PLASMA CONCENTRATIONS OF VITAMIN D METABOLITES IN A CASE OF RICKETS OF PREMATURITY

ABSTRACT. Rickets was diagnosed in an extremely low-birthweight infant 16 weeks after birth. She had a normal plasma concentration of 25-hydroxyvitamin D, a relatively low level of 24,25-dthy-droxyvitamin D, and a markedly elevated 1,25-dihydroxyvitamin D level compared with adult standards. The plasma concentrations of the vitamin D metabolites were, however, indistin-guishable from those of healthy preterm infants who received a similar diet of human milk and vitamins. The results indicate that rickets was not caused by vitamin D deficiency or by abnormal vitamin D metabolism, but by calcium and/or phosphate deficiency, and that the calcium and phosphorous content of human milk may be inappropriately low for very low-birthweight infants.     

Vitamin D-dependent rickets type II: extreme end organ resistance to 1,25-dihydroxy vitamin D3 in a patient without alopecia

Vitamin D-dependent rickets type II (VDDR II) is a rare syndrome resulting in severe rickets and is resistant to treatment with vitamin D and its derivatives. Patient with this disease, who are frequently the children of consanguinous marriages, present with elevated circulating concentrations of 1,25-dihydroxy vitamin D, the active metabolite of vitamin D, and in vitro studies have indicated a failure of intracellular binding of the hormone. Alopecia has been noted in many of these patients and it has been suggested that this feature may indicate a more marked resistance to treatment. However we describe a 3-year-old boy with this disease who, although having normal hair growth, displayed extreme resistance to treatment with active vitamin D metabolites. In vitro studies of skin fibroblasts disclosed not only an absence of hormone binding or 1,25(OH)₂D₃-induced 24-hydroxylase activity but reduced metabolism of 1,25(OH)₂D₃ itself. In this child, treatment with exogenous 1,25-dihydroxy vitamin D₃ at doses of up to 24g/day, which increased the circulating concentration of the metabolite to greater than 100 times the normal adult mean, failed to alleviate his condition and he died at the age of 39 months. This would therefore suggest that absence of alopecia, in this condition, cannot be regarded as a constant predictive sign of a lesser resistance and of responsivenes to Vitamin D treatment.Abbreviations VDDRII vitamin D-dependent rickets type II - AIK Phos alkaline phosphatase     

Serum 25-hydroxy-vitamin D levels in malnourished children with rickets.

Serum levels of calcium, phosphorus, alkaline phosphatase, and 25 hydroxy-vitamin D (25-OH-D3) were measured in normal and malnourished children with and without rickets. Children with rickets had clinical, biochemical, and x-ray evidence of the disease; most of them were malnourished. 25-OH-D3 levels were lower than in normal children. After treatment with vitamin D their condition improved. 25-OH-D3 levels were also found to be reduced in malnourished children without rickets. These studies show that rickets is common in malnourished children. Inadequate exposure to sunlight appears to be the factor mainly responsible for the high incidence of the disease. In addition, malnutrition perhaps contributes to the development of rickets.     

Rickets—not only the "English Disease"

ABSTRACT. Nutritional rickets in infancy and childhood due to vitamin D deficiency continues to be a world-wide problem. Its occurrence is probably higher in many tropical and sub-tropical countries, despite abundant sunlight than in many more northerly latitudes, where its incidence is mainly lited to children of Asian origin and those with dark skins. Social and cultural customs induding the adherence to a speaal, often vegetarian diet, the avoidance of sunlight together with increasing urbanisation, extended breast feeding and severe malnutrition are recognisable factors in the pathogenesis of rickets. Recent research has suggested that the regulation of vitamin D metabolism may be different in black children compared with those who have a fair skin. Supplementation of mothers in pregnancy and of children in infancy with vitamin D together with health education to promote a diet containing foods rich in vitamin D can ameliorate this preventable disease.     

Vitamin D Deficiency Rickets and Vitamin B12 Deficiency in Vegetarian Children

ABSTRACT. During the years 1978-83 four vegetarian children have been admitted to the pediatric departments of Ullevaal and Aker Hospitals in Oslo and Haukeland Hospital, Bergen, with the diagnosis of vitamin D deficiency rickets. One had vitamin B₁₂ deficiency as well. All had been fed a vegetarian diet with some cows'milk, but without vitamin supplementation. All had marked hypocalcemia, and three had tetany or convulsions. All responded well to conventional doses of vitamin D therapy. Two of the mothers had vitamin D deficiency, and one of them also had vitamin B₁₂ deficiency. This report describes the case histories of these children, and also discusses predisposing factors of vegetarian diets for the development of nutritional rickets     

