2011年 · 第49卷第06期

Example 1Female, 3 years and 5 months old, came to the screening clinic of our hospital because "thyroid stimulating hormone (TSH) was increased for 2 days in neonatal disease screening". There were no complaints of discomfort. 1st birth, 1st birth, gestational age 40 weeks, natural delivery, birth weight 2.4 kg. A family genetic history is denied. Physical examination revealed grade II/6 systolic murmur in the precordial area. Thyroid function test: TSH>75 mU/L, total tetraiodothyronine (T₄), free tetraiodothyronine (FT₄) decreased by 41.2 nmol/L, 6.5 pmol/L, and total triiodothyronine (T₃) and free triiodothyronine (FT₃) were all normal and thyroid antibodies were all negative. B-ultrasound scan showed no abnormalities in thyroid shape and position. Color Doppler examination of the heart revealed congenital heart disease (atrial septal defect) with a diameter of 0.3 cm. He was diagnosed as congenital hypothyroidism (CH) and was given oral treatment with levothyroxine sodium tablets (Euthyrox) 6 μ g/ (kg·d). During the follow-up, it was found that the children's physique and intellectual development were lagging behind, and gradually showed special faces. Physical examination at 1 year of age: weight 6.5 kg (P₃～P₁₀), height 71.5 cm (P₂₅), head circumference 42 cm (P₃～P₁₀), special face (full periorbital, flat nose bridge, middle-length, thick lips, protruding ears, small teeth, uneven arrangement), grade II/6 systolic murmur can still be heard in the precordial area, low muscle tone of the limbs, large joint mobility, unsteady sitting alone, unable to crawl, unable to call "mother". Laboratory tests showed no abnormalities. Abdominal B-ultrasound: the shape of both kidneys is small. fluorescence in situ hybridization (FISH) revealed a 7q11.23 microdeletion (Figure 1，Figure 2)。 Coaching exercise and language training; Euthyrox was gradually reduced to 1/4 tablets daily, and thyroid function was monitored normally. It was discontinued at age 2. At present, the thyroid function is normal, the physical and intellectual development is backward, and the body weight is 14.5 kg (P₂₅～P₅₀), height 94 cm (P₁₀～P₂₅), head circumference 45 cm (P₃～P₁₀)； lagging bone age (equivalent to 2 years); Bayley test: Intelligence scale coarse score 100, exercise scale coarse score 43; Intellectual development index<50； Motor development index<50。

A 13-year-old male was admitted to the hospital mainly for "polydipsia and polyuria for 7 years, vomiting, anorexia and mental poverty for 3 days". Seven years before admission, the child's water consumption increased without inducement, and the daily water consumption was between 4200 and 6000 ml. He liked to drink cold water, and his urine volume also increased. The urine color was as clear as water, and his urine volume was equivalent to the water consumption, and he had enuresis from time to time. Deny history of headache, vomiting, coma, deny history of cranial trauma. He has been diagnosed and treated in many hospitals, considering "psychotic polydipsia" and "diabetes insipidus", and was taken irregularly with traditional Chinese medicine (specifically unknown) and vasopressin acetate, but the curative effect was not good; Three days ago, the child vomited after catching a cold, which was not a jet. He vomited 3 to 4 times on the first day of the illness, and then gradually worsened. He vomited immediately after eating, which was the contents of the stomach. He could not eat, and his spirit became worse. He came to our hospital for treatment and was admitted to the hospital. There are no convulsions or diarrhea when the disease comes; Deny history of unclean eating and exposure to poisons. The child was the first birth, first birth, full-term natural delivery, no abnormalities in birth history, and the physical and intellectual development was the same as that of normal children of the same age. Parents, grandparents and maternal grandparents are not close relatives married, and their parents are in good health.

The child was a 9-year-old male. Admitted for 3 years due to swollen joints. Three years ago, the parents of the child found that the joints of his limbs were swollen. At that time, there was no fever, rash and joint pain, no obvious restriction of joint movement, no oliguria and general edema. During this period, ESR, ASO and RF were negative, and the knee joint effusion was exudate, which was not paid attention to. The swelling of each joint increased year by year, and no special treatment was given. The vaccination was performed according to the procedure, there was no history of tuberculosis contact, the parents were not close relatives married, and there were no patients with similar diseases in the family.

