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(Vitamin D–Resistant Rickets)
Hypophosphatemic rickets is a disorder characterized by hypophosphatemia, defective intestinal absorption of Ca, and rickets or osteomalacia unresponsive to vitamin D. It is usually hereditary. Symptoms are bone pain, fractures, and growth abnormalities. Diagnosis is by serum phosphate, alkaline phosphatase, and 1,25-dihydroxyvitamin D 3 levels. Treatment is oral phosphate plus calcitriol.
Familial hypophosphatemic rickets is usually inherited as an X-linked dominant trait; other familial patterns occur but are rarer.
Sporadic acquired cases sometimes are associated with benign mesenchymal tumors that produce a humoral factor that decreases proximal renal tubular resorption of phosphate (tumor-induced osteomalacia).
The observed abnormality is decreased proximal renal tubular resorption of phosphate, resulting in renal phosphate wasting and hypophosphatemia. This defect is due to circulating factors called phosphatonins. The principle phosphatonin in hereditary hypophosphatemic rickets is FGF-23. Decreased intestinal Ca and phosphate absorption also occurs. Deficient bone mineralization is due to low phosphate levels and osteoblast dysfunction rather than to the low Ca and elevated parathyroid hormone (PTH) levels as in calcipenic rickets (see Vitamin D Deficiency and Dependency). Because 1,25-dihydroxyvitamin D 3 levels are normal to slightly low, a defect in conversion is presumed; hypophosphatemia would normally cause elevated 1,25-dihydroxyvitamin D 3 levels.
The disease manifests as a spectrum of abnormalities, from hypophosphatemia alone to growth retardation and short stature to severe rickets or osteomalacia. Children usually present after they begin walking, with bowing of the legs and other bone deformities, pseudofractures (ie, x-ray findings in osteomalacia that may represent areas of prior stress fractures that have been replaced by inadequately mineralized osteoid vs areas of bony erosions), bone pain, and short stature. Bony outgrowth at muscle attachments may limit motion. Rickets of the spine or pelvis, dental enamel defects, and tetany that occur in dietary vitamin D deficiency are rarely present in hypophosphatemic rickets.
Serum phosphate levels are depressed, but urinary phosphate excretion is large. Serum Ca and PTH are normal, and alkaline phosphatase often is elevated. Hypophosphatemia-induced stimulation of calcitriol production does not occur. Typically, calcidiol levels are normal, whereas calcitriol levels are normal to low. In calcipenic rickets, hypocalcemia is present, hypophosphatemia is mild or absent, and urinary phosphate is not elevated.
Treatment consists of neutral phosphate solution or tablets. Starting dose in children is 10 mg/kg (based on elemental phosphorus) po qid. Phosphate supplementation lowers ionized Ca concentrations and further inhibits calcitriol conversion, leading to secondary hyperparathyroidism and exacerbating urinary phosphate wasting. Therefore, vitamin D is given as calcitriol, initially 5 to 10 ng/kg po bid. Phosphate dose may need to be increased to achieve bone growth or relieve bone pain. Diarrhea may limit oral phosphate dosage. Increase in plasma phosphate and decrease in alkaline phosphatase concentrations, healing of rickets, and improvement of growth rate occur. Hypercalcemia, hypercalciuria, and nephrocalcinosis with reduced renal function may complicate treatment. Patients undergoing treatment need frequent follow-up evaluations.
Adults with oncogenic rickets may dramatically improve once the mesenchymal tumor that causes the disorder is removed. Otherwise, oncogenic rickets is treated with calcitriol 5 to 10 ng/kg po bid and elemental phosphorus 250 mg to 1 g po tid or qid.
Decreased renal resorption of phosphate results in renal phosphate wasting and hypophosphatemia.
There is deficient bone mineralization due to low phosphate levels and osteoblast dysfunction.
Children have growth retardation, bone pain and deformities (eg, leg bowing), and short stature.
Diagnose by finding low serum phosphate levels, elevated urinary phosphate, and normal serum Ca and PTH.
Treat with oral phosphate supplements and vitamin D (given as calcitriol).
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