Rickets hypophosphatemic

Chronic renal disease Hypophosphatemic vitamin D-resistant rickets Vitamin D-dependent rickets... 

Cho HY et al A clinical and molecular genetic study of hypophosphatemic rickets in children. Pediatr Res 2005 58 329. 

A human Na+/ P cotransporter in the kidney is also essential. An X-linked trait leading to inadequate synthesis of the transporter causes hypophosphatemic vitamin D-resistant rickets 499... 

X-linked hypophosphatemic rickets is characterized by defective proximal renal tubular phosphate transport and impaired renal production of 1,25-dihydroxycolecalci-ferol. These abnormalities lead to renal phosphate wasting, hypophosphatemia with normocalcemia, low plasma 1,25-dihydroxycolecalciferol concentrations, and... 

Anecdotal observations suggest that excessive use of oral phosphates may be a risk factor for the development of tertiary hyperparathyroidism in patients with X-linked hypophosphatemic rickets. Of 13 patients with X-linked hypophosphatemic rickets two developed tertiary hyperparathyroidism and 11 secondary hyperparathyroidism during treatment (939). Patients with tertiary hyperparathyroidism had on average earlier and longer treatment and higher doses of phosphates (over lOOmg/kg/day) than the 11 patients with secondary hyperparathyroidism. Those who later developed tertiary hyperparathyroidism had very high serum parathormone concentrations (over 42 pmol/1). 

Makitie O, Kooh SW, Sochett E. Prolonged high-dose phosphate treatment a risk factor for tertiary hyperparathyroidism in X-linked hypophosphatemic rickets. Clin Endocrinol 2003 58 163-8. 

Mis-localisation of annexin 2 has recently been implicated in the pathogenesis of Dent s disease. This term is now used collectively to describe what was previously four conditions that affect kidney function X-linked recessive nephrolithiasis with renal failure, X-linked recessive hypophosphatemic rickets, idiopathic low molecular weight proteinuria with hypercalciuria and nephrocalcinosis and Dent s disease. Patients with this condition present with low molecular weight proteinuria and hypercalciuria. Renal stones, nephrocalcinosis and renal failure are common late-stage developments. The condition has been attributed to abnormal acidification within endosomes of the proximal tubular cells. It is very rare and is usually caused by mutations in the voltage-dependent Cl /H+ chloride antiporter CLCN5, but occasionally in the PI4,5P2 5-phosphatase, OCRL1 (oculocerebrorenal syndrome of Lowe protein 1). 

Renal elimination of phosphorus is regulated by PTH, calcitriol, growth hormone, insulin, and insulin-like growth factors. While the above-mentioned hormones show a number of other effects, the existence of a hormone affecting selectively the extracellular concentration of phosphorus is expected. The task of this hormone with phosphaturic effect has been speculated about from the beginning of the 1990s. It was named phosphatonin, and its increased concentration is found especially in patients with osteomalacia (tumor-induced osteomalacia, X-linked hypophosphatemic rickets, epidermal nevus). The phosphaturic effect of... 

X-linked hypophosphatemic rickets is caused by abnormal reabsorption of phosphate in the proximal renal tubule, resulting in excessive excretion of phosphate and hence hypophosphatemia. There may also be blunting of the normal increase in calcidiol 1 -hydroxylase activity in response to hypophosphatemia. The gene responsible for the condition has been identified (the PHEX gene) its product is a membrane-bound endopeptidase that normally acts to clear the hormone phosphatonin from the circulation. Phosphatonin acts to decrease the activity of the sodium/phosphate cotransporter in the kidney (Drezner, 2000). 

Hypercalcemia persists for many months after the cessation of excessive intakes of vitamin D, because of the accumulation of the vitamin in adipose tissue and its slow release into the circulation. The introduction of calcitriol and 1 a -hydroxycalcidiol for the treatment of such conditions as hypoparathyroidism, renal osteodystrophy, hypophosphatemic osteomalacia, and vitamin D-dependent rickets has meant that hypercalcemia is less of a problem than when high doses of vitamin D were used in the treatment of these conditions. Because calcitriol has a short half-life in the circulation, the resultant hypercalcemia is of shorter duration than after cholecalciferol, and adjustment of the dose is easier. 

Foldes J, Balena R, Ho A, Parfitt AM, Kleerekoper M. Hypophosphatemic rickets with hypocalciuria following long-term treatment with aluminum-containing antacid. Bone 1991 12(2) 67-71. 

A child with X-linked hypophosphatemic rickets developed vitamin D intoxication during treatment with alfacalcidol and phosphorus. Besides the usual findings in this condition he had precocious synostosis of the skull, with signs of raised intracranial pressure. In view of earlier reports of coincidence of craniostenosis and X-linked hypophosphatemic rickets the authors pointed to the possibility that intoxication with alfacalcidol was the precipitating factor. In addition, hypersensitivity to alfacalcidol was found 2 months after the end of treatment, with normal concentrations of calcitriol (56). 

