Tubulopathy manifested rahitopodobnyh syndrome

August 12, 2017 17:51 | Genetic Diseases

Vitamin D-resistant rickets (phosphate diabetes) .Leading signs are rahitopodobnyh skeletal changes, mainly lower limbs.The most common signs of a vitamin D-resistant rickets occur in the second year of life and are progressive in nature.However

demonstration (first manifestation) vitamin D-pezistentnogo rickets could be the first year of life (early demonstration) and 6-8 years of age (late onset).Changes in bone accompanied by delayed physical development and a violation of the child's gait ( "duck walk").The changes of the skeleton are progressive in nature and help delay the development of static-motor functions of a sick child.Intellect children usually suffers.The characteristic biochemical signs of phosphate diabetes are: low level of serum phosphorus, increased release of phosphates in the urine;blood calcium level is usually normal.Alkaline phosphatase activity increased blood.

resistance (resistance) of the body to vitamin D first reported in 1937. Initially, it was associated with a violat

ion of intestinal calcium absorption, secondary hyperparathyroidism (increased parathyroid function) and a decrease in the reabsorption (reuptake) of phosphate by the kidney.Subsequently, however, this mechanism has not been confirmed, usually the calcium content in the blood of patients does not change the activity of PTH (parathyroid hormone) increases substantially.Reduced quantities

phosphate plasma concentration leads to increasing their reabsorption in the proximal tubule.The major regulatory role is played by PTH (parathyroid hormone), increasing its concentration in the blood inhibits the reabsorption of phosphate, leading to the appearance of excessive amounts of it into urine.In the distal tubule reabsorption of phosphate and parathyroid hormone is suppressed.

Vitamin D increases the reabsorption of phosphate in the renal tubules, t. E. The action of this substance is the opposite effect of PTH and is localized in the proximal tubules.

There are currently 4 hypothesis, according to which the basis of phosphate diabetes may underlie these metabolic and functional disorders:

1) a primary defect in violation of the processes of absorption of calcium and phosphorus in the intestine;

2) tubulopathy with a primary violation of phosphate reabsorption in the renal tubules;

3) genetically determined defect sochetannyj renal tubules and bowel;

4) violation of the synthesis of vitamin D and inadequate education of its active form in the liver.

a result of genetic defects of phosphate transport in phosphate diabetes develops significant shortage of phosphorus and calcium in the body, which leads to the formation of the skeleton rahitopodobnyh changes.This is facilitated in some cases, excessive secretion of PTH (parathyroid hormone).Phosphate-diabetes is characterized by a pronounced diversity of clinical manifestations.Depending on the timing of demonstrations (first manifestation), clinical and biochemical characteristics, the nature of the response to the introduction of vitamin D are 4 variants of the disease.

1st variant characterized by early onset of the disease (1 st year of life), a minor degree of bone deformities, decrease of calcium in the blood, increased allocation of phosphorus in the urine, increased levels of parathyroid hormone in the blood, good tolerability of vitamin D.The development of this embodiment, the disease associated with the simultaneous involvement in pathological process intestine and renal tubules and significant loss of phosphorus and calcium through intestine, and kidneys.

2nd version characterized by late onset - in the 2nd year of life, severe bony changes, reducing the amount of phosphorus in the blood serum, urinary excretion of large amounts of phosphates, resistance (resistance) to high doses of vitamin D. The development of thisdiseases caused advantageous embodiment renal tubular defect (decrease phosphate reabsorption intensity) phosphates and loss mainly in urine.

third embodiment differs late onset disease - 5-6 years of age, the severity of skeletal abnormalities, a pronounced decrease in the amount of calcium in blood serum, a significant decrease in the absorption of phosphate in the gut the normal or slight excretion of these compounds from urine.There is substantial resistance (resistance) to vitamin D. The development of this variant of the disease is associated with primary involvement in the pathological process of the intestine and malabsorption and assimilation of calcium and phosphorus in the intestine.

4th option - characterized by increased sensitivity to vitamin D and the propensity to develop clinical and biochemical picture of hypervitaminosis D (vomiting, nausea, thirst, increased calcium in the blood, as well as strengthening its excretion in the urine) in responseto small doses of vitamin D. Clinically it is characterized by the manifestation on the 2nd year of life and moderate bone deformities.

contingent for a special screening for phosphate diabetes are children:

1) with clinical vitamin D-deficient rickets and lack of effect of conventional therapy antirahiticheskoy vitamin D;

2) with one of the parents, the patient rahitopodobnyh disease;

3) with bone deformities of the lower limbs;

4) from families with impaired calcium-phosphorus metabolism.

