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     

Serum Concentrations of Vitamin D Metabolites in Exclusively Breast-Fed Infants at 70° North

ABSTRACT. The effect of prolonged breast-feeding on the serum concentrations of vitamin D metabolites, calcium, phosphate, and alkaline phosphatase was studied longitudinally in 7 infants from Northern Norway. They were exclusively breast-fed for a median of 71/2 months. Three of the mothers were supplemented with vitamin D throughout lactation. All but one of the infants had 25-hydroxyvitamin D (25-OHD) levels in the rachitic range (< 20 nmol/l) on at least one occasion. Vitamin D supplementation of the mother had no apparent effect on the infants' 25-OHD levels, but the values increased during summer. The infant who had the lowest 25-OHD levels also had decreased 1,25-dihydroxyvitamin D (1,25-(OH)₂D) concentrations, while the others maintained l,25-(OH)₂D levels within normal limits. 24,25-(OH)₂D concentrations were undetectable when the 25-OHD levels were below 35 nmol/l, but the two metabolites were closely correlated for higher values of 25-OHD. Low 25-OHD levels were associated with decreased phosphate concentrations at 6 months. The calcium levels were normal throughout the study period of one year, as were all but two of the alkaline phospatase values. Although none of the infants had clinical or biochemical evidence of rickets, the results suggest that the vitamin D supply from human milk is inadequate, and that routine vitamin D supplementation is advisable for breast-fed infants who are deprived of sunlight exposure.     

EFFECT OF SEASON AND VITAMIN D SUPPLEMENTATION ON PLASMA CONCENTRATIONS OF 25-HYDROXYVITAMIN D IN NORWEGIAN INFANTS

ABSTRACT. Plasma concentrations of 25-hydroxyvitamin D (250HD) were determined in 81 vitamin D supplemented or unsupplemented infants at the end of winter. The values were compared with maternal levels and with concentrations found in 22 unsupplemented infants at the end of summer. The 250HD levels of the neonates were lower, but closely related to maternal values ( r =0.95, p <0.0005). Unsupplemented breast-fed infants had lower 250HD levels at 6 weeks than at 4 days (16±7 vs. 32±15 nmol/l, mean ±1 SD, p <0.0005). The mean 250HD level of vitamin D supplemented 6-12 months old infants was intermediate between those of the unsupplemented nursed groups and the unsupplemented children studied during summer (53±28 vs. 85±28 nmol/l, p <0.0005). Six weeks old infants who had received a milk formula containing 400 IU vitamin D₃ per liter had levels similar to the latter group (92±21 nmol/l). The data suggest that the vitamin D stores acquired during fetal life, or from ultraviolet light exposure during the summer, may be inadequate to maintain safe levels of 250HD throughout the winter, but that a daily supplement of 400 IU is adequate to establish concentrations in the summer range.     

In vitro study of the giant tubule collagen formation in bovine dentin by [3H]- proline incorporation

Abstract – Unerupted permanent bovine incisors studied by routine autoradiography using radioactive proline incorporation revealed collagen formation within the giant tubules situated in the incisal dentin. A high [³H]-proline labeling was seen within the pulpal vascularized portion of the giant tubules, as well as in association with groups of cells immediately incisal to the blood vessel loops. The incisal portion of the giant tubules showed no or insignificant [³H] -proline labeling.     

Transmission electron microscopic study of giant tubules in bovine dentin

Abstract – Giant tubules in the axiomesiodistally extended incisal dentin of unerupted permanent bovine incisors from 1/2-11/2-yr-old calves were studied by TEM. The pulpal portion of each giant tubule contained two capillaries forming a loop incisally. The capillaries consisted of a delicate, continuous, or fenestrated endothelium and often had a pericyte coating. Cells with a rich RER, mitochondria, and Golgi apparatus dominated along and just incisal to the vessels. Extravasated erythrocytes and occasional macrophages were also seen in the latter location. It was suggested that the pulpal retraction of the giant tubule vessels during primary dentinogenesis might be the result of an intermittent sequestration of the most incisal portion of the loop, concomitant with endothelial proliferation in the pulpal portion of the capillaries. The major portion of the giant tubules, incisal to the vessels, contained a dense matrix of more or less axially oriented unmineralized 0.07–0.1-um-thick collagen fibrils and single cells showing gradually increasing degenerative and necrotic changes in an incisal direction. Longitudinal sections of the mineralized tubular walls revealed transversely cut collagen fibrils. The incisally located giant tubule origins were circumvented by dentinal tubules and contained 0.10–0.22-um-thick, densely packed collagen fibrils with an electron dense perifibrillar zone.     

Histochemical study of giant tubule content in dentin of unerupted cow incisors

Abstract – Incisal dentin of mandible cow incisors was studied by incident light. The material consisted of 12 intact permanent unerupted incisors from 2-yr-old cows removed immediately after bleeding. These specimens were kept in an isotonic EDTA-sucrose solution to be decalcified while maintaining vitality of cellular components. Three of the specimens were successfully dissected in a mesiodistal plane, exposing the giant tubule lumens and their content. By the use of NBT, a compound reduced by the dehydrogenase enzymes of the electron transport in the inner mitochondrial membrane, it was concluded that the giant tubules contained vital cells. The giant tubules were also shown to communicate with the incisal part of the pulp cavity by wide openings.     

