Introduction
Vitamin D-resistant rickets are a type of tubular genetic defect that has both hypophosphatemia and hypocalcemia. Familial lowBlood phosphorus rickets(familial hypophosphatemic rickets) is due to renal tubular defects, the kidneys throw phosphorus, resulting in calcium, phosphorus metabolism disorders, causing rickets. The genetic method is sexually induced and inherited, and it has no response to the general physiological dose of vitamin D, so it is also called anti-vitamin D rickets and sexually linked hypophosphatemia.
the reason
Causes of familial hypophosphatemic rickets in children_What causes pediatric familial hypophosphatemic rickets
(1) Causes of the disease
The disease manifests as X-linked dominant inheritance, mainly due to the mutation of the PHEX gene located on the X chromosome, resulting in a decrease in renal tubular absorption of phosphorus.
(two) pathogenesis
Including the proximal renal tubular absorbing phosphorus and the defect of converting from 25-(OH)D to 1.25-(OH)2D3, causing blood phosphorus to decrease, ranging from 0.65 to 0.97 mmol/L (2 to 3 mg/dl). Excretion of urinary phosphorus is increased, and the calcium-phosphorus product is more than 30, and the bone is not easily calcified. In animal experiments, serum 1.25-(OH)2D3 levels have been confirmed to be lower than normal, and patients with familial hypophosphatemia continue to have hypophosphatemia and cannot stimulate the synthesis of 1,25-(OH)2D3. In addition, the use of oral phosphorus replacement therapy alone can not completely improve bone disease, and must be treated with 1.25-(OH)2D3 at the same time to correct bone softening.
Male patients can only pass the disease to girls. Female patients can be passed on to boys and girls. There are more female patients, but the symptoms are mild. Most of them have only low blood phosphorus and no obvious skeletal changes. The incidence of men is low, but the symptoms are more serious. It is now known that the transcriptional protein is on chromosome 5, and the gene of this disease is in Xp22.31 to p21.3. Occasionally some cases belong to autosomal recessive inheritance. Some cases are sporadic and have no family history.
symptom
Symptoms of familial hypophosphatemic rickets in children_What are the symptoms of familial hypophosphatemic rickets in children?
At the age of nearly one year, the lower limbs began to bear the weight, only to find the symptoms, the beginning of the disease often with "O" shaped legs or "X" legs as the earliest symptoms, other signs of rickets are very light, less ribbed beads and Hao's ditch, lack of nutritional vitamins D lack of common rickets, low muscle tone. Often not noticed by parents. Heavier cases have progressive bone deformities and multiple fractures, and bone pain, especially in the lower limbs, can not even walk. Severe deformity, the growth of body length is often affected. Poor dentin, toothache, easy to fall off the teeth and not easy to regenerate. No response to general doses of vitamin D, low blood phosphorus, increased urinary phosphorus.
diagnosis
According to the clinical manifestations, except for the rickets caused by other causes, there is no response to the general dose of vitamin D. Combined with laboratory tests for hypophosphatemia and increased urinary phosphorus, the diagnosis can be confirmed.
Identification
1. Identification of vitamin D deficiency rickets The identification of this disease and vitamin D deficiency rickets lies in the following characteristics:
(1) The intake of vitamin D has exceeded the general requirement and there is still a skeletal change in active rickets.
(2) There is still activity of active rickets after 2 to 3 years old.
(3) Intramuscular injection of 400,000 to 600,000 U of vitamin D, the blood phosphorus increased in a few days for children with general D deficiency rickets, and the long bone X-ray showed improvement in 2 weeks, but the patients did not have these changes.
(4) Hypophosphatemia is common among family members and is a feature of low phosphorus anti-D rickets.
2. Identification of low blood calcium anti-vitamin D rickets This disease is also associated with low blood calcium anti-vitamin D rickets.
The latter, also known as vitamin D dependent rickets, is less common because the kidney lacks 1-hydroxylase and cannot synthesize 1.25-(OH)2D3. The onset time is often accompanied by muscle weakness from several months after birth, and early hand and foot sputum can occur. Blood calcium is reduced, blood phosphorus is normal or slightly lower, blood chlorine is increased, and amino acid urine can occur. Although it is treated with conventional dose of vitamin D, it still shows signs of rickets on X-ray long bone tablets. To increase the amount of vitamin D to 10,000 U / d or dihydrotachysterol (DHT) 0.2 ~ 0.5 mg / d to see the effect. It was cured by treatment with 0.25 to 2 μg of 1.25-(OH)2D3. This disease is generally autosomal recessive.
