Radiological Evidence Of Rickets Research Articles

Clinical and genetic analysis of two Chinese families with vitamin D-dependent rickets type IA and follow-up

ObjectiveVitamin D-dependent rickets type IA (VDDR-IA) is a rare autosomal recessive disorder characterized by the early onset of severe rickets. The objectives of this study were twofold: (1) to analyze the clinical characteristics and therapy of two patients with VDDR-IA from two separate Chinese families, and (2) investigate the CYP27B1 gene mutations in two large pedigrees.MethodsMedical history, clinical manifestations, physical examination, radiological findings and laboratory data were analyzed from two patients with VDDR-IA. Serum 1, 25-dihydroxyvitamin D [1, 25-(OH)2D3] of the two patients and their respective families were measured by ELISA and blood samples from both families was obtained for CYP27B1 gene sequence.ResultsTwo patients had typical manifestations and radiological evidence of rickets. Laboratory data showed hypocalcaemia and hypophosphataemia, along with high levels of serum alkaline phosphatase, parathyroid hormone and 25-hydroxyvitamin D3. However, serum 1,25-(OH)2D3 level were low in the patients but normal in their family members. Genetic sequence identified two patients were homozygous for a duplication mutation in exon 8 of CYP27B1 gene (c.1319_1325dupCCCACCC, p.Phe443Profs * 24). After treating with calcitriol and calcium, there was biochemical improvement with normalization of serum calcium and phosphorus, and radiographic evidence of compensatory skeletal mineralization. One patient developed nephrocalcinosis during follow-up.ConclusionsThis study identified a recurrent seven-nucleotide insertion of CYP27B1 in two large pedigrees, and compared the clinical characteristics and individual therapy of two affected patients. Additionally, our experience further supports the notion that nephrocalcinosis can occur even on standard doses of calcitriol and oral calcium, and normal level of serum calcium, phosphorus, PTH and 25-(OH)D3.

Vitamin D evaluation based on demographics and calcium supplement intake in children suffering from acute febrile illness admitted in as tertiary care center

Background: Vitamin D or sunshine vitamin is a vital steroid group of vitamins with its deficiency being common, especially among children. The literature establishing the correlation of dietary habits with Vitamin D levels in Indian population is scarce. Objective: This study aims to evaluate serum 25-hydroxyvitamin D (25(OH)D) level in the hospitalized children suffering from acute febrile illness (AFI) and find its correlation with calcium intake and demographic characters. Materials and Methods: The study was conducted at the pediatric department of a tertiary hospital of Maharashtra, over a period of 6 months in the children between the age groups of 1 month and 12 years, admitted with AFI and with or without clinical or biochemical evidence of rickets. After detailed history, evaluation of Vitamin D status was done in all children within 48 h of admission to the hospital using early morning sample of 2 ml of serum using chemiluminescent immunoassay method. We correlated Vitamin D levels with socioeconomic status (SES) along with various other parameters like serum calcium (S. calcium). Results: It was observed that with the improvement of SES, the Vitamin D deficiency (VDD) did not improve. The biochemical parameters such as S. calcium and alkaline phosphatase revealed a significant correlation with Vitamin D status. S. calcium level was significantly low in children with VDD. Radiological evidence of rickets was seen only in 40.5% of cases of VDD and 14.3% of cases of Vitamin D insufficiency and thus was not a diagnostic hallmark for rickets. Conclusion: The data suggested that VDD is very common among children aged 1 month–12 years and it is not correlated with SES and calcium intake. Efforts need to be made to improve the Vitamin D status by creating awareness among people.

Multiple fractures in infants who have Ehlers-Danlos/hypermobility syndrome and or vitamin D deficiency: A case series of 72 infants whose parents were accused of child abuse and neglect.

