Clinical and subclinical vitamin D deficiency in Bradford children.
A survey of the vitamin D status of Bradford schoolchildren was carried out in April 1973, employing conventional biochemistry, radiology, and measurement of 25-hydroxycholecalciferol levels. Biochemical evidence of rickets was present in 45% of the Asians. When re-examined in September, several children showed spontaneous biochemical resolution; nevertheless, radiological abnormalities were present in 12% of the original sample. No evidence of rickets was detected in the smaller White sample. Minor biochemical abnormalities were present in 9 of the 40 West Indian children. A study of admissions of Bradford hospitals in the 4 years 1969-1972 inclusive confirmed that clinical vitamin D deficiency was confined to Asians except for a few cases of infantile rickets in White children. The probability that one Asian child in 40 may require admission during the period from birth to adolescence emphasizes the urgent need for the introduction of prophylactic measures. (+info)
An inborn error of bile acid synthesis (3beta-hydroxy-delta5-C27-steroid dehydrogenase deficiency) presenting as malabsorption leading to rickets.
Deficiency of 3beta-hydroxy-delta5-C27-steroid dehydrogenase (3beta-HSDH), the enzyme that catalyses the second reaction in the principal pathway for the synthesis of bile acids, has been reported to present with prolonged neonatal jaundice with the biopsy features of neonatal hepatitis. It has also been shown to present between the ages of 4 and 46 months with jaundice, hepatosplenomegaly, and steatorrhoea (a clinical picture resembling progressive familial intrahepatic cholestasis). This paper reports two children with 3beta-HSDH deficiency who developed rickets during infancy and did not develop clinically evident liver disease until the age of 3 years. Bile acid replacement resulted in considerable clinical and biochemical improvement. The importance of thorough investigation of fat soluble vitamin deficiencies in infancy is emphasised. (+info)
Forgotten mysteries in the early history of vitamin D.
In the early 1920s, workers in both England and the US had discovered that rats on a rachitic diet would remain healthy if irradiated with ultraviolet light. However, they also found, to their surprise, that "control" rats too would recover if either their jar was irradiated without the rat in it or if a cage-mate was removed for irradiation and then returned. The ideas that either air or material objects that had been irradiated continued themselves to convey healthful secondary radiations were investigated but not confirmed. There was then the commercially important finding that with irradiation, some rachitic diets would become anti-rachitic. However, this effect did not explain all the previous findings. Consumption of either small irradiated fecal particles or of feces from irradiated rats was the likely explanation for the recovery of nonirradiated rats, but this was not tested by direct experiment, and it now appears unlikely that feces from irradiated rats would show significant antirachitic activity. It is suggested that an alternative possibility--activity of grease from irradiated fur--deserves investigation. (+info)
A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children.
BACKGROUND: Nutritional rickets remains prevalent in many tropical countries despite the fact that such countries have ample sunlight. Some postulate that a deficiency of dietary calcium, rather than vitamin D, is often responsible for rickets after infancy. METHODS: We enrolled 123 Nigerian children (median age, 46 months) with rickets in a randomized, double-blind, controlled trial of 24 weeks of treatment with vitamin D (600,000 U intramuscularly at enrollment and at 12 weeks), calcium (1000 mg daily), or a combination of vitamin D and calcium. We compared the calcium intake of the children at enrollment with that of control children without rickets who were matched for sex, age, and weight. We measured serum calcium and alkaline phosphatase and used a 10-point radiographic score to assess the response to treatment at 24 weeks. RESULTS: The daily dietary calcium intake was low in the children with rickets and the control children (median, 203 mg and 196 mg, respectively; P=0.64). Treatment produced a smaller increase in the mean (+/-SD) serum calcium concentration in the vitamin D group (from 7.8+/-0.8 mg per deciliter [2.0+/-0.2 mmol per liter] at base line to 8.3+/-0.7 mg per deciliter [2.1+/-0.2 mmol per liter] at 24 weeks) than in the calcium group (from 7.5+/-0.8 [1.9+/-0.2 mmol per liter] to 9.0+/-0.6 mg per deciliter [2.2+/-0.2 mmol per liter], P<0.001) or the combination-therapy group (from 7.7+/-1.0 [1.9+/-0.25 mmol per liter] to 9.1+/-0.6 mg per deciliter [2.3+/-0.2 mmol per liter], P<0.001). A greater proportion of children in the calcium and combination-therapy groups than in the vitamin D group reached the combined end point of a serum alkaline phosphatase concentration of 350 U per liter or less and radiographic evidence of nearly complete healing of rickets (61 percent, 58 percent, and 19 percent, respectively; P<0.001). CONCLUSIONS: Nigerian children with rickets have a low intake of calcium and have a better response to treatment with calcium alone or in combination with vitamin D than to treatment with vitamin D alone. (+info)
Enzymatic properties of human 25-hydroxyvitamin D3 1alpha-hydroxylase coexpression with adrenodoxin and NADPH-adrenodoxin reductase in Escherichia coli.