佝偻病维生素D受体基因多态性与25-羟维生素D3相关性

目的：研究1~3岁佝偻病患儿中维生素D受体基因多态性FokⅠ位点与佝偻病相关性,初步探讨维生素D受体基因多态性FokⅠ位点在佝偻病发病中的作用。方法：病例组（佝偻病患儿）62例与对照组（正常健康儿童）60例,用ELISA方法检测血清25-羟维生素D3水平,比较两组之间血清25-羟维生素D3水平。用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测病例组和对照组维生素D受体基因多态性FokⅠ位点,比较两组之间基因型和等位基因分布频率。结果病例组血清25-羟维生素D3水平较对照组明显降低,差异有统计学意义（9.1±4.1 ng/mL vs 16.1±6.9 ng/mL;P＜0.05）。维生素D受体基因多态性FokⅠ位点病例组FF基因型明显高于对照组（53% vs 25%）,基因型分布频率差异有统计学意义（χ2=10.221,P＜0.05）,病例组F等位基因频率明显高于对照组（73% vs 57%）,等位基因分布频率差异有统计学意义（χ2=7.511,P＜0.05）。结论维生素D受体基因多态性FokⅠ位点与佝偻病有相关性,提示其在佝偻病遗传易感性方面起重要作用。［中国当代儿科杂志,2010,12（7）：544-546］     

维生素D缺乏性佝偻病遗传易感性的研究

目的：遗传因素是否参与维生素D缺乏性佝偻病目前尚未明了。拟通过研究维生素D受体基因多态性与维生素D缺乏性佝偻病易感性的相关性,探讨维生素D缺乏性佝偻病的遗传易感性。方法：应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术检测159例维生素D缺乏性佝偻病儿童和78例正常儿童(对照组)维生素D受体(VDR)基因FokI位点的多态性,比较两组之间VDR基因型和等位基因的频率。结果：维生素D缺乏性佝偻病患儿和对照组儿童的VDR基因FokI位点基因型分布频率分别为:FF(37%),Ff(51%),ff(12%)和FF(18%),Ff(55%),ff(27%),两组之间的差异有显著性(χ20.01(2)=9.210,χ2=13.3880,P<0.01);佝偻病患儿和对照组儿童的VDR基因FokI位点等位基因分布频率分别为:F(63%),f(37%)和F(46%),f(54%),两组之间的差异有显著性(χ2=6.18,P<0.05)。佝偻病患儿F等位基因分布频率明显高于对照组人群(63%vs46%)两组之间的差异有显著性;而佝偻病患儿f等位基因频率显著低于对照组(37%vs 54%)。结论：VDR基因FokI酶切位点的多态性可能与维生素D缺乏性佝偻病的遗传易感性有关。     

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.     

A Controlled Study on the Effect of Injected Water-Miscible Retinyl Palmitate on Plasma Concentrations of Retinol and Retinol-Binding Protein in Children with Measles in Northern Nigeria

ABSTRACT. Post-measles corneal ulceration resembling keratomalacia is frequently seen in young children in northern Nigeria. The concentration of retinol in plasma has been found to be depressed more by measles than by malnutrition. In order to determine whether this could be due to a specific influence of measles on the uptake, storage and release of retinol by the liver or its subsequent transport in the plasma, retinyl ester was administered parenteral^ to assess its effect on the concentration of circulating holo retinol-binding protein. A water-miscible preparation of retinyl palmitate was administered by intramuscular injection to well-and malnourished children with and without acute measles. In all cases, the concentration of both retinol and retinol-binding protein rose appreciably within 24 h of administration of the vitamin preparation. Thus the failure of post-measles corneal lesions to respond to orally or parenterally administered vitamin A would not appear to be due to the inability of such vitamin A to increase the level of circulating retinol in the plasma of children with measles.     

Serum levels of carboxyterminal propeptide of type I procollagen in healthy children from 1 st year of life to adulthood and in metabolic bone diseases

Type I collagen is the major component of bone matrix; circulating carboxyterminal propeptide of type I procollagen (P-I-CP) levels reflect type I collagen synthesis in tissues and may be an useful index to investigate bone metabolism. We measured P-I-CP by a new radioimmunoassay in 300 healthy children and adolescents and in 40 healthy adults to provide reference data for P-I-CP values. In addition, 79 patients with diagnosed disorders of phospho-calcium metabolism (rickets, vitamin D deficient and vitamin D resistant, hyperparathyroidism, hypo- and pseudo-hypoparathyroidism, osteopenia) were evaluated. In the healthy subjects, serum P-I-CP values were higher in children than in adults; variations of P-I-CP levels were observed according to age and sexual maturation: higher values were found in the first years of life and during pubertal development; pubertal increase reflects the different timing of pubertal development in the two sexes. P-I-CP levels were increased in primary hyperparathyroidism and reduced in diseases related to impaired secretion or action of parathyroid hormone. Higher P-I-CP levels were found in vitamin D deficient and vitamin D resistant rickets. P-I-CP was reduced in anorexia nervosa and during chronic glucocorticoid treatment while it was increased in thyrotoxic osteoporosis. In idiopathic juvenile osteoporosis, P-I-CP values ranged from reduced to increased values. We conclude that P-I-CP may represent an additional biochemical marker of bone metabolism. Since age-related variations are present, reference data for the various ages are need for clinical application of this assay.     