ABSTRACTObjective: To increase the level of awareness that Ehlers-Danlos/hypermobility syndrome (EDS) and vitamin D deficiency are associated with infantile fragility fractures and radiologic features that may be mistakenly reported to be caused by non-accidental trauma due to Child Abuse and Neglect (CAN).Patients and Methods: We constructed a case series, the largest to date, of infants with EDS who were vitamin D sufficient, insufficient and deficient and infants without EDS but with documented vitamin D deficiency and radiologic evidence of rickets who presented with multiple fractures originally diagnosed as being non-accidental and caused by child abuse. These infants were referred to the outpatient Bone Health Care Clinic at Boston University Medical Campus over a 6-year (2010–2015) period. We also present 6 index cases in which the court concluded that there was no convincing evidence of child abuse and the infants were returned to their parents. Institutional Review Board (IRB) approval was obtained.Results: We present 72 cases of infants with multiple fractures diagnosed to be caused by non-accidental trauma. All infants were younger than one year of age. Among them, 93%(67) had clinical evidence of EDS and/or a family history with a confirmed clinical diagnosis of at least one parent having EDS and the other 7%(5) without evidence of EDS had vitamin D deficiency/infantile rickets. Three of the EDS infants were diagnosed as osteogenesis imperfecta (OI)/EDS overlap syndrome. The most common fractures noted at diagnosis were ribs and extremity fractures (including classic metaphyseal lesions). Serum levels of 25-hydroxyvitamin D [25(OH)D] were reported in 48 infants (18.0 ± 8.5 ng/ml) and in 30 mothers (21.3 ± 11.7 ng/ml). Sixty-three percent (27) of the EDS infants who had their serum 25(OH)D measured were vitamin D deficient 25(OH)D<20 ng/ml and 5 were vitamin D sufficient 25(OH)D>30 ng/ml. The mean serum level for infants with vitamin D deficiency/rickets was (10.2 ± 3.0 ng/ml)Conclusion: EDS, OI/EDS and vitamin D deficiency/infantile rickets are associated with fragility fractures in infants that can be misinterpreted as caused by non-accidental trauma due to child abuse.

Effect of intramuscular cholecalciferol megadose in children with nutritional rickets.

The treatment practices for vitamin D deficiency rickets are highly variable. Though a single intramuscular (IM) megadose of vitamin D is economical, and ensures good compliance, it poses the risk of hypervitaminosis D. This observational study was conducted to assess the duration of effect and safety of single IM megadose of cholecalciferol in the treatment of vitamin D deficiency rickets. Children younger than 14 years with rickets were enrolled. Baseline investigations included radiograph of wrists and estimation of serum calcium, phosphate, alkaline phosphatase (ALP), 25(OH) vitamin D and parathormone (PTH) levels. All children received a single IM megadose of vitamin D3. Biochemical parameters were re-evaluated at 1.5, 3 and 6 months after the megadose and the values were compared to the baseline. We enrolled 21 children, out of which nine remained under active follow-up till 6 months. Radiological evidence of rickets was present in all 21 children, 14 had hypocalcemia at the time of presentation. After IM cholecalciferol megadose, median 25 hydroxy vitamin D [25(OH)D] level remained significantly more than the baseline till 6 months after the megadose. At 1.5 months after the vitamin D megadose, three (30%) of the children were found to develop toxic levels of vitamin D (>150 ng/mL), although none had hypercalcemia or any clinical manifestation of vitamin D toxicity. At 3 months and 6 months after the megadose, 25(OH)D levels remained in the sufficient range (20-100 ng/mL) in seven out of the eight children who came for follow-up. A single IM megadose of vitamin D may be effective in significantly increasing the 25(OH)D levels for at least 6 months in children with rickets, but elevation of 25(OH)D to toxic range raises concern regarding its safety.

Vitamin D: A New Promising Therapy for Congenital Ichthyosis.

Severe vitamin D deficiency and rickets are highly prevalent among children with congenital ichthyosis. We report an incidental observation of a dramatic and excellent clinical response with regard to skin scaling and stiffness in children with congenital ichthyosis after short-term high-dose vitamin D supplementation that has not been previously described. Seven children with congenital ichthyosis (5 with autosomal recessive congenital ichthyosis; 2 with epidermolytic ichthyosis) and severe vitamin D deficiency (and/or rickets) were given 60,000 IU of oral cholecalciferol daily for 10 days under supervision. All children were subsequently put on recommended daily allowance of 400 to 600 IU of cholecalciferol. The main outcome measures observed and studied were reduction in skin scaling and stiffness of the extremities. All cases had severe vitamin D deficiency (serum 25-hydroxyvitamin D < 4 ng/mL) and secondary hyperparathyroidism. Six patients had clinical and radiologic evidence of rickets. Significant improvement in scaling was noticeable by day 5, showing further improvement by day 10, in 6 of the 7 cases. At 1 month, the skin had become near normal in all the cases of autosomal recessive congenital ichthyosis. Remarkable reduction in stiffness was also observed in all children. Supplementation with high-dose vitamin D followed by recommended daily allowance appears to be an effective form of therapy in the management of congenital ichthyosis with vitamin D deficiency.

Digital Paper Prints as Replacement for LASER Films: A Study of Intra-Observer Agreement for Wrist Radiographic Findings in Rickets.

