(Vitamin D-resistant rickets)
The hypophosphatemic rickets is an inherited disorder that is characterized by a hypophosphatemia, a disturbed intestinal calcium absorption and a rickets or osteomalacia that does not improve after vitamin D supplementation. It is usually hereditary. The symptoms are bone pain, fractures and growth disorders. The diagnosis is usually carried out by determination of the serum level of phosphate, alkaline phosphatase, and 1,25-dihydroxyvitamin D3. is treated with oral phosphate and calcitriol.
The hereditary hypophosphatemic rickets is inherited X-linked dominant in general. Other inheritance pattern may occur, but are rare.
The hypophosphatemic rickets is an inherited disorder that is characterized by a hypophosphatemia, a disturbed intestinal calcium absorption and a rickets or osteomalacia that does not improve after vitamin D supplementation. It is usually hereditary. The symptoms are bone pain, fractures and growth disorders. The diagnosis is usually carried out by determination of the serum level of phosphate, alkaline phosphatase, and 1,25-dihydroxyvitamin D3. is treated with oral phosphate and calcitriol. The hereditary hypophosphatemic rickets is inherited X-linked dominant in general. Other inheritance pattern may occur, but are rare. Sporadic cases are acquired sometimes associated with benign mesenchymal tumors that produce a humoral factor that reduces the proximal renal tubular reabsorption of phosphates (tumor-induced osteomalacia). Pathophysiology pathology is reduced phosphate absorption in the proximal renal tubule, which leads to renal Phosphatauszehrung and hypophosphatemia. This defect results from circulating factors that phosphatonins be mentioned. The principle-phosphatonin in hereditary hypophosphatemic rickets is FGF-23rd The intestinal calcium and phosphate absorption may also be decreased. The reduced bone density caused by the rather low levels of phosphate and osteoblasts disorder as by low calcium and the increased parathyroid hormone (PTH) as in “calcipenic” rickets (vitamin D deficiency and dependence). Hypophosphatemia would normally lead to increased 1,25-dihydroxyvitamin D3 levels. Since the 1,25-dihydroxyvitamin D3 levels are normal or slightly decreased, one suspects an error in the conversion. It is known that a form of hereditary rickets with hypercalciuria (HHRH) Type 2c occur sodium phosphate co-transporter due to mutations in the proximal tubule. A defective phosphate transport and hypophosphatemia lead in this case to appropriately elevated 1,25-dihydroxyvitamin D3 levels, thus leading to hypercalciuria. Symptoms and signs The disease manifests itself with a whole spectrum of abnormalities ranging from the sole hypophosphatemia up to advanced rickets or osteomalacia. Children imagine usually after they start to run, with a bending of the legs and other bone deformities, pseudo fractures (ie X-ray findings in osteomalacia, the areas may represent earlier stress fractures that have been replaced vs. by unangemesses mineralized osteoid areas of bone erosions ), bone pain and short stature. Hyperostoses to the muscle attachments may hinder movements. Rickets of the spine or pelvis, dental enamel defects, and tetany, as occur in vitamin D deficiency are rarely present in hypophosphatemic rickets. Patients with nephrolithiasis HHRH may have and / or nephrocalcinosis. Diagnostic serum levels of calcium, phosphate, alkaline phosphatase, 1,25-dihydroxyvitamin D3, PTH, FGF-23, and creatinine phosphate and creatinine in the urine (for calculating the tubular reabsorption of phosphate) X-ray photographs of the bone Serum phosphorus levels are low, the excretion but in the urine is very high. Serum calcium and PTH are normal, the alkaline phosphatase is often increased. The hypophosphatemia-induced stimulation of calcitriol production does not take place. Typically, the calcidiol levels are normal, while the calcitriol levels to low normal. A “calcipenic” Rickets is a hypocalcemia, hypophosphatemia a mild or absent, and the levels of phosphate in the urine is not increased. Oral treatment phosphate and Calcitriol Treatment of a hypophosphatemic rickets is in a neutral phosphate solution or tablets. The initial dose for children is 10 mg / kg (based on elemental phosphorus) p.o. 4 times a day. Phosphatsupplementierung reduces ionized calcium concentrations and also inhibits calcitriol conversion, leading to secondary hyperparathyroidism and aggravates the Phosphatauszehrung in urine. Therefore, vitamin D and calcitriol initial 5-10 ng / kg p.o. 2 times given daily. However, this is not the case with HHRH, wherein 1,25-dihydroxyvitamin D3 level increases, and the dosage may be disadvantageous with calcitriol. The phosphate dosage must be increased to improve bone growth or to relieve bone pain. However, diarrhea can restrict the oral dosage phosphate. The plasma concentration of phosphate increases the alkaline phosphatase falls, the heals rickets and growth improves. Hypercalcemia, hypercalciuria and nephrocalcinosis with reduced renal function may lead to complications in the treatment. Treated patients need frequent follow-up visits. Adults with oncogenic rickets can quickly healthy when the mesenchymal tumor that caused the fault is removed. Otherwise, the oncogenic rickets with calcitriol 5-10 ng / kg p.o. p.o. 2 times daily and elemental phosphorus with 250 mg-1 g treated 3-4 times daily. Important points Decreased renal reabsorption of phosphate leads to renal Phosphatauszehrung and hypophosphatemia. There is a lack of bone mineralization due to low levels of phosphate and osteoblast dysfunction. The children have stunted growth, bone pain and deformation (z. B. leg bending) and short stature. Patients with rickets with hypercalciuria (HHRH) may have nephrolithiasis and / or nephrocalcinosis. The diagnosis is made by low serum phosphate levels, increased phosphate in urine and normal calcium and PTH are found in the serum. Treatment is with oral phosphate supplements and, except for HHRH, vitamin D (calcitriol as a given).