A 12-year-old male was admitted to the hospital with the main complaint of "intermittent melena and pale complexion for more than 8 years". Eight years ago, the child developed melena after fever (body temperature 37.3~37.4 ℃), accompanied by paroxysmal pain around the umbilical cord, and then appeared pale. He was diagnosed as "gastrointestinal bleeding" in an outside hospital with unknown cause. He intermittently took "omeprazole and Yunnan Baiyao" for treatment, but the effect was poor. Later, he went to many hospitals for gastroscopy, colonoscopy, abdominal CT and other examinations, but none of them were diagnosed. In the past month, the child developed melena and pale again, and came to the hospital for treatment. Physical examination at 36.9 ℃, clear consciousness, poor spirit, severe anemia, unpalpable swelling of superficial lymph nodes, coarse breathing sounds in both lungs, heart rate 100 beats/min, uniform rhythm, systolic grade II/6 murmur in the precordial area, soft abdomen, not reaching the liver and spleen under the costs, and no edema in both lower limbs. Auxiliary examination: Blood routine WBC 3.7×10⁹/L, RBC 1.81×10¹²/L, HB 28 g/L, PLT 363×10⁹/L, normal coagulation function, fecal occult blood test (+ +). Initial diagnosis of gastrointestinal bleeding after admission, supportive treatment such as correction of anemia and further improvement of relevant examinations were given. Color Doppler ultrasound showed: thickening of liver parenchyma structure, hyperechoic left lateral lobe of liver, and splenomegaly; Bone marrow cytology examination showed: iron deficiency bone marrow image; Gastrointestinal isotope emission computer-assisted tomography (ECT) showed that abdominal ectopic gastric mucosa was negative; Intestinal ECT (^99mTC-RBC) showed that irregular abnormal concentration of radioactivity was observed at the level of the lower pole of the kidney on the median iliac vessel bifurcation of the abdominal cavity, and the radioactivity increased with time, and the position was relatively fixed (Figure 1)； 64-slice spiral CT virtual colonoscopy showed that irregular soft tissue masses were seen in the jejunal segment at the level of the middle and lower kidney poles, with a size of about 2.0 cm ×3.5 cm. There was no obvious enhancement in the arterial phase, with a CT value of about 30 HU, and uniform and obvious enhancement in the portal vein phase, with a CT value of about 72 HU. Multiple punctate high-density calcifications were seen in the mass, considering the intestinal occupation (Figure 2), and then transferred to surgical laparotomy showed that during the operation, there was a dark red mass of about 5.0 cm ×3.0 cm ×3.0 cm in size to the mesangial margin of the small intestine about 5 cm away from the Trigger's ligament, which was of medium quality and nodular shape, and partial jejunectomy and intestinal anastomosis were performed. Postoperative pathology showed: (jejunum) cavernous hemangioma with hemorrhagic calcification, chronic inflammation at both ends of the intestine (Figure 3)。 The child recovered well after operation.

congenital hypothyroidism (congenital hypothyroidism) is one of the common pediatric endocrine diseases that cause children's intellectual development and physical development to lag, and it is also a preventable and treatable disease. Because children with congenital hypothyroidism may have no specific clinical symptoms or mild symptoms in the neonatal period, group screening of neonates is the main method to detect congenital hypothyroidism early. Screening for neonatal congenital hypothyroidism has been carried out in China since 1981. At present, the national screening coverage rate has exceeded 60%, and the incidence rate is about 1/2050^[1,2,3,4]。 With the further promotion of neonatal disease screening nationwide, the number of medical institutions and specialists who diagnose and treat congenital hypothyroidism is increasing. In order to standardize the diagnosis and treatment of diseases, the Ministry of Health promulgated the Technical Specifications for Screening of Neonatal Diseases (2010 Edition) in 2010^[5]。 On the basis of this standard framework, this paper puts forward further operational consensus for neonatal screening, screening result analysis, diagnosis and treatment, follow-up, etc.

congenital nephrotic syndrome usually refers to a nephrotic syndrome that onsets within 3 months after birth, and its clinical manifestations meet the diagnostic criteria of nephrotic syndrome with massive proteinuria, hypoalbuminemia, severe edema and hypercholesterolemia. According to the etiology, it can be divided into primary (hereditary) and secondary (non-hereditary). primary is caused by mutations in the coding genes of multiple glomerular filtration barrier constituent proteins or other related genes, and secondary is mostly caused by intrauterine infection or maternal disease (Table 1)^[1]。

