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ECG tracing performed after admission, showing a normal sinusal rhythm with a prolonged QTc interval of 500 msec.
Source publication
Clinical manifestations of vitamin D deficiency rickets are widely described; however cardiorespiratory arrest is an extremely rare presentation.
The aim of this paper is to present the symptoms of severe vitamin D deficiency rickets and to highlight the importance of vitamin D prophylaxis in infants.
We report a case of a 16-month-old infant who p...
Context in source publication
Context 1
... ickets as a result is now of a vitamin rare disease D supplementation in industrialized during countries the first year of life and also wide availability of fortified food. However, cases of vitamin D deficiency rickets are still reported, especially among an immigrant population. A 16-month-old, dark-skinned infant initially presented to the emergency room with a stridor that was misdiag- nosed as viral laryngitis. After discharge from the emergency room, the stridor persisted until he presented a cardiorespiratory arrest 2 wk later. He was then successfully resuscitated by a mobile medical team and admitted to the hospital. The electrocardiogram (ECG) during resuscitation showed asystole. Immediately after resuscitation, he had lactic metabolic acidosis (pH 6.79; lactate, 14 mmol/ liter; pCO 2 , 32.3 mm Hg; bicarbonate, 5.1 mmol/liter) and hypocalcemia (ionized calcium, 0.42 mmol/liter; reference values, 1.1–1.5 mmol/liter; and total calcium, 1.15 mmol/liter; reference values, 2.15–2.55 mmol/liter). He made a full recovery with no neurological sequellae. There were no other obvious causes for his cardiopul- monary arrest. Cardiac ultrasound was normal. ECG tracing after admission (Fig. 1) showed a normal sinus rhythm but a prolonged QTc interval (calculated using Bazett’s correction) of 500 msec, which was resolved after the correction of hypocalcemia. Electroencepha- logram was normal. Laryngeal endoscopy showed mild edema with no malformation. Further questioning and investigation revealed that the infant was exclusively breastfed without vitamin D supplementation until 10 months of age. His mother did not receive any vitamin D supplementation either. He also ate or drank a minimal amount of dairy products. Physical exam revealed frontal bossing, widening of the wrists and ankles, prominence of the costochondral junctions, and hypotonia. Laboratory investigation showed the follow- ing: alkaline phosphatase, 1300 U/liter; reference values, 42–362 U/liter; serum phosphorous, 1.2 mmol/liter; reference values, 1.1–2 mmol/liter; 25-hydroxycholecalcif- erol, 5.7 g/liter; reference values, 30 –70 g/liter; urine calcium/creatinine ratio, 0.35 mol/mol; reference values, less than 0.75 mol/mol; and intact PTH, 325 ng/liter; reference values, 10 –70 ng/liter. The radiography of the wrist (Fig. 2A) showed evidence of cupping, fraying, metaphyseal widening, and demineralization of the distal radial and ulnar metaphyses. The bone mineral density of the lumbar spine measured by dual x-ray absorptiometry was 0.298 g/cm 2 , corresponding to a Z-score ( SD from the mean) below Ϫ 2 SD , calculated by using the data published by Salle et al. (1). He was then diagnosed with severe stage III rickets and treated with calcium gluconate 800 mg/d and vitamin D 4000 IU/d. After 3 months of treatment, the clinical signs markedly improved, together with a normal- ization of his 25-hydroxycholecalciferol level (Fig. 3), as well as all other laboratory values. He had no recurrence of stridor, and follow-up radiographs of the wrist (Fig. 2B) showed bone healing with an extensive periosteal new bone formation as a reflection of ossification of provisional zone of calcification and a marked ossification of radial and humeral epiphysis. Symptomatic vitamin D deficiency rickets is more fre- quently reported in infancy and adolescence than in childhood. This is due to the increased calcium demand secondary to the rapid growth velocity during these two periods. In infants and small children, the features of vi- tamin D deficiency include lethargy, bone deformities, re- current respiratory infections, stridor, tetany, and convul- sions (2– 4). Hypocalcemia secondary to vitamin D deficiency may also reduce myocardial contractility and lead to arrhythmias and left ventricular failure, as recently reported. Maiya et al . (5) describe 16 children with rickets and associated heart failure in the southeast of the United Kingdom. In all of