Hypocalcemic Rickets Research Articles

A severe presentation of vitamin D-dependent hypocalcemic rickets associated with hypophosphatemia.

A severe presentation of vitamin D-dependent hypocalcemic rickets associated with hypophosphatemia.

A severe presentation of vitamin D-dependent hypocalcemic rickets associated with hypophosphatemia

A severe presentation of vitamin D-dependent hypocalcemic rickets associated with hypophosphatemia

PREVENTATIVE EFFECTS OF PROBIOTIC (MIACLOST) ON EXPERIMENTALLY INDUCED HYPOCALCEMIC RICKETS IN BROILER CHICKS.

A trial was conducted to study the effects of probiotic (Miaclost) supplement on experimentally induced hypocalcemic rickets in broiler chicks, a total of 180 one-day-old broiler chicks (Ross 308) were randomly divided into three equal groups 60 chicks per group with 3 replicates (20 birds /replicate) the dietary treatments consisted of a normal ration for G1, calcium-deficient ration 5% for G2 and calcium-deficient ration with addition of probiotics in drinking water for G3.Initial signs of rickets have been observed at 35-day of age in G2.while, in G1 and G3 no clinical signs observed, the gross lesions appeared enlargement of parathyroid gland, costochondral junction and increase in the width of growth plate of tibial bone of G2 whereas no gross lesions recorded in G1 and G3, the histopathological examination of parathyroid gland in G2 there were a focal parathyroid hyperplasia and increasing in numbers of syncytial cells and normal in G1 and G3, no intestinal histopathological changes in G1 and G2 and increase in height and width of the intestinal villi in probiotic group G3. Marked increase in the thickness of proliferation zone within growth plate of tibia bone in G2 and normal thickness in G1 and G3. the serum biochemical analysis of calcium of G2 recorded significantly low level in G2 and high level in G3 comparatively with G1, finally the serum alkaline phosphatase values were high significantly in G2 and normal in G3, it is concluded that probiotic (MiaClost) can be used as prophylaxis to prevent hypocalcemic rickets in broiler chicks

Vitamin D Deficiency Rickets in an Adolescent With Severe Atopic Dermatitis

Atopic dermatitis (AD) affects 10% to 20% of children worldwide. Its severity may be inversely correlated with 25-hydroxyvitamin D (25OHD) levels. Although low levels of vitamin D (VD) can cause rickets in infants, VD deficiency rickets is an unusual presentation in teenagers. We report the case of a 14-year-old girl with severe AD and fish allergy since early childhood. She lived at high latitude (with less sun exposure) and, because of her atopic disorders, avoided sunlight and fish. Laboratory studies showed elevated alkaline phosphatase and parathyroid hormone levels and low serum calcium; her serum 25OHD level was <12 nmol/L. A radiograph of the wrist showed a radiolucent band in the distal metaphysis of the radius with marginal sclerosis. She was diagnosed as having hypocalcemic rickets due to VD deficiency. Treatment with VD increased her 25OHD level to 44 nmol/L, with normalization of alkaline phosphatase, parathyroid hormone, and calcium. Moreover, we observed a dramatic improvement in her AD severity with VD treatment. This case demonstrates the complex interaction between VD deficiency, AD, and food allergy. We advise a high index of suspicion of VD deficiency rickets in children of all ages with AD, particularly during accelerated growth periods and in the presence of other risk factors such as darker skin, living at high latitude, sun avoidance, and low intake of VD-rich foods. The concomitant improvement in bone-related parameters and AD severity may reflect a double benefit of VD treatment, a possibility that warrants research on VD as potential treatment for AD.

Rickets: Twists and turns in the Gordian knot

Traditional scientific wisdom teaches that rickets, so plentiful in India, is caused by vitamin D deficiency and cured by vitamin D replacement. Rickets also occurs in the presence of vitamin D sufficiency, as in hypophosphatemic and hypocalcemic rickets; this, however, is not the topic of this editorial. It is still not understood why some children develop rickets, while others do not, even in the face of severe Vitamin D deficiency. This editorial tries to probe the recent twists and turns that researchers have taken while trying to unravel this Gordian knot.

Dilated cardiomyopathy due to hypocalcaemic rickets: is it always a reversible condition?

Nutritional rickets is still occasionally found in high-income countries, especially in populations at risk, and induced hypocalcaemia is a rare but possible cause of dilated cardiomyopathy. Although rare, physicians need to consider nutritional rickets in the differential diagnosis of hypocalcaemia cardiac failure, especially in high-risk populations such as immigrants. Despite being a reversible condition, the prognosis depends on the severity and time of diagnosis. We report two cases of exclusively breastfed infants with congestive cardiac failure due to hypokinetic dilated cardiomyopathy who had completely different outcomes. This report supports the need for prevention of this deficiency and underlies the role of vitamin D supplementation.

