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 D₃ 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 small-cell mesenchymal tumors that produce a humoral factor that decreases proximal renal tubular resorption of phosphate (oncogenic rickets).

Pathophysiology

The observed abnormality is decreased proximal renal tubular resorption of phosphate, resulting in hypophosphatemia. This defect is due to a circulating factor or factors and is associated with a primary abnormality in osteoblast function. 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 in Ca-deficient rickets (see Vitamin Deficiency, Dependency, and Toxicity: Vitamin D Deficiency and Dependency). Because 1,25-dihydroxyvitamin D₃ levels are normal to slightly low, a defect in conversion is presumed; hypophosphatemia would normally cause elevated 1,25-dihydroxyvitamin D₃ levels.

Symptoms and Signs

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, 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.

Diagnosis

• Serum levels of Ca, phosphate, alkaline phosphatase, 1,25-dihydroxyvitamin D₃, and PTH
• Urinary phosphate levels

Serum phosphate levels are depressed, but urinary phosphate excretion is large. Serum Ca and PTH are normal, and alkaline phosphatase often is elevated. In Ca-deficient rickets, hypocalcemia is present, hypophosphatemia is mild or absent, and urinary phosphate is not elevated.

Treatment

• Oral phosphate and calcitriolSome Trade Names
  ROCALTROL
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Treatment consists of neutral phosphate solution or tablets. Starting dose in children is 10 mg/kg (based on elemental phosphorus) po qid. Because this phosphate may cause hyperparathyroidism, vitamin D is given as calcitriolSome Trade Names
ROCALTROL
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, 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 calcitriolSome Trade Names
ROCALTROL
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5 to 10 ng/kg po bid and elemental phosphorus 250 mg to 1 g po tid or qid.

Last full review/revision September 2009 by Peter C. Brazy, MD

Content last modified February 2012