The main criteria for the diagnosis of phosphate diabetes are:

1) clinical manifestations:

a) progressive nature of bone deformities of the lower limbs;

b) the lag in physical development;

2) the type of inheritance:

a) the dominant;

b) linked to the X chromosome;

3) biochemical abnormalities:

a) low level of serum phosphorus;

b) an increase in phosphorus excretion in the urine;

c) the normal total blood calcium indicators;

d) increasing the activity of alkaline phosphatase blood;

d) raising of parathyroid hormone in the blood;

e) reducing the absorption of calcium and phosphorus in the intestine.

Features phosphate treatment of diabetes. applied conservative and surgical methods of treatment.Drug treatment should be carried out taking into account the individual tolerance of drugs, a process activity in bone, and clinical and biochemical variants of the disease.

indications for conservative treatment are: an active process in the bone (by X-ray data), elevated alkaline phosphatase blood, increased phosphate excretion in the urine, the preparation of children for surgical correction.

Contraindications to conservative therapy with vitamin D are idiosyncrasy of vitamin D, excessive excretion of calcium in the urine, the lack of an active process in the bone tissue according to the laboratory and radiological studies.

main drugs in the therapy include vitamin D and its metabolites.The initial dose of vitamin D is 10 000-15 000 IU per day.Increasing the initial doses of vitamin D should be under the control of calcium and phosphorus indicators of blood serum and urine, blood alkaline phosphatase activity, the level of research that should be done every 10-14 days.Increased blood levels of phosphorus, decreased blood alkaline phosphatase activity, as well as recovery for X-ray data give reason not to increase the dose of vitamin bone structure D. The maximum daily dose of vitamin D, depending on the options phosphate diabetes are: at the 1st version - 85-100 thousand units per day, with a 2-m. - 150-200 thousand units a day, at 3-m. - 200-300 thousand units per day..At the 4th version of the appointment of vitamin D is contraindicated.Because vitamin D metabolites used domestic product - oksidevit a daily dose of 0.25-3 mg.In its application requires particularly strict control of blood calcium level (determined by 1 every 7-10 days);on an outpatient basis for these purposes, you can use the sample Sulkovicha.

In the complex treatment of phosphate diabetes necessarily used calcium supplements (calcium gluconate or calcium chloride) and phosphorus (inorganic phosphates, phytin or calcium glycerophosphate).Process for improving absorption of calcium and phosphate in the gut is recommended for a long period (5-6 months) application of inwardly citrate mixtures (citric acid, sodium citrate and purified water) at 20-50 ml per day.The active phase of the disease when there may be pain in the bones and joints, we recommend a two-week stay in bed.During the clinical and laboratory remission and surveillance in outpatient conditions recommended limitation of physical activity (prohibition of jumps, physical exercise using a special gentle program) holding therapeutic massage, salt-coniferous baths, spa treatment.

indicator of the effectiveness of conservative treatment are: improvement of general condition, increase the rate of growth of children, normalization or substantial improvement in calcium-phosphorus metabolism, lowering blood alkaline phosphatase activity and the positive development of the structural changes of bone tissue (according to X-ray examination).

Complex treatment with (carried out every 10-14 days to determine their levels) of massive doses of vitamin D should be under constant medical supervision for the individual reactions of the child (daily control) and indicators of calcium and phosphorus blood and urine.The appearance of clinical symptoms of hypervitaminosis D (thirst, vomiting, abdominal pain, refusal to eat) or biochemical signs (increased blood calcium levels, increasing its excretion in the urine) is an indication for the abolition of vitamin D and its metabolites.

prerequisite for surgical treatment is to achieve a persistent clinical and biochemical remission for at least 2 years.

vitamin D-dependent rickets (psevdovitamin D-deficient rickets). first signs of vitamin D-dependent rickets characterized by functional changes in the central nervous system that manifests excessive sweating, sleep disturbance, WinCE.Later joined by bone changes (deformation of the lower limbs, chest, skull, rachitic "rosary", "brasletki").Sometimes the background of these changes in children have short-term seizures, often provoked by fever.The most common vitamin D-dependent rickets developing in the first 3-5 months of life and is progressive in nature, although previously carried out or prevention of rickets is usually conducted antirahiticheskoe treatment.Less commonly, the disease can begin at 3-5 years of age.