them, hypocalcemia and vitamin D deficiency was suggested as the main cause of their car- diomyopathy. In contrast, our patient had normal echo- cardiography, ruling out a severe heart problem as a cause of his cardiac arrest. We cannot rule out that his severe hypocalcemia provoked a sudden heart arrhythmia with subsequent cardiac arrest (6). Our patient had multiple risk factors for the develop- ment of severe vitamin D deficiency rickets: he was dark- skinned, with poor sun exposure, exclusively breastfed without vitamin D supplementation, and eventually was given rice milk with no vitamin D or calcium supplements. He initially presented with stridor, which was (the fa- mous retrospectoscope!) a cardinal symptom of hypocal- cemic laryngospasm that was mistakenly taken for a viral laryngitis. A careful dietary history would have given ad- ditional clues to his final diagnosis. Hypocalcemic stridor related to nutritional rickets is not uncommon in infancy (2, 7, 8, 9), sometimes leading to apnea (10). The other causes of stridor were ruled out in our patient. Cardiorespiratory arrest caused by severe hypocalcemia secondary to vitamin D deficiency rickets is rare. We are aware of only one another case report (11). In analogy to our case, Holick et al. (12) recently reported a 9-month-old infant admitted with generalized seizure secondary to hypocalcemia due to severe vitamin D deficiency rickets as a result of being solely breast fed, with no vitamin D supplementation of either the infant or his mother. This infant was also dark-skinned, which put him more at risk of vitamin D deficiency rickets, as was our case. In conclusion, severe nutritional rickets is still present, especially in ethnic minorities with different dietary and lifestyle habits that put them at risk. Related symptoms of vitamin D deficiency rickets can be very mild, or, as in our case, extremely severe with stridor, laryngospasm, and subsequently cardiorespiratory arrest. A full (dietary) history should raise the suspicion of nutritional rickets in these cases, suspicion that will be confirmed with simple laboratory exams. There is a need for continuing vitamin D supplementation, especially in light of the new recommendation of the Insti- tute of Medicine ...
Citations
... The meta-analysis of all the studies (irrespective of study design and calcium intake) showed that children with rickets had a mean serum 25OHD of 23 nmol/L (N studies = 77, 95% CI [19][20][21][22][23][24][25][26][27], whereas children without rickets had a mean serum 25OHD of 62 nmol/L (N studies = 19, 95% CI [55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70]. When restricting the meta-analysis to case-control studies (N studies = 16), the children with and without rickets had a mean serum 25OHD of 32 (95% CI 23-40) nmol/L and 64 nmol/L (95% CI 56-73) nmol/L, respectively. ...
Purpose
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.
Conclusion
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.
... Rickets and osteomalacia are associated with a disturbed mineralization of the bone matrix, which leads to a softening of the bones. Rickets develops in children and typically causes growth retardation and bent legs [56][57][58]. Adults may be affected by a similar condition called osteomalacia, which causes muscle weakness and bone pain. Despite the fact that rickets and osteomalacia have a different etiology, they are usually caused by chronic hypophosphatemia. ...
FGF23 is a hormone secreted mainly by osteocytes and osteoblasts in bone. Its pivotal role concerns the maintenance of mineral ion homeostasis. It has been confirmed that phosphate and vitamin D metabolisms are related to the effect of FGF23 and its excess or deficiency leads to various hereditary diseases. Multiple studies have shown that FGF23 level increases in the very early stages of chronic kidney disease (CKD), and its concentration may also be highly associated with cardiac complications. The present review is limited to some of the most important aspects of calcium and phosphate metabolism. It discusses the role of FGF23, which is considered an early and sensitive marker for CKD-related bone disease but also as a novel and potent cardiovascular risk factor. Furthermore, this review gives particular attention to the reliability of FGF23 measurement and various confounding factors that may impact on the clinical utility of FGF23. Finally, this review elaborates on the clinical usefulness of FGF23 and evaluates whether FGF23 may be considered a therapeutic target.