VITAMIN D NUTRITIONAL STATUS OF PREMATURE INFANTS SUPPLEMENTED WITH 500 IU VITAMIN D2 PER DAY

ABSTRACT. The vitamin D nutritional status of premature infants was assessed by determining plasma 25-hydroxyvitamin D concentrations before and during supplementation with 500 IU vitamin D₂ per day. Fifty-one samples were collected from 25 healthy infants fed breast milk and a vitamin D₃ fortified formula. Gestational age was 32.2±2.4 weeks (mean ± 1 SD). 25-hydroxyvitamin D levels before supplementation correlated well with maternal values ( r =0.81). The infants' mean plasma concentration increased from 30.6±13.7 nmol/l (mean±1 SD) after birth to 46.3±10.5 nmol/l after 9±1 days ( p <0.0025), and to 65.3±16.6 nmol/l after 37±10 days of vitamin D₂ treatment ( p <0.0005). 25-hydroxyvitamin D₂ and 25-hydroxyvitamin D₃ were determined separately, and it appeared that the rise was accounted for by the D₂ fraction while 25-hydroxyvitamin D₃ concentrations were unchanged. The results demonstrate that vitamin D₂ is well absorbed and hydroxylated in the 25 position by premature infants free of associated disease, and that a supplementation of 500 IU per day in addition to breast milk and a regular vitamin D fortified formula is adequate to rapidly establish 25-hydroxyvitamin D levels within the normal adult range.     

Nephrocalcinosis, Hypercalciuria and Elevated Serum Levels of 1,25-Dihydroxyvitamin D in Children Possible Link to Vitamin D Toxicity

ABSTRACT. Ten children, age 1 1/2 to 14 years, had bilateral nephrocalcinosis and hypercalciuria, but normal serum calcium (Ca) and phosphate (P) concentrations. Patients with hypercalciuria were divided into absorptive (n=4) and renal (n=6) subgroups, and in the latter four patients had a primary Ca-leak and two had a P-leak. All the children had received intermittent high dose vitamin D prophylaxis during infancy. At the time of investigation all had normal serum levels of 25-hydroxyvitamin D, yet all but one had elevated values of 1, 25-(OH)₂D. Although the hypercalciuria was indistinguishable from the various known forms of idiopathic hypercalciuria, the previous clinical course and the pattern of bone mineral homeostasis suggest that both clinical features, namely nephrocalcinosis and hypercalciuria were related to vitamin D toxicity through various pathogenetic pathways.     

Plasma Concentrations of Vitamin D Metabolites before and during Treatment of Vitamin D Deficiency Rickets in Children

ABSTRACT. Plasma concentrations of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-(OH)₂D), and 24,25-dihydroxyvitamin D (24,25-(OH)₂D) were determined in 17 children with vitamin D deficiency rickets before therapy was started. Thirteen of them also had these tests repeated during treatment. The median 25-OHD concentration was at the lower limit of the reference range before, but increased distinctly within one week of treatment with 1700–4000 IU vitamin D per day (17 vs. 37 nmol/l, p < 0.01). 24,25-(OH)₂D was undetectable in twelve of the patients before therapy. Detectable concentrations were in the range of 1.7 to 3.5 % of the corresponding 25-OHD levels throughout the study, and the two metabolites were closely correlated ( r = 0.84, p < 0.0005). The median l,25-(OH)₂D concentration was near the average of the reference range before, but increased to well above the upper limit of normal within one week of treatment (121 vs. 368 pmol/l, p < 0.01). The levels were largely normal after 10 weeks of therapy, as were the plasma concentrations of calcium, phosphate, and alkaline phosphatase. Parathyroid activity, as judged by serum parathyroid hormone or urinary cyclic AMP concentrations, was stimulated in 11 of 12 children studied prior to treatment. It is concluded that there may be no clear-cut differences between normal nad rachitic values of the different vitamin D metabolites under practical clinical conditions. A low 25-OHD level combined with evidence of a stimulated parathyroid activity, and a rise of l,25-(OH)₂D levels to supernormal values following a few days of vitamin D therapy may be diagnostic clues.     

The Prevalence of Mutations in KCNQ1, KCNH2, and SCN5A in an Unselected National Cohort of Young Sudden Unexplained Death Cases

Introduction: Sudden unexplained death account for one‐third of all sudden natural deaths in the young (1–35 years). Hitherto, the prevalence of genopositive cases has primarily been based on deceased persons referred for postmortem genetic testing. These deaths potentially may represent the worst of cases, thus possibly overestimating the prevalence of potentially disease causing mutations in the 3 major long‐QT syndrome (LQTS) genes in the general population. We therefore wanted to investigate the prevalence of mutations in an unselected population of sudden unexplained deaths in a nationwide setting. Methods: DNA for genetic testing was available for 44 cases of sudden unexplained death in Denmark in the period 2000–2006 (equaling 33% of all cases of sudden unexplained death in the age group). KCNQ1, KCNH2, and SCN5A were sequenced and in vitro electrophysiological studies were performed on novel mutations. Results: In total, 5 of 44 cases (11%) carried a mutation in 1 of the 3 genes corresponding to 11% of all investigated cases (R190W KCNQ1, F29L KCNH2 (2 cases), P297S KCNH2 and P1177L SCN5A). P1177L SCN5A has not been reported before. In vitro electrophysiological studies of P1177L SCN5A revealed an increased sustained current suggesting a LQTS phenotype. Conclusion: In a nationwide setting, the genetic investigation of an unselected population of sudden unexplained death cases aged 1–35 years finds a lower than expected number of mutations compared to referred populations previously reported. We therefore conclude that the prevalence of mutations in the 3 major LQTS associated genes may not be as abundant as previously estimated. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1092‐1098, October 2012)