Hypophosphatemic Rickets

Hypophosphatemic rickets is a disorder characterized by hypophosphatemia, defective intestinal absorption of calcium, and rickets or osteomalacia unresponsive to vitamin D. It is usually hereditary. Symptoms are bone pain, fractures, and growth abnormalities.

Causes of Hypophosphatemic Rickets #

• 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 fibroblast growth factor-23 (FGF-23).

• Decreased intestinal calcium and phosphate absorption also occurs.

• Deficient bone mineralization is due to low phosphate levels and osteoblast dysfunction rather than to the low calcium and elevated parathyroid hormone (PTH) levels as in calcipenic rickets.

• 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 of Hypophosphatemic Rickets #

• 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pseudofractures (ie, x-ray findings in osteomalacia that may represent areas of prior stress fractures that have been replaced by inadequately mineralized osteoid vs areas of bony erosions), bone pain, and short stature.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.

Diagnosis of Hypophosphatemic Rickets #

Diagnosis include the following

• Serum levels of calcium, phosphate, alkaline phosphatase, 1,25-dihydroxyvitamin D3, PTH, FGF-23, and creatinine

• Urinary phosphate and creatinine levels (for calculation of the tubular reabsorption of phosphate)

• Bone x-rays

Results show the following

• Serum phosphate levels are depressed, but urinary phosphate excretion is large.

• Serum calcium 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 of Hypophosphatemic Rickets #

• Treatment of hypophosphatemic rickets consists of neutral phosphate solution or tablets.

• Starting dose in children is 10 mg/kg (based on elemental phosphorus) 4 times a day.

• Phosphate supplementation lowers ionized calcium concentrations and further inhibits calcitriol conversion, leading to secondary hyperparathyroidism and exacerbating urinary phosphate wasting.

• Therefore, oral vitamin D is given as calcitriol, initially 5 to 10 ng/kg 2 times a day.

• This, however, is not the case with HHRH or HHN (hypophosphatemia, hypercalcemia, and nephrocalcinosis), where 1,25-dihydroxyvitamin D3 levels are elevated and dosing with calcitriol can be detrimental.

• 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.