... We compared the biochemical and echocardiographic parameters of the present cohort with those of previously published 27 patients with confirmed dilated cardiomyopathy due to vitamin D-deficient rickets (historical group). [12][13][14][18][19][20][21][22][23][24][25][26][27][28][29] ...
... 5,17,30 There are also case reports of dilated cardiomyopathy and cardiac failure in children, which recovered after vitamin D and calcium therapy. 10,13,14,[18][19][20][21][22]. ...
Objective
There are a few number of case reports and small-scale case series reporting dilated cardiomyopathy due to vitamin D-deficient rickets. The present study evaluates the clinical, biochemical, and echocardiographic features of neonates with vitamin D deficiency.
Patients and methods
In this prospective single-arm observational study, echocardiographic evaluation was performed on all patients before vitamin D3 and calcium replacement. Following remission of biochemical features of vitamin D deficiency, control echocardiography was performed. Biochemical and echocardiographic characteristics of the present cohort were compared with those of 27 previously published cases with dilated cardiomyopathy due to vitamin D deficiency.
Results
The study included 148 cases (95 males). In the echocardiographic evaluation, none of the patients had dilated cardiomyopathy. All of the mothers were also vitamin D deficient and treated accordingly. Comparison of patients with normocalcaemia and hypocalcaemia at presentation revealed no statistically significant difference between the ejection fraction and shortening fraction, while left ventricle end-diastolic diameter and left ventricle end-systolic diameter were higher in patients with hypocalcaemia. Previously published historical cases were older and had more severe biochemical features of vitamin D deficiency.
Conclusion
To the best of our knowledge, in this first and largest cohort of neonates with vitamin D deficiency, we did not detect dilated cardiomyopathy. Early recognition and detection before developing actual rickets and preventing prolonged hypocalcaemia are critically important to alleviate cardiac complications.
... Importantly, rickets is still a worldwide public health problem causing morbidity and mortality and is even increasing in Europe with immigrants from Middle East, Africa and Asia being at particularly high risk (174). Prevalence and incidence of vitamin D deficiencyassociated nutritional rickets is difficult to assess due to incomplete reporting and inconsistent case definition, but even if conservative estimates of only a few singledigit cases per 100,000 is true, vitamin D-deficient rickets and the therewith associated infant deaths are preventable and require adequate public health actions (174,175,176,177). ...
... The clinical morbidity associated with nutritional rickets includes impaired linear growth, chest wall deformity predisposing to pneumonia, fractures, bone pain, leg deformities with resultant disability, developmental delay of gross motor skills, and potentially lethal outcomes like hypocalcemic seizures, cardiomyopathy, and cardiac arrest. [77][78][79][80][81] Biochemical features of nutritional rickets include an elevated ALP, low serum phosphorus and calcium, and elevated PTH. Of these biomarkers, elevated ALP is the most sensitive biochemical feature, and in its absence, active rickets is unlikely. ...
... The clinical morbidity associated with nutritional rickets includes impaired linear growth, chest wall deformity pre-disposing to pneumonia, fractures, bone pain, leg deformities with resultant disability, developmental delay of gross motor skills, and potentially lethal outcomes like hypocalcemic seizures, cardiomyopathy, and cardiac arrest. [77][78][79][80][81] Biochemical features of nutritional rickets include an elevated ALP, low serum phosphorus and calcium, and elevated PTH. Of these biomarkers, elevated ALP is the most sensitive biochemical feature, and in its absence, active rickets is unlikely. ...
