Deficiency rickets

The basic clinical tool used at the present time Is the competitive ligand binding assay for 25-OH-D. Although concentrations are low In the serum of patients with osteomalacia and v . tamln D deficiency rickets, we have recently noted the Interesting paradox that levels can be only 1/2 normal In the face of oyert bone disease (32). This had led us to propose that substrate levels of 25-OH-D3 available to the hydroxylase In kidney which Is responsible for the conversion of 25-OH-D3 to the tissue active metabolite, l,25(OH)2D3, may be rate limiting for this enzyme. 

The pharmacotherapeutic uses of vitamin D include vitamin D deficiencies, rickets in children and osteomalacia in adults, and renal osteodystrophy in patients with chronic renal failure. For metabolic rickets in patients with a deficiency of... 

Phosphate is critical to normal bone mineralization when phosphate stores are deficient, a clinical and pathologic picture resembling vitamin D-deficient rickets develops. However, affected children fail to respond to the usual doses of vitamin D used in the treatment of nutritional rickets. A defect in l,25(OH)2D production by the kidney has also been noted,... 

These distinctly different autosomal recessive diseases present as childhood rickets that do not respond to conventional doses of vitamin D. Type I vitamin D-dependent rickets, now known as pseudovitamin D deficiency rickets, is due to an isolated deficiency of l,25(OH)2D production caused by mutations in 25(OH)D-la-hydroxylase (CYP27B1). This condition... 

Phosphate is critical to normal bone mineralization when phosphate stores are deficient, a clinical and pathologic picture resembling vitamin D-deficient rickets develops. However, such children fail to respond to the usual doses of vitamin D employed in the treatment of nutritional rickets. A defect in l,25(OH)2D production by the kidney has also been noted, because the serum l,25(OH)2D levels tend to be low relative to the degree of hypophosphatemia observed. This combination of low serum phosphate and low or low-normal serum l,25(OH)2D provides the rationale for treating such patients with oral phosphate (1-3 g daily) and calcitriol (0.25-2 Mg daily). Reports of such combination therapy are encouraging in this otherwise debilitating disease. 

The site and type of bone deformity seen in rickets depend on the age of the child. In a small infant, deformities of the forearms and anterior bowing of the distal tibias are more common. Clinical features such as craniotabes (areas of thinning and softening in the bones of the skull), hypotonia, and tetany are common in vitamin D-deficiency rickets, which occurs more frequently in infants 1 year old or younger. These features may be absent in calcium-deficiency rickets, which usually presents after the age of 1 year or after the child has been... 

The biochemical features of calcium-deficiency and vitamin D deficiency are very similar. Both disorders result in a low-to-normal serum calcium concentration, an elevated PTH level, a decreased or normal phosphorus concentration, and increased alkaline phosphatase activity. The serum concentration of 25-hydroxyvitamin D is normal or slightly decreased in calcium-deficiency rickets but is markedly decreased in vitamin D deficiency. On the other hand, the serum concentration of 1,25-dihydroxyvitamin D is greatly elevated in calcium-deficiency rickets but is normal or even slightly decreased in vitamin D-deficiency rickets. 

Assume that you are a public health official in northern Nigeria. What actions might you take at the population level to reduce the risk and incidence of calcium-deficiency rickets in the region ... 

The fourth section deals with various aspects Digestion, Absorption, and Nutritional Biochemistry. The chapter Obesity considers current problems with respect to the ever-increasing incidence of imbalance between energy intake and utilization. Key problems of undemutrition are discussed in the chapters Protein-Energy Malnutrition and Vitamin A Deficiency in Children. The chapters Lactose Intolerance, Pancreatic Insufficiency, and Abetalipoproteinemia focus on the biochemical processes underlying food digestion and absorption. Calcium Deficiency Rickets, Vitamin B12 Deficiency, and Hemochromatosis provide discussions of absorption and utilization of vitamin D, vitamin B12, and iron, respectively. 

Vitamin D deficiency rickets, and osteomalacia tend to arise in several conditions or environments, as listed hereunder. Generally the combined lack of sunlight and dietary deficiency must exist before any sign of the deficiency arises. 

Binet, A., and Kooh,S. (1996). Persistence of vitamin D-deficiency rickets in Toronto in the 1990s. Can. J, Pubiic Health July-Aug., pp, 227-230. 

Wehinger H. Spatrachitis nach Vitamin-D-Uberempfindhchkeit bei Adiponekrosis subcutanea in der Neugeborenenperiode. [Vitamin D deficiency rickets after vitamin D hypersensitivity with subcutaneous fat necrosis in the newborn period.] Z Kinderheilkd 1969 107(l) 42-52. 

Dj la-hydroxylase gene in patients with pseudovitamin D-deficiency rickets. N. Engl. J. Med. 338, 653-661. 

S. Mylchreest, C.R. Paterson et al. (1999). Novel mutations in the la-hydroxylase (P450cl) gene in three families with pseudovitamin D-deficiency rickets resulting in loss of functional enzyme activity in blood-derived macrophages. J. Bone Miner. Res. 14, 730-739. 

Kitanaka, S., A. Murayama, T. Sakaki, K. Inouye, Y. Seino, S. Fukumoto et al. (1999). No enzyme activity of 25-hydroxyvitamin D la-hydroxylase gene product in pseudovitamin D deficiency rickets, including that with mild clinical manifestation. J. Clin. Endocrinol. Metab. 84, 4111 117. 

Dardenne, O., J. Prud homme, A. Arabian, FH. Glorieux, and R. St-Amaud (2001). Targeted inactivation of the 25-hydroxyvitamin Dj-la-hydroxylase gene (CYP27B1) creates an animal model of pseudovitamin D-deficiency rickets. Endocrinology 142, 3135-3141. 

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