2018年 · 第56卷第06期

Turner syndrome is one of the common human chromosome abnormalities and the first described sex chromosome abnormalities. Clinically, the main manifestations are short stature, gonadal dysplasia, special facial and somatic features, and congenital cardiovascular abnormalities, kidney malformations, eye or ear abnormalities, autoimmune diseases and special neuropsychological problems, etc^[1,2,3,4]。 Its phenotype varies greatly, its karyotype is complex and diverse, and delayed diagnosis and missed diagnosis are common. Patients with Turner syndrome have different clinical problems at different ages, such as delayed growth in infants and childhood, sexual dysplasia in adolescence, and infertility in adulthood. In addition, congenital cardiovascular abnormalities are the main cause of early death in patients with Turner syndrome; The risk of comorbidities such as hearing loss and autoimmune diseases increases with age^[1,2,3,4]。 Therefore, attention should be paid to early diagnosis, comprehensive disease assessment and monitoring of patients with Turner syndrome. Standardized diagnosis and treatment are crucial to prolong the life span of patients and improve health-related quality of life.

Turner syndrome, Turner syndrome, also known as congenital ovarian hypoplasia syndrome, is caused by the complete or partial deletion of an X chromosome in all or part of somatic cells, or other structural abnormalities of the X chromosome. Its incidence ranges from 1/2 000 to 1/4 000 live-born female infants, and it is one of the common human chromosome abnormalities^[1,2,3,4]。 The typical clinical manifestations of Turner syndrome are: short stature, gonadal dysplasia, special physical features (such as neck webbing, scutellate thorax, cubitus valgus), etc. Typical Turner syndrome is easy to diagnose, but due to the large individual differences in phenotype of Turner syndrome, delayed diagnosis and missed diagnosis are more common in atypical patients. In addition, there are still some problems in the comprehensive clinical evaluation and treatment of Turner syndrome, such as lack of comprehensive evaluation of other systems and organs except short stature and gonadal dysplasia, lack of uniform recombinant human growth hormone (rhGH) treatment timing and initial therapeutic dose, lack of standardized optimal age and protocol for estrogen replacement therapy, etc^[1,2,3,4]。 In order to further improve the understanding of Turner syndrome among pediatric endocrinology, genetics and metabolism doctors, and standardize the treatment and long-term follow-up management of Turner syndrome, the Endocrine, Genetics and Metabolism Group of Pediatrics Branch of Chinese Medical Association organized experts to conduct in-depth discussions on this and reached the following consensus.

The child, 9 years old and 13 days old, was admitted to the hospital because of "rapid weight gain found for 1 year and 6 months". One year and six months before admission, the children had a significant increase in food intake without obvious trigger, strong appetite, easy hunger, less exercise, and an average weight increase of 10~15 kg/year. The child complained of easy fatigue, polyuria, an average of 10 times a day, the specific urine volume was unknown, nocturia increased, an average of 2 to 3 times/night, enuresis, Yu did not complain of discomfort, no diagnosis and treatment. Three months before admission, the child's limbs were weak, the amount of activity was significantly reduced, and he liked to stay in bed; Occasionally, the child's hands are numb, and the child's hands shake when holding objects, and the hair loss is obvious. The blood potassium was 2.5 mmol/L in the local hospital. Bilateral adrenal B-ultrasound showed bilateral adrenal enlargement, and pituitary magnetic resonance imaging showed no abnormalities. For further treatment, he was admitted to the hospital with "adrenocortical hyperplasia".