Precocious puberty is a common clinical endocrine disease in children, and its physiological and psychological influence and standardized diagnosis and treatment have been a hot spot in the field of pediatric endocrine research. In recent years, childhood precocious puberty caused by various environmental estrogens has also attracted people's attention, and the incident of "precocious puberty caused by milk powder in girls" in 2010 has made childhood precocious puberty the focus of widespread social attention. The occurrence of this incident also reflects the insufficient understanding of the disease by non-pediatric endocrinologists. In order to standardize the diagnosis and treatment of precocious puberty in children, the Endocrine Genetics and Metabolism Group of Pediatrics Branch of Chinese Medical Association formulated the Guidelines for the Diagnosis and Treatment of Central (True) Precocious Puberty in 2007^[1]。 After the "milk powder incident", the Ministry of Health also organized and formulated the "Guidelines for Diagnosis and Treatment of Precocious Puberty (Trial)" in time^[2]。 However, there are still many unsatisfactory points in the clinical diagnosis and treatment of precocious puberty. This article intends to explain the problems that should be paid attention to in the diagnosis and treatment of precocious puberty in children from the clinical practical angle.

The second section of Chapter 13 of Clinical Genetic Counseling published in 2007 is "Maternal Metabolic Congenital Malformations"^[1]。 Its concept refers to the damage to the embryo or fetus caused by abnormal metabolites in the body of a pregnant woman before conception or during pregnancy; Excludes birth defects caused by the transmission of genetic information. Typical diseases listed include maternal diabetics syndrome (MDS), maternal phenylketonuria (MPKU), fetal alcohol syndrome (FAS), etc^[2,3,4]。 Take MPKU as an example: it does not mean that the fetus itself suffers from PKU, a genetic disease, but because the pregnant woman suffers from PKU before pregnancy, and the condition is not controlled after treatment or treatment, phenylalanine in the maternal blood accumulates abnormally, resulting in intrauterine fetal brain damage, which is characterized by mental retardation. Therefore, monitoring the blood phenylalanine level of pregnant women with PKU has long been one of the three categories of indications clearly recommended in the application guidelines of mass spectrometry in developed countries^[5]。

Measles is a common and primary eruptive infectious disease in children. It is spread to other susceptible people by respiratory droplet inhalation or contact with polluted surrounding environment. It is highly infectious and has many complications. It is periodic before the vaccine is applied, and the mortality rate is extremely high. So far, there is no anti-measles virus drug. From 1956 to 1965, the average annual incidence rate of measles in China reached 766/100,000, and the mortality rate was as high as 39.7/100,000. Since 1987, the incidence of measles has been controlled at about 10/100,000, mainly sporadic, and there are small local epidemics^[1]。

The repair of nerve cell damage has been a major problem in the international biomedical community, which has not been effectively solved for a long time. Neonatal brain injury is one of the main causes of death and disability in children. Although a series of long-term intervention studies have been conducted at home and abroad, the clinical efficacy has been unsatisfactory. In recent years, the basic research of neural stem cells has made great progress. Studies have shown that neural stem cell transplantation has a good effect on neonatal brain injury, which brings hope for the treatment of neonatal brain injury. This article is the first in the world to report the application of neural stem cell transplantation in the treatment of neonatal brain injury children. These cases of brain injury are very serious, after neural stem cell transplantation treatment, some curative effects have been achieved. This is a pioneering clinical application research of new technology, which is of great significance.

Alport syndrome (AS) is one of the most common hereditary kidney diseases. The main clinical manifestations are hematuria and progressive renal dysfunction, accompanied by sensorineural deafness and ocular abnormalities. AS is a genetically heterogeneous disease, and three genetic modes have been confirmed at present: X-linked dominant Alport syndrome (XLAS) is the most common, accounting for about 80% to 85%, becauseCOL4A5Genetic mutations orCOL4A5AndCOL4A6Caused by two gene mutations; Autosomal recessive Alport syndrome (ARAS) accounts for about 15%, and autosomal dominant Alport syndrome (ADAS) is very rare, both due toCOL4A3OrCOL4A4Caused by gene mutation^[1,2]。 We have performed genetic diagnosis on many AS families in our previous studies^[3]And carried out prenatal genetic diagnosis of AS in China^[4]。 Here, we discuss the methods of prenatal genetic diagnosis and the problems that need attention in combination with several families of prenatal genetic diagnosis with different genotypes of AS.