3. In addition, the disease must be differentiated from Fanconi syndrome and renal tubular acidosis.
complication
There are progressive bone deformities and multiple fractures, bone pain, and even walking. Poor dentin. short and small.
treatment
Western medicine treatment
The principle of treatment is to prevent bone deformity and increase blood phosphorus as much as possible, and maintain it above 0.97mmol/L (3mg/dl), which is beneficial to bone calcification. Maintain normal growth rate, and avoid high urinary calcium and hypercalcemia caused by vitamin D poisoning. Briefly describe the advantages and disadvantages of various measures as follows:
1. Oral phosphate alone to improve blood phosphorus to normal levels, often requires phosphate preparations. Generally, a phosphate mixture of 58.8 g/L of phosphoric acid and 136 g/L of disodium hydrogen phosphate is used, and 30.4 mg of elemental phosphorus is contained per 1 ml, 5 times a day. For example, each time 5ml, 760mg of elemental phosphorus is added every day. Infants and young children are 0.5 ~ 1g / 24h, children are 1 ~ 4g / 24h. Phosphate preparations are unpleasant and prone to nausea and diarrhea. In order to better promote the absorption of phosphorus in the intestine, it is best to give vitamin D or DHT at the same time.
2. Phosphate and vitamin D use vitamin D2 in an amount of 50,000 to 200,000 U/24h. Vitamin D is easy to accumulate in body fat, until a large amount of accumulation can be found to be poisoned, so it is easy to cause poisoning.
3. DHT is a product similar to vitamin D. It has a vitamin D effect after being hydroxylated in the body. It is not easy to accumulate in body fat, and it is not easy to be poisoned. It is safe and the dosage is 0.02mg/(kg·d).
4.1.25-(OH)2D3 The dose is 50-65 mg/(kg·d). After treatment, plasma alkaline phosphatase decreased to normal, but blood phosphorus continued to be low, so it should be taken with phosphate preparations, and the curative effect is better.
5. Prevention of hypercalcemia In order to prevent hypercalcemia, check 24h urinary calcium and urinary creatinine every 1 to 3 months. The ratio of urinary calcium to urinary creatinine is normally 0.15 to 0.3. If this ratio is greater than 0.4, the dose of vitamin D or DHT is too large and should be reduced early to reduce the chance of poisoning. It has been advocated to use diuretics such as hydrochlorothiazide (hydrochlorothiazide) 1.5 ~ 2mg / (kg · d), oral administration, to avoid hypercalcemia, and can significantly increase blood phosphorus concentration.
prevention
The disease manifests as X-linked dominant inheritance. Male patients pass the disease to girls, female patients can be passed to boys and girls; occasionally some cases are autosomal recessive; some cases are sporadic. The prevention method refers to the prevention method of congenital diseases. The causes of congenital diseases are very complex, including infections during pregnancy, advanced births, close relatives, radiation, chemicals, autoimmunity, and genetic abnormalities. Preventive measures and other birth defects, in order to reduce and reverse the incidence of neonatal birth defects, prevention should be from pre-pregnancy to prenatal.
Pre-marital medical examination plays an active role in preventing birth defects. The size of the effect depends on the examination items and contents, including serological examination (such as hepatitis B virus, treponema pallidum, HIV), reproductive system examination (such as screening for cervical inflammation), Ordinary medical examinations (such as blood pressure, electrocardiogram) and asking about the family history of the disease, personal medical history, etc., do a good job in genetic disease counseling.
Pregnant women should avoid harmful factors as much as possible, including away from smoke, alcohol, drugs, radiation, pesticides, noise, volatile harmful gases, and toxic and harmful heavy metals. Systemic birth defect screening is required during antenatal care during pregnancy, including regular ultrasound, serological screening, and, if necessary, chromosomal examination.
Once an abnormal result occurs, it is necessary to determine whether to terminate the pregnancy; the safety of the fetus in the uterus; whether there is sequelae after birth, whether it can be treated, and how the prognosis is. Take practical and feasible treatment measures.
The prenatal diagnostic techniques used are: 1 amniocentesis cell culture and related biochemical tests (amniotic puncture time is appropriate for 16 to 20 weeks of pregnancy); 2 maternal blood and amniotic fluid alpha-fetoprotein determination; 3 ultrasound imaging (applicable in about 4 months of pregnancy) 4X line examination (after 5 months of pregnancy) is beneficial for the diagnosis of fetal skeletal malformation; 5 chromatin determination of villus cells (40 to 70 days of conception), predicting fetal sex to help diagnose X-linked genetic diseases; 6 application gene linkage analysis; 7 fetal microscopy.
Through the application of the above technology, the birth of a fetus with severe genetic diseases and congenital malformations is prevented.
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