The child is a male, 5 years and 9 months old, Han nationality. He was admitted to the Department of Rheumatology and Immunology of Shenzhen Children's Hospital in May 2017 due to "repeated fever with pale complexion for more than 5 years". The child developed repeated fever more than 5 years ago (about 10 days after birth), mainly moderate to high fever, with a fever peak above 39℃, with an attack once every 2 to 3 months, each lasting for 3 to 4 days. The frequency of fever increased 3 years ago (2 years old), with an attack once every 2 to 4 weeks, each lasting for 3 to 7 days. The fever was accompanied by swelling and pain of walking joints and mobility impairment, mainly in both knees, ankles, elbows and wrists, accompanied by severe abdominal pain around the umbilical cord, vomiting, intermittent diarrhea, occasional headache, and persistent pale complexion. Other hospitals had diagnosed it as "sepsis, Kawasaki disease, chronic anemia, reactive arthritis, juvenile idiopathic arthritis", etc. The condition still recurred after treatment with anti-infection, iron supplement and non-steroidal anti-inflammatory drugs. Two years ago, he was clinically diagnosed with "acute suppurative appendicitis" and underwent laparoscopic appendectomy. Two months ago, he was diagnosed with "incomplete low intestinal obstruction". After symptomatic and supportive treatment such as fasting and gastrointestinal decompression, he improved. Five days ago, the child had fever again, accompanied by erythematous rash on the face and hands, without itching, accompanied by abdominal pain and joint swelling and pain, and was admitted to the hospital with "auto-inflammatory disease". Personal history and family history are not special.

The 41-day-old child was hospitalized in the Department of Neurology, Tianjin Children's Hospital in April 2017 due to "irritability for 6 days". The child is irritable, crying, lethargy, restless sleep, poor feeding, progressive aggravation, no convulsions, no fever, cough, vomiting and diarrhea. CT of the head performed in the local hospital showed "multiple symmetrical low-density foci in bilateral frontal, temporal, parietal and occipital subcortical areas, bilateral pons, basal ganglia areas and thalamus" (Figure 1）。 The child was the second birth of the mother, with a gestational age of 39⁺⁴Born by cesarean section in Zhou, denying history of asphyxia, birth weight 3.0 kg. Healthy parents, non-consanguineous marriage; My sister is 4 years old and developing normally. Physical examination at admission: weight 4.3 kg, head circumference 36 cm, length 52 cm, conscious, poor spirit, irritability, normal face, flat and soft anterior fontanel, no abnormalities in heart, lung and abdomen examination, poor gaze, slow auditory response, soft neck, increased muscle tone of limbs, active reflexes of bilateral knee tendons and Achilles tendons, extensibility of bilateral plantar reflexes, hug and grip reflexes (-). Auxiliary examination: electrolyte and blood gas analysis were normal, liver and kidney function were normal, 4 times blood lactate was 6.19~3.18 (normal 0.5~2.2) mmol/L, and blood ammonia was normal; Chromosomes 46, XX; No specific abnormalities were found in blood tandem mass spectrometry (MS/MS) and urine gas chromatography-mass spectrometry (GC/MS); Amino acid analysis was normal. Cerebrospinal fluid: clear in appearance, pressure 50 mmH₂O (1 mmH₂O =0.009 8 kPa), normal cells and biochemical routine, lactic acid 1.54 mmol/L. Electrocardiogram, chest X-ray and abdominal B-ultrasound were normal; EEG: Background 2~4 Hz delta and theta waves, bilateral frontal and central area spikes, sharp waves, sharp-slow waves; Cranial magnetic resonance imaging (MRI) showed patchy slightly longer T1 and long T2 signal shadows in bilateral thalamus, basal ganglia, brainstem, bilateral cerebellum and cerebral hemisphere white matter, and showed hyperintensity in diffusion-weighted (DWI) sequence (Figure 2）； Visual evoked potential (VEP) Bilateral visual P₁₀₀The brainstem auditory evoked potential (BAEP) showed abnormalities in the right peripheral segment and the left brainstem segment. There were no abnormalities in the electroneurogram and electromyogram of the limbs.