Vitamin D deficiency rickets and vitamin B12 deficiency in vegetarian children

During the years 1978-83 four vegetarian children have been admitted to the pediatric departments of Ullevaal and Aker Hospitals in Oslo and Haukeland Hospital, Bergen, with the diagnosis of vitamin D deficiency rickets. One had vitamin B12 deficiency as well. All had been fed a vegetarian diet with some cows' milk, but without vitamin supplementation. All had marked hypocalcemia, and three had tetany or convulsions. All responded well to conventional doses of vitamin D therapy. Two of the mothers had vitamin D deficiency, and one of them also had vitamin B12 deficiency. This report describes the case histories of these children, and also discusses predisposing factors of vegetarian diets for the development of nutritional rickets.     

A1c hemoglobin values in children with overt diabetes maintained in high degree of control

Studies of nine children 4 7/12 to 13 years of age who had rickets are presented. No evidence of renal abnormalities, vitamin D deficiency, or of the inherited varieties of rickets was found. The salient features were their rural origins, mild hypocalcemia with evidence of secondary hyperparathyroidism, and improvement with a normal diet that contained an average of 944 mg calcium/24 hours. It is proposed that the etiology of the rickets is related to low calcium intake with or without a high oxalate concentration in the diet.     

SERUM RETINOL-BINDING PROTEIN AND VITAMIN A LEVELS IN MALNOURISHED CHILDREN

Abstract. Reddy, V., Mohanram, M. and Raghuramulu, N. (National Institute of Nutrition, Hyderabad, India). Serum retinol-bindin protein and vitamin A levels in malnourished children. Acta Paediatr Scand 68: 65, 1979.—Serum levels of vitamin A and retinol-binding protein (RBP) were measured in children with vitamin A deficiency, in children with protein-energy malnutrition (PEM) and in normal children, before and after administration of 100000 IU of water-miscible vitamin A. Serum vitamin A and RBP levels were significantly low in children with vitamin A deficiency and in children with severe PEM, whereas the values in milder grades of PEM were similar to those of normal subjects. In severely malnourished children with corneal lesions, serum vitamin A concentration was reduced to a much greater extent than the level of serum RBP. Administration of vitamin A resulted in a significant increase in serum levels of both the components within 4 hours in all the 3 groups of children. The increase in RBP concentration observed in children with PEM was similar to that in vitamin A deficient children. These results indicate that in malnourished children, particularly in those who are at risk of developing keratomalacia, vitamin A is the main limiting factor. It is, therefore, recommended that children with PEM should be treated with vitamin A in addition to dietary protein and calories.     

Vitamin D prophylaxis in childhood]

The past 10 years have seen a return of rickets. Clinical and/or biochemical signs of vitamin D deficiency are still found in some children and adolescents, mainly during the winter. Sunlight exposure is able to prevent vitamin D deficiency and rickets but the dramatic influence of changes in solar ultraviolet-B radiation on cutaneous vitamin D3 synthesis, related to latitude and season effects, suggest that a vitamin D supplementation may be advisable. Moreover, human milk and common foods contain low quantities of vitamin D. So, we recommend routinely 400 IU of supplementary vitamin D per day in all infants. The vitamin D requirements in low-birth-weight infants are higher than at term infants; it is recommended the use of 1000-1600 IU per day in the first months of life. Intermittent high-dose of vitamin D and vitamin D metabolites are not advisable for prophylaxis of rickets.     

FAMILIAL HYPOPHOSPHATEMIC VITAMIN D RESISTANT RICKETS

Survey of all available data of infants with familial hypophosphatemia vitamin D resistant rickets observed partially or throughout the first year of life indicates that hypophosphatemia begins in the neonatal period regardless of whether or not the mother had been treated with vitamin D in high doses. Growth failure in vitamin D resistant rickets cannot be prevented even when treatment with high doses of vitamin D is begun early.     

