Hypophosphatemic vitamin -D- resistant rickets - Causes, Symptoms and Treatment .MF .

August 12, 2017 17:52 | Congenital Anomalies

Family hypophosphatemic rickets, diabetes, or phosphate, or vitamin-D-resistant rickets (HYPOPHOSPHATEMIC VITAMIN D-RESISTANT RICKETS; HPDR; 307800), first described Albrigt et al.in 1937.X-linked hypophosphatemic rickets - the most common form of hypophosphatemia, with incidence of about 1 in 20,000-25,000.

reasons hypophosphatemic rickets

disease is X-linked dominant inheritance.It is characterized by complete penetrance for hypophosphatemia and incomplete - for bone changes.Women pass a pathological feature of daughters and sons c probability of 50%, men - only daughters, with a probability of 100%.In boys, the disease is more severe than in girls.

Molecular-genetic cause of the disease - a mutation in the gene PHEX (Phosphat regulating hormone with homologies to endopeptidases on the X-chromosome).The gene consists of 18 exons and encodes a phosphate regulating endopeptidase (neutral endopeptidase homologous to regulate the activity of other proteins) controlling membrane phosphate transport in

kidney tubules, small bowel, and possibly in other organs.How mutations in the PHEX gene through a hypothetical fosfaturichesky hormone lead to renal loss of phosphate and vitamin D metabolism disorders, still remains unclear, and the views on this issue is very controversial.Hypothetical model: it is assumed that the endopeptidase PHEX causes activation fosfaturiticheskogo hormone.If a mutation in the gene PHEX-endopeptidase results in a loss of activity, thereby decreasing the activity fosfatonina and, ultimately, there is a loss of phosphate through the kidneys and no suppression of inactivation of 1,25- (OH) vitamin 3-D.


genetic defect leads to impaired reabsorption of phosphate in the renal tubule and its absorption in the small intestine.This is manifested giperfosfaturiya, hypophosphatemia, increased alkaline phosphatase activity and the development of rahitopodobnyh changes that can not be treated with vitamin D in normal doses.Hypocalcemia (calcium deficiency) or it is not insignificant.The concentration of nitrogenous waste products and electrolytes in the blood is normal.Other partial kidney function normal.The level of citrate in normal blood, in contrast to the ordinary gipotsitratemii vitamin deficient-D-rickets.

on bone radiographs revealed significant changes in the epi- and metaphyseal areas.diaphyseal structure differs from that of the ordinary rickets: there osteosclerosis area along with growth areas.There is thickening of the long bones due to one-sided, most of the medial layer of the periosteum.

Symptoms hypophosphatemic rickets

disease begins in the late first or early second year of life.Patients children have muscular hypotonia, varus deformities of the bones, especially of the lower extremities, rachitic "bracelets", "beads", gait disturbance - "duck" gait, stunted.Sometimes there are spontaneous fractures.The teeth erupt normally but quickly affected by caries.Mental development is not affected.

After the closure of the epiphyseal growth zones symptoms of the disease subside, but untreated patients into adulthood found severe bone disease.

Adults hereditary hypophosphatemia may be associated with osteomalacia.Clinically it is manifested bone pain, muscle weakness, decrease in growth due to the compression of the vertebrae.The calcium level in the blood is not broken, but there is a negative calcium-phosphorus balance.

Treatment hypophosphatemic rickets

Yet there is no satisfactory treatment of hypophosphatemic rickets.

Drug treatment has no effect on the basis of underlying genetic defect, however, when it achieved a clinical cure rickets and improve bone histology.Treatment should begin as soon as possible so that you can avoid bone deformities.The required dosage depends on the severity of rickets and the patient's age.Above them in small children (or at the beginning of therapy and in older children), then reduced to during growth spurt during puberty again increase.

In hereditary hypophosphatemic vitamin D-resistant rickets has pronounced tolerance to drugs ergocalciferol.Assigning them at doses corresponding to the physiological needs or used for the treatment of rickets caused by vitamin D deficiency, does not lead to an increase in phosphate in the blood, or to reduce the symptoms of rickets or osteomalacia.

Therefore it is necessary to use the medication in larger doses (average of 30 000-100 000 ME or more per day) for the treatment of fosfatdiabeta.No differences in efficacy ergocalciferol and cholecalciferol have been identified in this disease.Instead, these funds can be assigned digidrotahisterin at 0.5-1.5 mg per day.On chemical structure similar to last ergocalciferol.

Under the influence of large doses or ergocalciferol digidrotahisterina enhanced calcium absorption in the gut, improved balance of calcium and phosphorus, is reduced alkaline phosphatase activity, presumably due to the inhibitory effect of large doses of these drugs.In connection with this phenomenon of rickets and osteomalacia subside.Nevertheless excretion (selection) phosphate excretion is not reduced.Therefore, their blood is reduced, but the increase in patients with normal.

Forecast and complications

After puberty, the disease can take place even without treatment.In adults who have had a child vitamin-D-resistant rickets, hypophosphatemia persists, short stature, postrahiticheskie deformation pelvic limbs, often conditional cesarean section in women.Relapses are possible during the voltage of mineral metabolism (pregnancy, lactation).