The 6-month-old child was seen in the Children's Medical Center of the People's Liberation Army General Hospital in September 2017 mainly due to "intermittent febrile convulsions". The child began to have fever-free convulsions at the age of 54 days, initially manifested as upward turning of both eyes and stiffness of the limbs, which lasted for about 30 s and resolved spontaneously, 3 to 4 times/d. Video electroencephalogram was performed to "monitor clinical attacks originating in the left occipital, posterior temporal, central and parietal midline areas". At the age of 2 months, CT of the head showed that "bilateral paraventricular white matter density was reduced", and plain scan of the head magnetic resonance imaging (MRI) showed that "bilateral frontotemporal extracerebral space was slightly wider, and no abnormal signal shadow was seen in each sequence of brain parenchyma". There were no significant abnormalities in blood amino acids, acyl carnitine and urine organic acids, and no abnormalities were found in karyotype analysis. Have taken levetiracetam oral solution with poor results. At 4.5 months of age, the attack turned into a nodding-hug-like string of spastic attacks, 5-6 strings/d, 15-16 strings/string. The EEG again showed "high irrhythm, sometimes showing an outbreak-inhibition trend during sleep, and three asymmetric spastic attacks of head deflection to the right, adduction of both upper limbs and uplift of the right lower limb were detected. At the same time, the EEG showed extensive high-amplitude spinous slow wave and slow wave combined with low-amplitude fast wave". Combination of topiramate capsules and aminohexenoic acid on the basis of levetiracetam oral solution, and adrenocorticotropic hormone (ACTH) 25 U/d combined with 25% MgSO at 6 months of age₄1 ml/ (kg·d) intravenous drip was treated for 14 days, but the efficacy was poor, and the episodes still recurred. During hospitalization, lactic acid was 1.99 mmol/L, blood ammonia was 27.9 μ mol/L, and pyruvate was 83 μ mol/L, all of which were normal. Retrospective skull MRI at 7-month-old outpatient follow-up showed "bilateral basal ganglia and thalamus long T2 signals, diffusion-weighted imaging (DWI) showed diffusion limitation" (Figure 1）。 The child was the first birth of the mother. The mother was healthy during pregnancy. She was born by cesarean section due to cephalopelvic disproportion at full term. She was asphyxiated by bruise after birth, and her Apgar score was unknown. Healthy in the neonatal period, will raise his head at 1 month old, and lag behind in development after illness. Physical examination: There were no depigmentation spots and milk caffeine spots on the skin of the whole body, high muscle tone of the limbs, and no obvious abnormalities in the remaining nervous system. Family history: Two milk caffeine spots were seen on the whole body of the child's father, the largest of which was 10 cm ×20 cm, and the child's grandfather had left facial fibroma. Panel sequencing of 534 high-throughput molecular targeting genes related to epilepsy phenotype in the children showed that there was a heterozygous variation of c.1737dupT (thymine inserted in coding region 1737) in exon 15 of proband NF1 gene, resulting in a change in amino acid position 581 (p.L581Ffs*6). Sanger sequencing validation of the proband and his parent NF1c.1737 loci confirmed that the proband and his parent NF1C.1737dupt (p.L581Ffs*6) were identical to the high-throughput molecular targeting gene sequencing results (Figure 2）。 The pathogenicity of this variant locus has not been reported in the literature, and it is not a polymorphic locus, and the frequency of occurrence in the population is extremely low. American Society of Medical Genetics and Genomics (ACMG) pathogenicity analysis as probable pathogenic. Pathogenic variants were predicted by protein prediction software MutationTaster (http: / /www.mutationtaster.org).

The 5-year-old child was admitted to the Department of Pediatrics of the Third Affiliated Hospital of Sun Yat-sen University in August 2016 because of "pale complexion for 5 years". The child was the first birth, the first birth, and was delivered naturally at full term. The birth weight was 3.4 kg, and the mother was in good health during pregnancy. Breastfeeding after birth, formula feeding at 8 months, complementary food added at 5 months. At the age of 10 months, parents found that his complexion was pale. Blood tests in many hospitals showed that he had microcyte hypochromic anemia, hemoglobin 40~50 g/L, reticulocyte ratio increased, serum iron and ferritin continued to be low, total iron binding capacity (TIBC) and serum unsaturated iron binding capacity (UIBC) were significantly increased, liver function, erythrocyte glucose-6-phosphate dehydrogenase activity, erythrocyte incubation fragility, blood lead, folic acid and vitamin B₁₂There were no abnormalities in hemoglobin electrophoresis, α/β thalassemia gene detection, Coomb test, negative hemosiderin cells in gastric juice, negative to weak positive fecal occult blood test, no abnormalities in plain chest CT scan + enhancement, abdominal B-ultrasound, total gastrointestinal barium meal, gastroscopy, colonoscopy + biopsy, bone marrow smear showed obvious erythroid hyperplasia, low color of mature red blood cells, and negative iron outside and inside bone marrow. To be diagnosed with "iron deficiency anemia", I took conventional doses of iron dextran, compound four-dimensional iron powder, polysaccharide iron complex and protein iron succinate successively. The anemia did not improve, and I was infused with red blood cell suspension twice, each time 5 ml/kg. He usually likes to eat fish, eggs and meat. He eats pig blood or liver 3 to 4 times a week, and has no heterophagia. The parents are not close relatives, and both parents and younger brother are in good health.