Hypophosphatasia in a child with widened anterior fontanelle: lessons learned from late diagnosis and incorrect treatment

Hypophosphatasia is characterized by deficiency of serum alkaline phosphatase with defective bone and teeth mineralization. We report on an 11‐month‐old boy who developed a complex clinical picture characterized by bulging anterior fontanelle, growth failure, nephrocalcinosis and impaired bone mineralization during high‐dose calcium and vitamin D supplementation. This therapy had been started 5 months earlier for a presumed diagnosis of nutritional rickets established on the grounds of isolated widened anterior fontanelle. However, laboratory investigations revealed reduced alkaline phosphatase levels associated with hypercalcemia, hypercalciuria, low PTH and normal 25‐hydroxy vitamin D levels. Genetic testing detected a compound heterozygote for the novel mutation (c.262G>A) and the described mutation (c.920C>T) in the ALPL gene. Conclusion: High calcium and vitamin D supplementation should not be started in the presence of isolated signs of nutritional rickets without assessing calcium‐phosphate metabolism. In fact, in rare bone‐mineralizing disorders, this combined therapy might induce severe clinical complications.     

Metabolic studies in congenital vitamin D deficiency rickets

Congenital rickets in 3 newborns of mothers with advanced nutritional osteomalacia, healed with maternal breast milk feeding when mothers alone were given calcium supplements and 7.5 mg of intravenous D₂ and the mother baby pair protected from sunlight. Maternal plasma biochemistry indicated more severe vitamin D deficiency compared to their newborns (intrauterine foetal priority). The first dose of 7.5 mg of vitamin D₃ and calcium supplements to mother healed osteomalacia but did not appear to heal the rickets of their breast fed infants (extrauterine maternal priority for vitamin D). A second dose given at 3 months interval healed the rickets in their infants and the biochemistry of the mother and baby returned towards normal. Congenital rickets developed when maternal bone mineral and vitamin D stores had been completely exhausted. Raised IPTH levels in the newborn suggested that foetal parathyroids were responsive to hypocalcaemic stimulus.     

维生素 D 缺乏对子代大鼠肺形态结构及血小板源性生长因子-A 表达的影响

目的：研究孕期维生素 D（VitD）缺乏对子代大鼠肺形态发育及血小板源性生长因子-A（PDGF-A）表达的影响。方法：雌性Sprague-Dawley (SD) 大鼠随机分为对照组、VitD 缺乏模型组（每组6只）。对照组正常饲养;模型组予以避光、不含 VitD 的饲料喂养,2周后与成熟 SD 雄性大鼠交配,每组取孕20 d的胎肺及生后1 d 新生鼠肺,光镜及电镜下观察肺形态结构, RT-PCR 及 Western blot 分别检测肺组织PDGF-A mRNA及蛋白水平的表达。结果：光镜下,模型组子鼠肺泡平均表面积、平均呼吸膜周径均小于对照组（P<0.05）,平均肺泡间隔厚度大于对照组（P<0.05）;电镜下,模型组子鼠的板层小体数量明显少于对照组,成熟细胞器较少见。RT-PCR 及 Western blot结果显示模型组子鼠肺组织PDGF-A mRNA和蛋白表达水平均低于对照组（P<0.05）。结论：孕期 VitD 缺乏抑制孕晚期胎鼠及新生大鼠的肺形态发育。VitD 缺乏能显著抑制肺组织 PDGF-A 表达;PDGF-A表达减低可能是VitD缺乏抑制大鼠肺发育的重要机制之一。     

Serum concentrations of vitamin D metabolites in rachitic Libyan children

Twenty-two consecutive patients with rickets were studied in Benghazi, Libya. All were less than 2 years old. Rickets was associated with traditional cultural habits that limited sunshine exposure of the mothers and their infants, and with breast-feeding. Serum concentrations of the vitamin D metabolites 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D, and other parameters of mineral metabolism were typical of vitamin D deficiency disease, as was the biochemical and clinical response to treatment. Minimum safe serum levels of 25-OHD (20 nmol/L), and the serum levels of vitamin D metabolites in response to vitamin D treatment, were identical to previously obtained results from native Norwegian and Norwegian immigrant children with rickets, suggesting lack of racial differences in response to vitamin D. Fifty percent of the patients had adequate levels of vitamin D metabolites at the time of diagnosis, indicating that they had recently received oral vitamin D or cutaneous exposure to sunshine. Many cases of rickets in the area may, therefore, be spontaneously cured when the children's maturity allows adequate mobility and independence to achieve exposure to sunshine.     

Profile of rickets in hilly areas of himachal pradesh

Eighty four children of vitamin D deficiency rickets were studied. Most of the children belonged to families of poor socio-economic status and over half were malnourished. Thirteen infants aged 1 to 9 months presented with tetany, They had lower serum calcium (7.5 mg/dl) than patients with rickets but no tetany (serum calcium 8.4 to 9.8 mg/dl) Clinical features of hypocalcemia were also more marked and more common in patients with tetany. Important etiological factors were poor diet of the mothers, prevaling practices of rearing such as prolonged breast feeding without supplement and lack of exposure to sun due to excessive clothing to protect against the cold weather.