Rickets: prevalence of its forms and association with other pathological conditions in broiler chickens

The aim of this work was to perform a review of the bibliographic data regarding the spreading of rickets, as well as of its associations with certain pathological conditions in broiler chickens that had been exposed to rickets. The literature suggests that the occurrence of subclinical and clinical rickets within broiler flocks are a possible prerequisite for a number of pathological conditions such as femoral head necrosis (FHN), osteomyelitis, fractures, tibial dyschondroplasia (TD), vertebral column deformations with clinical expressions indistinguishable from spondylolisthesis, chronic respiratory disease (CCRD), ascites syndrome and other conditions related to morbidity within flocks. The gross lesions in the proximal tibiotarsus can be used for differentiation of clinical hypocalcaemic and hypophosphataemic rickets in broiler chickens. Macroscopically, hypocalcaemic rickets are hardly distinguished from tibial dyschondroplasia because the latter condition may be a consequence of the former in its etiological aspect.

Comparative pathomorphological study of rickets types in broiler chickens

The purpose of this study was to determine the incidence of rickets types in broiler chickens on the basis of gross and microscopic lesions in field clinical cases with regard to differential pathomorphological diagnosis.Clinical, serological, gross anatomy and histological investigations were carried out in broiler chickens with signs of rickets. The survey included 12 finisher broiler flocks (ten Ross 308 and two Cobb 500 flocks) from 4 different farms.Gross lesions in chickens from two of farms were indicative of hypophosphataemic rickets and the other two- of hypocalcaemic rickets types. Microscopic lesions correlated to macroscopic ones. The results of investigations showed that lesions resulting from calcium deficiency were very different from those occurring after phosphorus deficiency or calcium excess. It was suggested that macroscopic lesions in the proximal tibiotarsus could be used to distinguish field cases of Ca-deficiency and P-deficiency rickets in broiler chickens. The lesions in other leg parts (femur and tarsometatarsus) were not consistent with regard to differential diagnosis of rickets types due to the insufficient lesions in these bones.

Clinical and morphological investigations on the incidence of forms of rickets and their association with other pathological states in broiler chickens

The purpose of investigations was to determine, by means of pathomorphological methods, the incidence of different rickets forms and their role for the occurrence of other illnesses in broiler chickens in Bulgaria.Clinical, blood biochemical, gross anatomy and histological investigations were carried out in broiler chickens with signs of rickets. The studies were performed in 12 broiler flocks in 4 farms located in different regions of the country. Based on macro- and microscopic lesions, alterations specific for hypocalcaemic rickets were observed in two farms, whereas signs of hypophosphataemic rickets – in the other two. The rickets diagnosis was confirmed by analysis of blood serum calcium, magnesium and inorganic phosphate concentrations.At the age of 30–35days, various pathological states were observed in the same farms. The presented results suggested that existing problems in studied flocks were associated with an earlier occurrence of rickets.

Hypocalcemic Rickets and Dilated Cardiomyopathy: Case Reports and Review of Literature

Internationally, there have been isolated case reports published of children presenting with dilated cardiomyopathy (DCM) in the setting of undiagnosed rickets. Although there has been an increased prevalence of rickets in the United States, there has been only one documented case of associated DCM. At our institution, a hospital database search was conducted from year 1997 to year 2007 to identify patients with confirmed vitamin D deficiency in addition to DCM. Through this search, four exclusively breast-fed African American infants were identified. These infants presented with congestive heart failure secondary to DCM and, at their admission, were found to have laboratory evidence consistent with hypocalcemic rickets. These patients responded dramatically to treatment with vitamin D and calcium, and cardiac function returned to normal within months. Early recognition of vitamin D deficiency was an important factor in these patients' clinical course. These case reviews present a rare, serious complication of vitamin D-deficient rickets and support evidence for prevention of this nutritional deficiency with vitamin D supplementation in exclusively breast-fed infants.

Dietary effects on bone quality and turnover, and Ca and P metabolism in chickens

The responses of skeletal health and blood calcium (Ca) and phosphorus (P) status to different dietary calcium and available P (avP) contents were examined in 2-week-old chickens. High avP content resulted in more inorganic P (Pi) and less ionised Ca (Ca2+) in the blood. Birds on low Ca and high avP diets showed a higher incidence of tibial dyschondroplasia and hypocalcaemic rickets and were therefore assumed to be hypocalcaemic. However the molar Ca:P ratio in bone was closer to the expected 1·67:1 in diets high in avP. No significant dietary mineral content effect was found on bone mineral content, or breaking strength, within the range of diets used. Results suggest that variations in molar Ca:P ratios in bone have little effect on mechanical competence, and that diets for this strain should be higher in Ca, and could be lower in avP, than current recommendations.