Vitamin D is an essential nutrient for bone health and may influence the risks of respiratory illness, adverse pregnancy outcomes, and chronic diseases of adulthood. Because many countries have a relatively low supply of foods rich in vitamin D and inadequate exposure to natural ultraviolet B (UVB) radiation from sunlight, an important proportion of the global population is at risk of vitamin D deficiency. There is general agreement that the minimum serum/plasma 25-hydroxyvitamin D concentration (25(OH)D) that protects against vitamin D deficiency-related bone disease is approximately 30 nmol/L; therefore, this threshold is suitable to define vitamin D deficiency in population surveys. However, efforts to assess the vitamin D status of populations in low- and middle-income countries have been hampered by limited availability of population-representative 25(OH)D data, particularly among population subgroups most vulnerable to the skeletal and potential extraskeletal consequences of low vitamin D status, namely exclusively breastfed infants, children, adolescents, pregnant and lactating women, and the elderly. In the absence of 25(OH)D data, identification of communities that would benefit from public health interventions to improve vitamin D status may require proxy indicators of the population risk of vitamin D deficiency, such as the prevalence of rickets or metrics of usual UVB exposure. If a high prevalence of vitamin D deficiency is identified (>20% prevalence of 25(OH)D < 30 nmol/L) or the risk for vitamin D deficiency is determined to be high based on proxy indicators (e.g., prevalence of rickets >1%), food fortification and/or targeted vitamin D supplementation policies can be implemented to reduce the burden of vitamin D deficiency-related conditions in vulnerable populations.
... 6,7 Our patient had no evidence of cardiomyopathy, and to our knowledge only 2 other cases of cardiac arrest without dilated cardiomyopathy have been described. 8,9 Vitamin D deficiency leading to hypocalcemic stridor is an infrequent presentation of rickets. Other children with rickets have developed stridor and laryngospasm. ...
... The authors of this report also underscore the strong possibility that medical diagnoses, including some of the diagnoses mentioned above, may have been/may be missed in alleged cases of shaken baby syndrome. One specific diagnosis that could explain both fractures and the triad is hypocalcemic vitamin D deficient rickets [44,45]. ...
Objective:
The objective of the present study was to review the histopathology in the original articles by authors Kleinman and Marks that described the specificity of the classical metaphyseal lesion for child abuse and to determine if there were any oversights in the authors' analysis.
Methods:
We reviewed the histopathology of the original studies that equated the classical metaphyseal lesion with child abuse. We compared this with the histopathology of metaphyseal fractures caused by known accidental, severe trauma in children and reviewed the histopathology of artifacts that can sometimes be produced in bone histology preparations.
Results:
Acute classical metaphyseal lesions showed no hemorrhage, and the chronic classical metaphyseal showed islands of cartilage proliferation at the metaphyses and growth plate, findings consistent with rickets and other metabolic bone disorders. Some of the acute metaphyseal lesions were consistent with artifacts.
Conclusion:
We believe the original studies that equate the classical metaphyseal lesion with child abuse are flawed. The most compelling observation that challenges the histopathology of the classical metaphyseal lesion as being a fracture is the absence of hemorrhage in the acute classical metaphyseal lesion. We hypothesize that some of the classical metaphyseal lesions were artifacts or represent metabolic bone disorders that were not considered and that these two non-traumatic explanations may have been the basis of the abnormal bone findings.
... Rickets is the most common form of metabolic bone disease in children and a cause of considerable disability. [1] Although rickets is now considered rare in developed countries due to vitamin D supplementation in infants and children, [2,3] it remains a problem in developing countries including those in sub-Saharan Africa. [4,7] Worldwide, the commonest cause of rickets in children is vitamin D deficiency due to inadequate sunlight and poor nutritional intake. ...
Vitamin D deficiency rickets has multiple aetiologiesin infants in the tropics and regions of abundant sunlight. The reduced intake of vitamin D frombreastmilk in mothers with vitamin D deficiency and absence of Vitamin D supplementation are common causes. Reports have shown vitamin D deficiency to be a rare underlying cause of rickets in Nigerian children a region with abundant sunlight. Here is a rare presentation of progressive painless wrist swelling in an 11months oldinfant with radiologic features and biochemical deficiency of Vitamin D in mother infant pair and marked reduction in sunlight exposure. Mother manifested features of possible osteomalacia in pregnancy, did not receive vitamin D supplements during pregnancy and after delivery, She also received little or no sunlight due to change in lifestyle as she stayed indoors with baby. This report therefore reveals risks factors for vitamin D deficiency in a region with abundant sunlight.
... 10 The severity of these symptoms may range from very mild to life threatening. 11 This case series discusses 3 examples of severe neonatal hypocalcemia, each with a complex course of disease. Although the clinical presentations were similar, the etiologies varied, and they therefore shed light on the complex differential diagnosis of hypocalcemia in neonates. ...
