., Materials and Methods: Our study included eight patients treated with PCNL for renal stones. All had severe skeletal deformities including six with severe kyphoscoliosis, one with osteogenesis imperfecta, and another withrickets. After pre-operative evaluation the procedure was performed under fluoroscopic and/or ultrasonic guidance. In all but one case, PCNL was performed with the patient in the prone position. Silicone rolls and soft padded bolsters were used to obtain the best positioning for the procedure. Clearance rates and complications were assessed., Results: Complete stone-free rate was achieved in six patients (75%) after first-PCNL. The two patients with residual stones underwent a second-look PCNL, after which one was completely cleared. The overall completestone-free rate after second PCNL was 87%. Only minor complications were seen in two patients (25%)., Conclusion: We found PCNL to be safe and effective for managing kidney stones in patients with severe skeletal deformities.

Introduction: Defective mineralization of osteoid matrix prior to physeal closure causes rickets. Poor calcification of the cartilage matrix in the zone of provisional calcification causes flattened skull, rachitic rosary, bowed legs, coxa vara and brittle bones. The recent literature has seen an increase in the incidence of the disease in both developing and developed nations. We evaluated behaviour of lower limb deformities due to nutritional rickets in 117 patients., Materials and Methods: A prospective study was conducted from January 2009 to December 2011 for clinical and radiological evaluation of knee deformities in nutritional rickets. A total of 117 patients with 198 coronal plane knee deformities between 2 years and 12 years age of rickets were enrolled in this study., Results: In our study, there were 65 genu varum and 133 genu valgum deformities. Seven genu varum (10.7%) and 37 genu valgum (28%) deformities were regarded as failure. Fifty eight genu varum got corrected completely obtaining an average of 5° of valgum in an average of 6.3 months. The average rate of spontaneous correction was 1.9° a month. Ninety six valgum got corrected obtaining an average of 4.7 valgum in an average of 13.3 months. The average rate of spontaneous correction was 0.92° a month., Conclusion: Most of the rachitic deformities get corrected with age. Genu varum is having better chances and a faster rate of correction as compared with genu valgum. Early surgery may be indicated in late presenting cases. We believe varum above 4 years and 18° of valgum above 9 years usually do not correct and may require surgical intervention.

Nutritional or classical rickets (here labeled as "rickets") is a worldwide disease involving mostly infants and young children having inadequate sunlight exposure, often associated with a low dietary intake of Vitamin D. Rickets targets all layers of society independently of economic status with historical information spanning more than two millennia. Vitamin D is critical for the absorption of calcium and prevention of rickets in children as well as osteomalacia in adults. The initial and misleading paradigm of the 19th and 20th centuries that rickets may have been the consequence of infection has been, indeed, reversed following the identification of the Vitamin D molecule's important role in the function of the immune system. Although traditionally considered limited to osteopathology, Vitamin D deficiency is now known to be linked to infection, inflammation, and carcinogenesis. In this review, we consider the key historical (Whistler, pre-Whistler and post-Whistler descriptors) and social facts around rickets; highlight the osteo-pathological features of rickets and the pathology of the upper and lower respiratory tract, stressing the fact that lungs remain the main secondary organ affected by Vitamin D deficiency; and emphasize the public health role in identifying the cases of child neglect or abuse based on the evaluation of the costochondral region., Competing Interests: The authors declare no conflict of interest.

Background: Although mucolipidosis type II has similar metabolic abnormalities to those found in all the mucopolysaccharidoses and mucolipidoses, there are distinctive diagnostic radiographic changes of mucolipidosis II in the perinatal/newborn/infant period., Objective: To describe the early characteristic radiographic changes of mucolipidosis II and to document when these changes manifest and resolve., Materials and Methods: We retrospectively reviewed radiographs and clinical records of 19 cases of mucolipidosis II from the International Skeletal Dysplasia Registry (1971-present; fetal age to 2½ years). A radiologist with special expertise in skeletal dysplasias evaluated the radiographs., Results: The most common abnormalities were increased vertebral body height (80%, nonspecific), talocalcaneal stippling (86%), periosteal cloaking (74%) and vertebral body rounding (50%). Unreported findings included sacrococcygeal sclerosis (54%) and vertebral body sclerosis (13%). Rickets and hyperparathyroidism-like (pseudohyperparathyroidism) changes (rarely reported) were found in 33% of cases. These changes invariably started in the newborn period and resolved by 1 year of age. The conversion from these early infantile radiographic features to dysostosis multiplex changes occurred in 41% of cases, and within the first year after birth., Conclusion: Several findings strongly suggest the diagnosis of mucolipidosis II, including cloaking in combination with one or more of the following radiographic criteria: talocalcaneal stippling, sacrococcygeal or generalized vertebral body sclerosis, vertebral body rounding, or rickets/hyperparathyroidism-like changes in the perinatal/newborn/infancy period. These findings are not found in the other two forms of mucolipidosis nor in any of the mucopolysaccharidoses.