Vitamin D resistance

This review will discuss the syndrome of hereditary hypocalcemic rickets due to generalized resistance to the action of the active vitamin D hormone, 1α,25-dihydroxyvitamin D. Historically, this entity usually has been refered to as “vitamin D–dependent rickets, type II” (VDDR II). However, now that the biochemical basis of the disease is understood, we prefer the terminology “hereditary vitamin D–resistant rickets” (HVDRR). In order to describe the syndrome of HVDRR, we will first briefly discuss the vitamin D endocrine system, the mechanism of action of 1,25(OH)2D, and the nature of the vitamin D receptor (VDR). After this background is presented, we will then portray the syndrome of HVDRR and detail the heterogeneous mutations in the VDR that cause the vitamin D–resistant state. Various aspects of vitamin D metabolism and action as well as the syndrome of HVDRR recently have been reviewed in the volume entitled Vitamin D(1).

Altered localisation of transforming growth factor-β3 during endochondral ossification in rachitic chicks

Growth plates from chicks displaying hypocalcaemic rickets, hypophosphataemic rickets and dyschondroplasia were studied. Immunohistochemical staining using specific TGF-β3 antibodies showed disruption of TGF-β3 localisation in all three disorders. In hypocalcaemic rickets, transitional and hypertrophic chondrocytes showed expression of TGF-β3, while accumulating, proliferative chondrocytes showed little expression. In the accumulating hypertrophic chondrocytes of hypophosphataemic rickets there was a reduction in the number of chondrocytes expressing TGF-β3, but transitional cells stained intensely. In the accumulating transitional chondrocytes of dyschondroplastic physes there was a reduction in the number of chondrocytes containing TGF-β3 and, in addition, the concentration of TGF-β3 appeared reduced. In all three disorders, there was localisation of some TGF-β3 in chondrocytes that appeared to be differentiating within the areas of repair. In addition, little TGF-β3 was detected in osteoclasts resorbing accumulated matrix from hypocalcaemic, hypophosphataemic and dyschondroplastic growth plates. These in vivo studies show a reduction in TGF-β3 localisation within growth plate chondrocytes and osteoclasts in three disorders in which chondrocytes cease to differentiate. This suggests that TGF-β3 may be important during chondrocyte differentiation in the growth plate.

Avian tibial dyschondroplasia: A comparison of the incidence and severity as assessed by gross examination and histopathology

The assessment of avian tibial dyschondroplasia ( td) in many recent studies is based on examination of slices of the proximal tibiotarsus with the naked eye. This study examines the incidence and severity of TD in broilers under four different dietary regimes and compares the efficacy of naked eye assessment with histopathological examination. The diets contained reduced levels of calcium relative to phosphorus with adequate (diet 1) and high (diet 2) levels of vitamin D3 supplementation; a very low calcium diet (diet 3) and a standard diet (diet 4) were also included. Gross examination suggested that TD was present in 80 per cent, 79 per cent and 27 per cent of tibiotarsi from birds on diets 1, 2 and 4, respectively. However, histological examination indicated TD, correspondingly, to be present in 18 per cent, 39 per cent and 6 per cent of tibiotarsi. Some birds on diet 1 exhibited physeal changes consistent with mild hypocalcaemic rickets. Many of the bone extremities which, grossly, were considered dyschondroplastic (diets 1, 2 and 4), histologically were shown to have an extensive hypertrophied zone with poor metaphyseal vessel penetration, but no cellular or matrix changes consistent with td. This cast doubt on the validity of earlier studies of td which relied solely on naked eye examination. The birds on diet 3 all demonstrated histopathology considered consistent with severe hypocalcaemic rickets and the present study suggests that in three-week-old broilers a moderately hypocalcaemic diet with a high level of vitamin D 3 will not cause rickets but will increase the incidence and severity of td. If the vitamin D 3 of the diet is reduced then a proportion of the proximal tibiotarsi will exhibit mild rachitic changes with a reduction in the incidence of td.

Comparative studies of type X collagen expression in normal and rachitic chicken epiphyseal cartilage.