The child was a girl, 1 month old and 11 days old. He was admitted to the Children's Hospital affiliated to Zhejiang University in November 2016 because of "cough for more than half a month". The child was the 4th and 2nd birth, at 39⁺⁴The mother had a history of umbilical cord prolapse, the Apgar score was 1 min 1, 5 min 6, 10 min 9, and the birth weight was 2.8 kg.

Congenital lipoid adrenocortical hyperplasia (LCAH) is the rarest and most severe type of congenital adrenocortical hyperplasia (CAH), which is an autosomal recessive disease. There are currently more than 190 confirmed cases reported worldwide^[1]。 Due to the disorder of cholesterol conversion into pregnenolone, which leads to disorders in the production of steroid hormones such as glucocorticoids, mineralocorticoids and sex hormones, infants can have adrenal cortical insufficiency in the early stage. If adrenal crisis occurs without timely treatment and is life-threatening, early diagnosis and treatment is an effective way to reduce the mortality rate.

Kawasaki disease, also known as cutaneous mucosal lymph node syndrome, is an acute systemic self-limiting vasculitis, which mainly occurs in children under 5 years old. It has replaced rheumatic heart disease as one of the main pediatric acquired heart diseases. It mainly leads to permanent coronary artery injury, and may be one of the important risk factors for ischemic heart disease in adults^[1]。 microRNA (microRNA) is a non-coding small molecule RNA composed of 18-25 nucleotides. It is involved in regulating gene expression at the post-transcriptional level and participates in various biological processes such as cell differentiation, cell growth and cell death^[2]。 Studies have shown that abnormal expression of microRNA leads to changes in cell phenotype and genotype, which leads to the occurrence of inflammation, tumor and other diseases^[3]。 In recent years, the role of microRNA in the diagnosis and treatment of Kawasaki disease has attracted widespread attention of scholars at home and abroad. The abnormal expression of microRNA is closely related to Kawasaki disease, and it participates in the regulation of the occurrence, development and drug response of Kawasaki disease. The latest progress of microRNA in Kawasaki disease is reviewed to provide a basis for better diagnosis and treatment of Kawasaki disease.

Hepatitis C virus (HCV) infection is one of the major problems that threaten human health. HCV infection can cause acute and chronic liver disease and can lead to cirrhosis, hepatocellular carcinoma or liver failure. The main transmission routes of HCV include blood transfusion, blood products, organ transplantation, sexual behavior, mother-to-child vertical transmission, etc. Blood transfusion, blood products and organ transplantation were the main routes of HCV infection in children before the strict implementation of measures for screening blood products in 1992. With the screening of blood donors and the strengthening of blood product testing, mother-to-child vertical transmission has become the most common transmission mode of HCV infection in children. The global hepatitis C-related mortality rate has increased significantly in recent years. According to the Global Burden of Disease Study, the number of hepatitis C-related deaths worldwide was approximately 333,000 in 1990, rising to 499,000 in 2010, and 704,000 people worldwide died of hepatitis C in 2013^[1]。 Although direct antiviral drug therapy (DAA) has made breakthroughs, due to the hidden nature of HCV infection, safe and effective preventive HCV vaccine has not been successfully developed, human body lacks effective protective immunity after HCV infection, and mother-to-child transmission lacks effective prevention measures. Measures, and mother-to-child transmission is very harmful as the main way of HCV infection in the future. Therefore, the research work of blocking mother-to-child transmission of HCV is very important.

The Wayne diagram is a graph named after the English mathematician John Venn, used to show the relationship of sets. Wayne diagrams usually use closed circular or elliptical curves to represent a finite set. Elements within the boundary belong to the set, and elements outside the boundary do not. Wayne diagram can show the logical relationship between different sets, such as intersection, union, etc. When two circles or ellipses intersect, their intersecting parts represent the common elements of the two sets. If two circles or ellipses do not intersect, it means that the two sets have no common elements.