We have cloned human 25-hydroxyvitamin D3 1alpha-hydroxylase cDNAs from normal subjects and patients with pseudovitamin D-deficient rickets (PDDR), and expressed the cDNAs in Escherichia coli JM109 cells. Kinetic analysis of normal 1alpha-hydroxylase in the reconstituted system revealed that Km values for 25(OH)D3 and (24R), 25(OH)2D3 were 2.7 and 1.1 microM, respectively. The lower Km value and higher Vmax/Km value for (24R),25(OH)2D3 indicated that it is a better substrate than 25(OH)D3 for 1alpha-hydroxylase. These results are quite similar to those of mouse 1alpha-hydroxylase. To establish a highly sensitive in vivo system, 1alpha-hydroxylase, adrenodoxin and NADPH-adrenodoxin reductase were coexpressed in E. coli cells. The recombinant E. coli cells showed remarkably high 1alpha-hydroxylase activity, suggesting that the electrons were efficiently transferred from NADPH-adrenodoxin reductase through adrenodoxin to 1alpha-hydroxylase in E. coli cells. Using this system, the activities of four mutants of 1alpha-hydroxylase, R107H, G125E, R335P and P382S, derived from patients with PDDR were examined. Although no significant reduction in expression of these mutants was observed, none showed detectable activity. These results strongly suggest that the mutations found in the patients with PDDR completely abolished 1alpha-hydroxylase activity by replacement of one amino acid residue. (+info)
Demonstration of the rapid action of pure crystalline 1 alpha-hydroxy vitamin D3 and 1 alpha,25-dihydroxy vitamin D3 on intestinal calcium uptake.
The biological effects of crystalline 1alpha-hydroxyvitamin D3 and crystalline 1alpha,25-dihydroxyvitamin D3 have been compared on the intestinal uptake of calcium-45 by everted duodenal gut sacs from rachitic rats. Peak calcium-45 uptake was observed 1 hr after intravenous administration and both crystalline vitamin D2 analogs were of comparable potency. The rapid onset of calcium-45 uptake and the rapid attainment of maximal calcium-45 transport suggests a direct effect of these crystalline analogs on the mucosal membranes of the intestinal cell. (+info)
Malnutrition in infants receiving cult diets: a form of child abuse.
Severe nutritional disorders, including kwashiorkor, marasmus, and rickets, were seen in four children and were due to parental food faddism, which should perhaps be regarded as a form of child abuse. All disorders were corrected with more normal diets and vitamin supplements. In view of the potentially serious consequences of restricted diets being fed to children, families at risk should be identified and acceptable nutritional advice given. When children are found to be suffering from undernutrition due to parental food faddism a court order will normally be a necessary step in providing adequate treatment and supervision. (+info)
The function of vitamin D receptor in vitamin D action.
Vitamin D has roles in a variety of biological actions such as calcium homeostasis, cell proliferation and cell differentiation to many target tissues. Most of these biological actions of vitamin D are now considered to be exerted through the nuclear vitamin D receptor (VDR)-mediated control of target genes. VDR belongs to the nuclear hormone receptor superfamily and acts as a ligand-inducible transcription factor. For the ligand-induced transactivation of VDR, coactivator complexes have recently been shown to be essential. The function of VDR as a ligand-induced transcription factor is overviewed, and the phenotype of VDR gene knock-out mice and the VDR-mediated transcriptional and negative regulation of the key enzyme in vitamin D biosynthesis are also described, based mainly on our recent findings, to gain a better understanding of the function of VDR in the transcriptional control of vitamin D target genes. (+info)