2015年 · 第53卷第06期

Since 2007, under the leadership of group leader Professor Luo Xiaoping, deputy group leader Du Minlian, Gu Xuefan, Yang Yanling, Liang Li, Gong Chunxiu, Luo Feihong, Professor Qiu Zhengqing and other experts, the group continued to adhere to the rigorous academic style of the older generation of pediatric endocrine, genetic and metabolic experts, formulated a new orientation for the development of this major, opened up and expanded domestic and international exchanges, and made the level of this major develop rapidly.

With the change of social environment, the improvement of living standard and the strengthening of medical awareness, the number of children seeing "precocious puberty" in pediatric endocrinology clinic is increasing day by day. In order to standardize the diagnosis and treatment of central precocious puberty in children, the Endocrinology, Genetics and Metabolism Unit of Pediatrics Branch of Chinese Medical Association and the Ministry of Health have successively formulated "Guidelines for the Diagnosis and Treatment of Central (True) Precocious Puberty" and "Guidelines for the Diagnosis and Treatment of Precocious Puberty (Trial)"^[1,2]。 However, in clinical practice, there are still problems such as unclear diagnosis, irregular treatment and imperfect follow-up. In order to further standardize the diagnosis and treatment of central precocious puberty in children, the Endocrine Genetics and Metabolism Group of Pediatrics Branch of Chinese Medical Association organized experts to discuss and revised the consensus on the diagnosis and treatment of central precocious puberty in children^[3], and published in this issue. This consensus emphasizes that the following aspects should be paid attention to in the diagnosis and treatment of central precocious puberty:

With the change of disease spectrum, hereditary diseases have been paid more and more attention. The domestic meta-study found that the incidence of birth defects was basically stable between 8.4/100,000 and 10.1/100,000 from 2000 to 2006^[1]。 A study analyzed the etiology of 2 905 patients with birth defects and found that 41.0% were caused by hereditary diseases^[2]。 According to today's molecular diagnostic technology, it can still be found that a considerable part of the so-called non-genetic diseases are actually genetic diseases. Most hereditary diseases begin in infants and childhood, so pediatricians are the main body in clinical diagnosis and treatment of hereditary diseases. There are many kinds of genetic diseases. At present, there are more than 22,800 diseases or related phenotypes such as autosomal, X-linked, Y-linked and mitochondrial diseases that can be queried. The number of new diseases is increasing at a rate of 30 to 70 per month, and as many as 400 to 1,000 genetic diseases are updated every month (Online Mendelian Inheritance in Man, OMIM, http: / /omim.org/statistics/update). How to grasp the clinical diagnosis and treatment of genetic diseases under the overall situation of complexity, increasing number and new progress with each passing day is becoming an increasingly common problem.

central precocious puberty (CPP) refers to a common pediatric endocrine disease, which causes the rapid development of internal and external reproductive organs and the presentation of secondary sexual characteristics in girls before the age of 8 and boys before the age of 9 due to the early initiation of hypothalamic-pituitary-gonadal axis (HPGA) function. The incidence rate is about 1/5 000 to 1/10 000, and girls are about 5 to 10 times that of boys^[1]。 Its influence on the body is mainly as follows: premature sexual development causes early menarche in girls; Because the bone matures quickly, the bone age exceeds the actual age and the epiphysis heals early, which affects the lifetime height of children; Due to the premature development and sexual maturity of secondary sexual characteristics, it may bring corresponding psychological problems or abnormal social behavior. At present, gonadotropin-releasing hormone analogs (GnRHa) are widely used in the treatment of CPP at home and abroad. Over the past decades, the age of puberty development has been gradually advanced worldwide, and the diagnosis and treatment of CPP has attracted increasing attention. In order to standardize the diagnosis and treatment of CPP 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 as early as 2007^[2]。 In 2010, the Ministry of Health also organized the formulation of the Guidelines for the Diagnosis and Treatment of Precocious Puberty (Trial)^[3]。 However, there are still many controversial problems about the diagnosis of CPP and the clinical application of GnRHa, which need to be solved urgently. To this end, the Endocrine Genetics and Metabolism Group of the Pediatrics Branch of the Chinese Medical Association once again organized experts to discuss and reach the following consensus to guide pediatric endocrinologists in the diagnosis and treatment of CPP.

