Pediatric familial hypophosphatemic rickets
Introduction
Introduction to familial hypophosphatemic rickets in children Vitamin D-resistant rickets (vitamin D-resistantrickets) is a renal tubular genetic defect disease with hypophosphatemia and hypocalcemia. Familial hypophosphatemic rickets are due to tubular defects and kidneys. Phosphorus is lost, resulting in disorder of calcium and phosphorus metabolism, 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. basic knowledge The proportion of sickness: 0.0052% Susceptible people: children Mode of infection: non-infectious Complications: fracture
Cause
Causes of familial hypophosphatemic rickets in children
(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 from 25-(OH)D to 1,25-(OH)2D3, resulting in a decrease in blood phosphorus, ranging from 0.65 to 0.97 mmol/L (2 to 3 mg/dl). ), urinary phosphorus exclusion increased, calcium and phosphorus products are more than 30, bone is not easy to calcify, serum 1,25-(OH)2D3 levels have been confirmed in animal experiments, due to patients with familial hypophosphatemia, Continuous hypophosphatemia, can not stimulate the synthesis of 1,25-(OH)2D3, in addition, the use of oral phosphorus replacement therapy alone can not completely improve bone disease, must be treated with 1,25-(OH)2D3 at the same time to correct osteomalacia .
Male patients can only pass the disease to girls, female patients can be passed to boys and girls, female patients are more, but the symptoms are light, most of them only have low blood phosphorus and no obvious skeletal changes, males have low incidence, but the symptoms are more serious. It is now known that the transcriptional protein is on chromosome 5. The gene of this disease is in Xp22.31~p21.3. Occasionally, some cases are autosomal recessive, and some cases are sporadic and have no family history.
Prevention
Prevention of familial hypophosphatemic rickets in children
The disease manifests as X-linked dominant inheritance. Male patients pass the disease to girls. Female patients can be passed on to boys and girls. Occasionally, some cases are autosomal recessive, and some cases are sporadic. Prevention methods According to the prevention methods of congenital diseases, the causes of congenital diseases are very complicated, including infection during pregnancy, advanced birth, close relatives, radiation, chemical substances, autoimmune, genetic material abnormalities, etc., preventive measures and other birth defects Disease, 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) and reproductive system examination (such as screening for cervical inflammation). General 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 far as possible, including away from smoke, alcohol, drugs, radiation, pesticides, noise, volatile harmful gases, toxic and harmful heavy metals, etc. In the process of antenatal care during pregnancy, systematic screening of birth defects is required, including Regular ultrasound examination, serological screening, etc., if necessary, a chromosome 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, how to prognose, etc., and take practical measures for diagnosis and treatment.
Complication
Complications of familial hypophosphatemic rickets in children Complications
There are progressive bone deformities and multiple fractures, bone pain, or even walking, poor dentin and short stature.
Symptom
Symptoms of familial hypophosphatemic rickets in children Common symptoms Low blood phosphorus vitamin D deficiency urinary phosphorus toothache X-legs Knee varus valgus or hip varus metabolism Reduced bone pain Neonatal hypophosphatemia infants baldness
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 lower limbs, can not even walk, severe deformity, growth of body length Affected, poor dentin, toothache, easy to fall off the teeth and not easy to regenerate, no response to the general dose of vitamin D, low blood phosphorus, increased urine phosphorus.
Examine
Examination of familial hypophosphatemic rickets in children
The main biochemical abnormalities seen in the laboratory are hypophosphatemia, but attention should be paid to the relationship between gender, age and serum. The serum phosphorus value decreases by 0.48-0.97mmol/L (1.5-3.0mg/dl), mostly at 0.65mmol. /L (2mg/dl), blood calcium value is normal or slightly decreased, serum alkaline phosphatase activity is increased, although there is hypophosphatemia, but urinary phosphorus is still increased, indicating renal tubular reabsorption of phosphorus, from No amino acid urine, glucose urine, phosphate and potassium were found. It was found that even renal tubular phosphorus reabsorption was found.
In the first few months of life, because the glomerular filtration rate is quite low, serum phosphorus concentration may be normal, so the earliest laboratory abnormalities may be increased serum alkaline phosphatase activity, normal urine and renal function, renal tubular regurgitation The absorption rate of phosphorus decreased, and the X-ray bone slices showed rickets changes of different severity. The active and recovery lesions existed at the same time. The femur and tibia were most easily detected, and the bones were backward, the knees were everted or varused, and the dry end was increased. Wide, fragmented, trabecular thick, at the proximal end of the humerus, the distal end and the femur, humerus, ulnar distal metaphysis can have a cup-like change.
Diagnosis
Diagnosis and differential diagnosis of familial hypophosphatemic rickets in children
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.
Differential diagnosis
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 with hypocalcemia and anti-vitamin D rickets: The disease is also differentiated from hypocalcemia and anti-vitamin D rickets, the latter also known as vitamin D dependent rickets (vitamin D dependent rickets), less common, It is due to the lack of 1-hydroxylase in the kidney and the inability to synthesize 1,25-(OH)2D3. The onset time is often accompanied by muscle weakness from several months after birth. Early hand, foot and sputum can occur, blood calcium is lowered, and blood phosphorus is normal. Or slightly lower, blood chlorine 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. It is necessary to increase the amount of vitamin D to 10,000 U/d or dihydrogen. Alcohol (dihydrotachysterol, DHT) 0.2 ~ 0.5mg / d to see the effect, with 0.25 ~ 2g of 1,25-(OH) 2D3 treatment is cured, the disease is generally autosomal recessive inheritance.
3. Others: In addition, the disease must be differentiated from Fanconi syndrome and renal tubular acidosis.