Replacement of conventional LASER films with digital paper prints as supplement to radiology reports may serve as an economical and environment friendly method. However, it is essential that such a change does not compromise patient's intended diagnostic outcome. The aim of this study was to assess the reliability and acceptability of digital paper prints for the radiographic images by the treating physicians and radiologists. This observational analytical study was done at a tertiary care hospital of New Delhi, India. A total of 58 consecutively ordered wrist radiographs of paediatric patients (6 months to 12 years of age) for ruling out rickets were retrieved from the PACS (Picture Archiving and Communication System). These 58 radiographs, out of which 21 (36.2%) had radiological evidence of rickets over PACS were printed on two different media i.e., LASER films and glossy photographic paper. An objective scoring for the severity of rickets was done on both LASER films and paper prints by six observers independently. Overall comfort level with paper prints was rated on a 1-5 point Likert scale. Data was analysed using STATA 14.0 (Stata Corp, College Station, TX). Intra-observer percentage agreement and value of Cohen's kappa for PACS vs. LASER films and PACS vs. paper prints was equal i.e., 98.3% and 0.97, respectively. Intra-observer agreement between LASER films and paper prints for all six observers was excellent, ranging from 0.92 to 1.00; percentage agreement ranging from 94.8% to 100%. Fracture of ulna/radius present in 4 sets of the X-rays was well demonstrated in both LASER films and paper prints. Comfort level with paper prints was rated as 5 out of 5 by all due to no requirement of any special illuminated view box and dark room. This study concludes that the use of paper prints may serve as a reliable alternative to LASER films to communicate the report of wrist radiographs for the treating physicians without any compromise over diagnostic information in cases of rickets.

Threshold levels of 25-hydroxyvitamin D and parathyroid hormone for impaired bone health in children with congenital ichthyosis and type IV and V skin.

Patients with congenital ichthyosis, especially those with darker skin types, are at increased risk of developing vitamin D deficiency and rickets. The relationships between 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH) and bone health have not been studied previously, in ichthyosis. To determine the threshold levels of 25(OH)D and PTH for impaired bone health in children with congenital ichthyosis. In this cross-sectional study, 119 children with ichthyosis and 168 controls were recruited. Serum 25(OH)D, PTH, calcium, phosphate and alkaline phosphatase (ALP) were measured. Radiological screening for rickets was carried out only in children with ichthyosis. Forty-seven children with ichthyosis had either clinical or radiological evidence of rickets. The correlation between serum 25(OH)D and PTH showed that a serum level of 25(OH)D 8ngmL(-1) was associated with a significant increase in PTH. The correlation between PTH and ALP showed that a serum PTH level of 75pgmL(-1) was associated with a significant increase in ALP levels. Of the different clinical phenotypes of ichthyosis, both autosomal recessive congenital ichthyosis (ARCI) and epidermolytic ichthyosis (EI) were found to have significantly increased PTH, ALP and radiological rickets scores compared with common ichthyosis. Serum levels of 25(OH)D≤8ngmL(-1) and PTH ≥75pgmL(-1) significantly increases the risk for development of rickets [odds ratio (OR) 2·8; 95% confidence interval (CI) 1·05-7·40; P=0·04] in ichthyosis. Among the different types, patients with ARCI (OR 4·83; 95% CI 1·74-13·45; P<0·01) and EI (OR 5·71; 95% CI 1·74-18·79; P<0·01) are at an increased risk of developing rickets.

Novel SLC34A3 mutation causing mild hypophosphataemia, hypercalciuria and nephrolithiasis but no clinical or radiological evidence of rickets

Novel SLC34A3 mutation causing mild hypophosphataemia, hypercalciuria and nephrolithiasis but no clinical or radiological evidence of rickets

Novel SLC34A3 mutation causing mild hypophosphataemia, hypercalciuria and nephrolithiasis but no clinical or radiological evidence of rickets

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Radiological Evidence of Rickets in a Lithuanian Child Mummy

This report concerns a female child mummy ([Fig. 1]) discovered in the Dominican Church of the Holy Spirit, Vilnius, Lithuania. The church stands over a number of subterranean chambers holding mummified human remains most likely dating from the 18th – 19th century AD.

Calcium and vitamin d requirements of enterally fed preterm infants.

Bone health is a critical concern in managing preterm infants. Key nutrients of importance are calcium, vitamin D, and phosphorus. Although human milk is critical for the health of preterm infants, it is low in these nutrients relative to the needs of the infants during growth. Strategies should be in place to fortify human milk for preterm infants with birth weight <1800 to 2000 g and to ensure adequate mineral intake during hospitalization and after hospital discharge. Biochemical monitoring of very low birth weight infants should be performed during their hospitalization. Vitamin D should be provided at 200 to 400 IU/day both during hospitalization and after discharge from the hospital. Infants with radiologic evidence of rickets should have efforts made to maximize calcium and phosphorus intake by using available commercial products and, if needed, direct supplementation with these minerals.