Prader-Willi syndrome (PWS, OMIM 176270), also known as hypotonia-mental retardation-gonadal development lag-obesity syndrome, Prader-Willi syndrome, is caused by Prader et al.^[1]First reported in 1956, it is the earliest genetic disease confirmed to involve genomic imprinting^[2]。 The incidence rate of different populations abroad is about 1/10 000~1/30 000, and there is a lack of epidemiological data in China^[3,4,5]。 PWS is one of the important causes of symptomatic morbid obesity. Early diagnosis and rational intervention are essential to improve children's quality of life, prevent serious complications and prolong life expectancy^{[2,3,4,5,6,7]}。 In order to fill the gap of appropriate technology for early recognition and reasonable intervention of children with PWS in China, the Endocrine Genetics and Metabolism Group of Pediatrics Branch of Chinese Medical Association put forward the following consensus on the diagnosis and treatment of PWS for reference by clinicians on the basis of extensive discussion.

congenital hyperinsulinism (CHI) refers to the condition of hypoglycemia caused by excessive insulin secretion due to various congenital causes. CHI is one of the important causes of persistent recurrent hypoglycemia in infants and children, mainly caused by abnormal insulin secretion by pancreatic islet β cells, and has a certain genetic tendency. The incidence of CHI in live births ranges from 1/30,000 to 1/50,000, while the incidence of CHI can be as high as 1/2 500 in countries and regions where intermarriage is high in relatively closed settings (e.g. the Arab region)^[1]。 Because CHI repeatedly occurs hypoglycemia, which can lead to irreversible central nervous system damage, early recognition, diagnosis and rational management are very important.

Congenital heart disease (CAD) is an important cardiovascular disease in children, which can be divided into syndromic and non-syndromic types according to the presence or absence of other congenital defects. In addition to cardiac malformations, syndromic congenital heart disease also involves congenital defects of multiple organs, accompanied by mental retardation, short stature, craniofacial development abnormalities, language development lag, skeletal abnormalities and other organ development abnormalities, etc. Its clinical consequences are extremely serious, which can lead to miscarriage, stillbirth, stillbirth and postnatal disability. Syndromic congenital heart disease is not uncommon, Karande et al.^[1]A total of 560 children with congenital heart disease from January 2011 to June 2012 were counted, of which syndromic congenital heart disease accounted for 6.4%. Miller et al.^[2]Of the 7,984 children with congenital heart disease and stillbirths caused by congenital heart disease from 1968 to 2005, 13.1% were caused by syndromic congenital heart disease caused by chromosomal abnormalities or monogenic abnormalities. With the progress of molecular biology and genetics, the research on syndromic congenital heart disease has made new developments. The current research status of syndromic congenital heart disease types, diagnosis and intervention methods is reviewed.

Progressive muscular dystrophy is common in men, mainly including Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD is caused by mutation or deletion of dystrophin gene, accounting for the vast majority of progressive muscular dystrophy, and belongs to the most common neuromuscular disease in children. The incidence in newborn boys ranges from 1/3 802 to 1/6 291^[1]。 Its main characteristics are progressive muscle dystrophy and muscle atrophy. Physical examination can show positive Gowers sign. Children are diagnosed at about 5 years old, and they lose their walking ability at 7~13 years old. After using a wheelchair, it is easy to cause scoliosis in children, and progressive cardiopulmonary dysfunction gradually appears^[2]。 The symptoms of BMD are relatively mild, with an incidence of 1/27 778 to 1/250 000^[3]。 There is no specific treatment for DMD, and glucocorticoids are currently the only recommended treatment in the world. The present situation and progress of glucocorticoid therapy for progressive muscular dystrophy are reviewed.

Randomized controlled study (RCT) is considered to be the second only to systematic review in terms of evidence. Its main advantage is that two groups of very similar patients are obtained by randomization, which is balanced and comparable, and lays a scientific foundation for demonstrating the similarities and differences between the experimental group and the control group. In clinical trial research, many RCT studies cannot be carried out due to ethical problems or research funding problems. Especially in pediatric research, most of the research objects are young children or children, and the relevant ethical issues will be more prominent when conducting RCT research. There may be confounding bias in non-RCT studies. The methods to control confounding bias include matching in the study design stage, stratification analysis in the data analysis stage or multivariate regression model. All the above methods have certain limitations, such as the ratio design needs to be considered in advance and the ratio factors should not be too many, the stratification factors should not be too many, and the stratification analysis is cumbersome. Multi-factor regression model is commonly used, but attention should be paid to the applicable conditions of regression model. The proposed propensity scoring method addresses the limitations of the above methods, which can effectively balance the confounding bias in non-RCT in the analysis and design phases, making the study design close to randomized controlled studies.