The levels of type X collagen in mineralizing normal chicken epiphyses and nonmineralizing rachitic chicken tibial epiphyses were measured and compared. Qualitative immunoperoxidase studies with anti-chick type X collagen monoclonal antibodies on sections from normal and rachitic cartilage demonstrated that the type X collagen levels in rachitic growth plates are reduced. Northern hybridization of mRNA and biosynthetic studies have confirmed that type X collagen synthesis in rickets is also decreased. In hypocalcemic rickets, the level of type X collagen mRNA is reduced by 80% whereas the level of type X collagen mRNA is only reduced by 50% in normocalcemic rickets. These observations provide additional evidence that type X collagen is involved in the process of cartilage mineralization and also suggest that the partial recovery of type X collagen synthesis in normocalcemic rickets may be related to the elevated plasma concentration of calcium. Calcium concentration may therefore play an important role in the control of type X collagen synthesis.

Point mutations in the human vitamin D receptor gene associated with hypocalcemic rickets.

Hypocalcemic vitamin D-resistant rickets is a human genetic disease resulting from target organ resistance to the action of 1,25-dihydroxyvitamin D3. Two families with affected children homozygous for this autosomal recessive disorder were studied for abnormalities in the intracellular vitamin D receptor (VDR) and its gene. Although the receptor displays normal binding of 1,25-dihydroxyvitamin D3 hormone, VDR from affected family members has a decreased affinity for DNA. Genomic DNA isolated from these families was subjected to oligonucleotide-primed DNA amplification, and each of the nine exons encoding the receptor protein was sequenced for a genetic mutation. In each family, a different single nucleotide mutation was found in the DNA binding domain of the protein; one family near the tip of the first zinc finger (Gly----Asp) and one at the tip of the second zinc finger (Arg----Gly). The mutant residues were created in vitro by oligonucleotide directed point mutagenesis of wild-type VDR complementary DNA and this cDNA was transfected into COS-1 cells. The produced protein is biochemically indistinguishable from the receptor isolated from patients.

Clinical features of hereditary resistance to 1,25-dihydroxyvitamin D (hereditary hypocalcemic vitamin D resistant rickets type II).

In 1937 Albright and co-workers described a patient with hypophosphatemic rickets resistant to vitamin D therapy.1 They illustrated for the first time the concept that a state of hormone or vitamin deficiency could be caused by a defect in the tissue response to a factor rather than by reduced concentrations of that factor. In 1961 Prader and associates described a group of children with hypocalcemic rickets unresponsive to physiological doses of vitamin D (calciferol) but responsive to and dependent upon pharmacological doses of the vitamin.2 The terms pseudo-vitamin D deficiency or vitamin D dependency have been used interchangeably to describe this disorder.

Vitamin D-dependent rickets type I in pigs

We have bred a strain of pigs with an inherited condition of hypocalcaemic rickets, transmitted by an autosomal-recessive mechanism. Homozygous (affected) piglets grew at half the rate of their heterozygous (clinically normal) littermates, and developed profound hypocalcaemia with severe secondary hyperparathyroidism and hypophosphataemia by 8 weeks of age. In the hypocalcaemic piglets, plasma 1,25-dihydroxyvitamin D levels were low or undetectable, and 24,25-dihydroxyvitamin D3 levels were also reduced despite 25-hydroxyvitamin D3 levels being 2-fold higher. There was no detectable 25-hydroxyvitamin D3-1- or -24-hydroxylase enzyme activity in renal homogenates prepared from affected animals. Plasma and intestinal calcium-binding protein levels were reduced in the hypocalcaemic piglets. Sucrose density gradient analysis of intestinal cytosol, prepared in high-salt buffer, revealed the presence of a similar amount of a specific less than 4.2S 1,25-dihydroxyvitamin D3 binder in both groups of piglets. Administration of pharmacological doses of vitamin D3 to affected animals reversed the hypocalcaemia. We conclude that this strain of pigs has vitamin D-dependent rickets type I.

Endotoxin stimulated nitroblue-tetrazolium (NBT)-test in patients with hypoparathyroidism, pseudohypoparathyroidism and other forms of hypocalcemia

Endotoxin-stimulated NBT-tests were carried out in 15 patients with hypocalcemia of varying etiology and in 14 normocalcemic children free of infection. In the control group the formazan cell percentage (FCP) was 73.8 +/- 1.6% (range 63% to 83%). In 5 patients with hypoparathyroidism or pseudohypoparathyroidism the FCP before treatment was lower than normal. Vitamin D3 therapy produced a rapid increase of serum calcium but normalisation of NBT-test was only achieved after a latent period of one or more months. Patients with hypocalcemic rickets and children with an acute relapse of the nephrotic syndrome also showed abnormal results. The clinical significance of the NBT-test in hypocalcemic conditions is discussed.