Oral calcium supplementation reverses the biochemical pattern of parathyroid hormone resistance in underprivileged Indian toddlers

Background:Toddlers in Pune, India, accustomed to low dietary calcium intake but vitamin D replete have low serum ionised calcium and inappropriately raised serum inorganic phosphorus concentrations together with elevated serum...

High frequencies of elevated alkaline phosphatase activity and rickets exist in extremely low birth weight infants despite current nutritional support

BackgroundOsteopenia and rickets are common among extremely low birth weight infants (ELBW, <1000 g birth weight) despite current practices of vitamin and mineral supplementation. Few data are available evaluating the usual course of markers of mineral status in this population. Our objectives in this study were to determine the relationship between birth weight (BW) and peak serum alkaline phosphatase activity (P-APA) in ELBW infants and evaluate our experience with the diagnosis of rickets in these infants.MethodsWe evaluated all ELBW infants admitted to Texas Children's Hospital NICU in 2006 and 2007. Of 211 admissions, we excluded 98 patients who were admitted at >30 days of age or did not survive/stay for >6 weeks. Bone radiographs obtained in 32 infants were reviewed by a radiologist masked to laboratory values.ResultsIn this cohort of 113 infants, P-APA was found to have a significant inverse relationship with BW, gestational age and serum phosphorus. In paired comparisons, P-APA of infants <600 g (957 ± 346 IU/L, n = 20) and infants 600–800 g (808 ± 323 IU/L, n = 43) were both significantly higher than P-APA of infants 800–1000 g (615 ± 252 IU/L, n = 50), p < 0.01. Thirty-two patients had radiographic evaluation for evidence of rickets, based on P-APA greater than 800 IU/L, parenteral nutrition greater than 3 to 4 weeks, or clinical suspicion. Of these, 18 showed radiologic rickets and 14 showed osteopenia without rickets. Infants with BW <600 g were more likely to have radiologic rickets (10/20 infants) compared to those with BW 600–800 g (6/43 infants) and BW 800–1000 g (2/50 infants), p < 0.01 for each. P-APA was not significantly higher in infants with radiologic rickets (1078 ± 356 IU/L) compared to those without radiologic evidence of rickets (943 ± 346, p = 0.18).ConclusionElevation of P-APA >600 IU/L was very common in ELBW infants. BW was significantly inversely related to both P-APA and radiologic rickets. No single value of P-APA was related to radiological findings of rickets. Given the very high risk of osteopenia and rickets among ELBW infants, we recommend consideration of early screening and early mineral supplementation, especially among infants <600 g BW.

Ichthyosiform erythroderma with rickets: report of five cases

We describe five children with ichthyosis and rickets. The association of ichthyosis and rickets is very rare. Four children had lamellar ichthyosis and one child had nonbullous ichthyosiform erythroderma/psoriasis with atopy. All had biochemical and radiological evidence of rickets. Three had clinically evident rickets, of whom two had very severe skeletal deformities. Such a severe skeletal involvement due to rickets in association with ichthyosis is exceptionally rare. We suggest that children with severe ichthyosis, in particular those with pigmented skin, need to be evaluated for rickets, especially in developing countries where there is a background prevalence of vitamin D deficiency.

Presentation of vitamin D deficiency

Aims: To describe the various ways in which vitamin D deficiency presents in children in selected districts of London and to identify which factors, if any, determine the mode of...

Nutritional vitamin D deficiency rickets in Sudanese children.

Nutritional vitamin D deficiency rickets was established in 41 Sudanese children aged from 3 months to 7 years by clinical, radiological and therapeutic response supported by biochemical investigations. There were 25 boys and 16 girls, of whom 42% were infants of less than 1 year. Forty-seven per cent of rachitic children were underweight. Six infants had early rickets with no bony swellings but had other clinical features and radiological evidence of rickets. One of them, aged 3 months, presented with hypocalcaemic convulsions. Three children had icthyosis. Serum alkaline phosphatase was raised in 75%, hypophosphataemia occurred in 68% and hypocalcaemia in 54% of patients. Anaemia, mostly hypochromic, was detected in 79%. Possible causes were poor socio-economic background, inadequate dietary intake in both mothers and children, prolonged breastfeeding, prematurity, limited sun exposure and type of residence. Nutritional vitamin D deficiency rickets should be looked for in Sudanese children, especially in preterms and in those living in flats.