Disease characterized by the following biochemical disorders: low levels of serum calcium, normal or slightly reduced level of blood phosphate, increased alkaline phosphatase activity of blood, a significant decrease in calcium excretion in the urine, an increase in the amount of output per day of amino acids in the urine.A deficiency of vitamin D and its active metabolites is accompanied by increased production of parathyroid hormone, which leads to the appearance of urinary phosphate and amino acids (and aminoaciduria phosphaturia respectively).

vitamin D-dependent rickets is caused by an autosomal recessive mode of inheritance, but often there are sporadic cases of the disease, characterized by apparently fresh primary mutations.Depending on the depth of metabolic disorders distinguish two clinical and biochemical variant D-dependent rickets with severe and moderate severity of metabolic disorders and bone deformities.

primary version is characterized by severe bone changes (observed deformation of the lower limbs, chest deformation, forearms), a pronounced decrease in blood calcium levels (hypocalcemia), high levels of alkaline phosphatase activity of blood, deep disturbances of bone structure by X-ray data.Second embodiment

inherent light or moderate bone deformities, particularly the lower limbs, a moderate decrease in calcium content in serum, structurally unstable changes in bone structure by X-ray data.

development of the first variant is associated with severe deficiency of vitamin D, and the second option - with a reduction in the sensitivity of organs to this link.

symptoms for special examinations:

1) expressed and progressive rachitic skeletal changes;

2) the lack of therapeutic effect of preventive treatment doses of vitamin D;

3) convulsive disorder of unknown origin, in conjunction with the rachitic changes in young children.Features of metabolic disorders in this disease include:

1) a decrease of calcium in the blood serum (hypocalcaemia);

2) increase the activity of alkaline phosphatase blood;

3) increased release of phosphate and amino acids in the urine;

4) normal levels of vitamin D blood.

antirahiticheskogo Efficacy of treatment: no effect, despite conducted antirahiticheskoe treatment with vitamin D.

greatest difficulties arise with the delimitation of the vitamin D-dependent rickets and normal in young children.The main arguments for vitamin D-dependent rickets are progressive nature of bone deformations, despite conventional treatment antirahiticheskoe, low serum calcium and vitamin D. normal control in the administration of vitamin D is used as a diagnostic test in a dose of 4000 IU per day for6-8 weeks.When vitamin D-deficient rickets normalization clinical and biochemical parameters, and this dose is ineffective in the D-dependent.Due to the fact that the development of the disease leading to a deficiency of vitamin D, most suitable oksidevitom replacement therapy, which is a biologically active analogue of vitamin D. oksidevita Daily doses administered depending on individual tolerance and disease severity.In the absence of oksidevita can be used vitamin D. The initial doses are 10 to 15 thousand units, the maximum -. 40-60 thousand units per day..

The range of therapeutic agents are strongly advised to include calcium supplements (calcium gluconate) and phosphorus (phytin), vitamins A, C, E, a mixture of citrate courses for 3 to 5 months.

When using drugs of vitamin D, particularly its active metabolites, a systematic (1 every 10-14 days) for the control of blood levels of calcium and phosphorus and their urinary excretion.Increased blood calcium or urinary excretion suggests the development of hypervitaminosis D and requires discontinuation of the drug.Reappointment of vitamin D or oksidevita possible only after 7-10 days in half (from the original) dose with careful clinical and laboratory monitoring.

Children with vitamin D-dependent rickets positive dynamics of calcium-phosphorus metabolism during treatment usually occurs within 4-6 weeks after the beginning of combined therapy.It should be borne in mind that after the cancellation of vitamin D in children (usually 3-6 months) may occur exacerbation reappearance of clinical symptoms of the disease, therefore the treatment of patients must be conducted continuously for several years.When appointed early and adequate therapy, especially when using oksidevita, clinical and biochemical signs of illness in infants regress.In cases of late diagnosis, when he developed severe and rough bone deformation of the lower limbs, impeding movement, operative treatment.