Carlsen NL, KrasUnikoff PA, Eiken M. Premature cranial synostosis in X-linked hypophosphatemic rickets possible precipitation by 1-alpha-OH-cholecalciferol intoxication. Acta Paediatr Scand 1984 73(l) 149-54. 

Oral phosphate administration leading to renal calcium phosphate precipitation has been described in children with X-linked hypophosphatemic rickets. Children with this condition are treated with oral phosphate and vitamin D and frequently developed ultrasonographic evidence of nephrocalcinosis, and the grade of nephrocalcinosis correlates with cumulative phosphate intake [46]. Renal biopsy findings are similar to those seen in acute phosphate nephropathy, with calcifications confined to tubules and the peritubular interstitium [47]. 

Verge CF, Lam A, Simpson JM, Cowell CT, Howard NJ,SilinkM. Effects of therapy in X-linked hypophosphatemic rickets. N Eng J Med 1991 325 1843-8. 

Alon U, Donaldson DL, Hellerstein S, Warady BA, Harris DJ. Metabolic and histologic investigation of the nature of nephrocalcinosis in children with hypophosphatemic rickets and the Hyp mouse. J Pediatr 1992 120 899-905. 

Several disorders of tubular phosphate handhng have been described. The best known of these is X-linked dominant hypophosphatemic rickets (previously known as vitamin D-resistant rickets). This disorder arises because of a defect in the PHEX gene. A defect of the sodium-dependent/ phosphate co-transporter has also been described, giving rise to autosomal recessive hereditary hypophosphatemic rickets with hypercalciuria. The molecular biology of tliese and other renal phosphate transport disorders has been reviewed. ... 

Osteomalacia and rickets may also occur because of phosphate depletion. The most common cause of rickets in the United States is hypophosphatemic osteomalacia (also known as hypophosphatemic vitamin D-resistant rickets and vitamin D-resistant rickets).This disorder is an X-linked dominant inherited trait characterized by renal phosphate wasting. Tubular phosphate wasting can also occur sporadically in adults and as part of Fanconi syndrome. Certain rare mesenchymal tumors may also produce a phosphaturic factor (phosphatonin or FGF-23), resultmg in renal phosphate wasting and osteomalacia. 

Harrell RM, Lyles KW, Harrelson JM, Friedman NE, Drezner MK. Heahng of bone disease in X-linked hypophosphatemic rickets/osteomalacia. J CUn Invest 1985 75 1858-68. 

Vitamin D (adult RDA = >100,000 units Familial X-linked hypophosphatemic rickets Unknown... 

Scriver, C. R., Goldbloom, R. B., and Roy, C. C., Hypophosphatemic rickets with renal hyperglycinuria, renal glucosuria, and glycyl-prolinuria. A syndrome with evidence for renal tubular secretion of phosphorus. Pediatrics 34, 357-371 (1964). 

The combination of hypophosphatemia, vitamin D resistance, osteomalacia, and rickets is seen in a number of syndromes (W24). These include (a) familial hypophosphatemic vitamin D-resistant rickets, a sex-linked, dominant disorder (P3), (b) familial vitamin D dependency, an autosomal recessive disorder due to la-hydroxylase deficiency (F19), and (c) nonfamilial hypophosphatemic osteomalacia (D9), considered by some workers (P3) to be a separate disease entity because of its late onset, its severity, and its lack of response to therapy. In addition, there are many inherited and acquired disorders which are associated with impairment of renal tubular reabsorption of phosphate, and these may be accompanied by hypophosphatemia, rickets, and relative vitamin D resistance. Serum alkaline phosphatase values in these disorders correlate poorly with the severity of the disease (A14) and with the response to therapy (E4, MclO, P7, S50). 

Stickler et al. (S69) claimed that serum alkaline phosphatase is increased in all patients with vitamin D-resistant rickets and used serum alkaline phosphate measurements to diagnose familial hypophosphatemic rickets in the neonatal period (S16, S68). However, it is generally thought that vitamin D-resistant rickets is not always accompanied by serum alkaline phosphatase elevation (Mc3). 

MclO. McNair, S. L., Stickler, G. B., Growth in familial hypophosphatemic vitamin D-resistant rickets. New Engl. J. Med. 281, 511-516 (1969). 

P3. Parfitt, A. M., Hypophosphatemic vitamin D refractory rickets and osteomalacia. Orthop. Clin. N. Amer. 3, 653-680 (1972). 

Stickler, G. B., Beabout, J. W., and Riggs, B, L., Vitamin D-resistant rickets Clinical experience with 41 typical familial hypophosphatemic patients and 2 atypical non familial cases. Mayo Clin. Proc. 45, 197-218 (1970). 

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