X-linked hypophosphatemic mice: IGF-1 levels and plasma activity on in vitro renal Pi transport

A 5-year-old boy was found to have severe rickets in association with hyperpigmented, linear, verrucous, epidermal tumors, typical of the epidermal nevas syndrome. Normocalcemia (9.6 mg/dl), hypophosphatemia (2.0 mg/dl), elevated serun alkaline phosphatase concentration (313 IU), decreased renal tubular reabsorption of phosphorus (35%), radiologic evidence of rickets, and lack of response to usual therapeutic doses of vitamin D suggested hypophosphatemic vitamin D-resistant rickets. Therapy with vitamin D in doses to 750,000 IU and oral phosphate, 2.0 gm/day, failed to induce healing of the rickets. A subtotal parathyroidectomy performed when the patient was 9 years old was also without effect. When he was 12 years old several fibroangiomas on the face and left lower limb were excised. Within three months all biochemical abnormalities resolved and radiologic evidence of healing was observed. A portion of excised tissue was homogenized and injection of the supermate into a 6-week-old puppy induced excessive phosphaturia. The data suggest that the rickets was induced by a phosphaturic substance extractable from the tumors.

Convulsions as a Possible Manifestation of Vitamin D Deficiency Rickets in Infants One to Six Months of Age

During the 42 months of January 1985 through June 1988, five infants between the ages of one and six months had hypocalcemic convulsions associated with vitamin D deficiency rickets. Despite abundant sunlight, convulsions as a manifestation of vitamin D deficiency in young infants are not uncommon in Saudi Arabia and should be considered as a probable cause for hypocalcemic seizure in breast fed infants.

Bone mineral density of the spine and radius shaft in children with X-linked hypophosphatemic rickets (XLH)

X-linked hypophosphatemic rickets (XLH) is characterized by inadequate skeletal mineralization. The bone mineral density (BMD) of the radius shaft and the lumbar spine was determined in 13 children with XLH. Ten patients were on treatment, whereas three patients had discontinued treatment 20–32 months prior to this study. Two of them had radiological evidence of rickets. The radius shaft BMD was significantly diminished: Z score was −1.33 ± 0.89 ( P < 0.001), while the BMD of lumbar spine was significantly augmented ( Z score + 1.95 ± 1.17, P < 0.001). A positive correlation was found between the Z scores for the BMD of the radius shaft and spine. The two patients with overt rickets had lower radius shaft BMD values and a lesser increment of BMD of the spine. The BMD deficit of cortical bone may be related to the lack of efficacy of the treatment and/or to an intrinsic defect of the bone on this disease. On the other hand, the augmented BMD of the lumbar spine might reflect the overabundance of partially mineralized osteoid. The determination of the BMD of the radius shaft by SPA was a sensitive method for detecting abnormalities of the bone mass in XLH patients under treatment without radiological signs of rickets.

Calcium absorption in bone disease associated with chronic cholestasis during childhood

Fractional absorption of calcium was determined in 9 children aged 4.9 to 16.9 yr with chronic cholestatic liver disease to determine the role of calcium malabsorption in the development of metabolic bone disease. Radiological evidence of rickets was absent in all patients, but bone density, measured by single beam photon absorptiometry of the distal radius, was reduced in eight of nine subjects. Serum calcium and phosphorus concentrations were normal in all except one subject. Serum 25-hydroxyvitamin D concentration was decreased compared with controls in only one of nine patients, but serum 1,25-dihydroxyvitamin D concentrations were diminished in seven of nine subjects. In all subjects, dietary calcium and phosphorus intakes were greater than 80% of the RDA. Fractional absorption of calcium, determined by oral and intravenous administration of stable calcium isotopes, was similar in cholestatic compared with control subjects (37.1% +/- 12.5% vs. 34.0% +/- 16.4%). In the cholestatic subjects, calcium absorption correlated with serum 1,25-dihydroxyvitamin D (r = 0.871, p less than 0.002) but not 25-hydroxyvitamin D concentrations. Calcium balance, assessed by the duplicate diet method, was positive in four of five subjects. Anthropometric measurements were performed to examine the relationship between nutritional status and bone mineral content. Heights of all subjects were less than or equal to the 10th percentile and fat stores and somatic protein stores were less than the 25th percentile in six of nine subjects. We conclude that factors other than calcium malabsorption and decreased serum 25-hydroxyvitamin D concentration contribute to diminished bone mass in children with cholestatic liver disease.