Inherited metabolic disorders (inherited metabolic disorders), also known as inborn errors of metabolism (inborn errors of metabolism, IEM), is due to genetic mutations that lead to a variety of abnormalities in the synthesis, metabolism, transport and storage of biochemical substances in the body. It includes abnormalities in sugar, amino acid and organic acid metabolism, urea cycle disorders, purine metabolism, metal metabolism, lysosomal diseases, mitochondrial diseases, peroxisomal diseases, and abnormalities in porphyrin, bilirubin and erythrocyte metabolism, etc. The total morbidity rate of IEM is quite high, and it often leads to progressive and irreversible neurological damages, which can lead to mental retardation. Newborn screening for IEM and screening of high-risk infants can reduce disability and death and improve the quality of population health. 1, genetic metabolic defects newborn screening (1) newborn screening (neonatal screening) refers to the newborn period for some serious harm to some congenital diseases, genetic birth defects for group screening and early diagnosis and treatment, to avoid or reduce the intellectual disability, improve the quality of health of the birth population of special health care technology. Newborn screening of congenital hereditary birth defects in the neonatal period and even in small infants often lack of specific symptoms, once the symptoms have formed irreversible damage, the loss of a good opportunity for treatment; and in the early neonatal blood has been biochemical metabolism and other changes in the early days of the newborn, the experimental method can be made to make an early diagnosis. (2) How to implement newborn screening The implementation of screening technology services include the establishment of a screening network, screening technology, quality control system and information system. The service procedures include newborn screening health education and the principle of informed choice → filter paper dried blood film collection → blood film specimen delivery to the screening center as soon as possible → laboratory screening test → identification of positive screening, positive report and recall → case diagnosis and treatment → tracking and follow-up → screening information statistics and reporting. The above service procedures can be divided into technical aspects such as collection of screening blood samples, laboratory testing, early diagnosis and treatment of disease, service aspects such as education and mobilization, delivery of blood samples, recall of positives, and management aspects such as organization and management, quality control, and information services. The technical, service and management measures should be organically linked and optimized in order to implement newborn screening with low consumption and high efficiency, and fully meet the Ministry of Health’s “Newborn Disease Screening Technical Specification”. (3) More than 40 years of international screening practice has proved that newborn screening can provide early diagnosis and treatment of IEM, maintain normal brain and intellectual development, and prevent intellectual disability. Improving the health quality of the birth population through group screening services. In Guangzhou, a total of 945,372 newborns were screened for congenital hypothyroidism (CH), phenylketonuria (PKU), and glucose-6-phosphate dehydrogenase (G6PD) deficiency from April 1989 to June 2007. There were 331 cases of CH, 29 cases of PHPA, and 39,700 cases of G6PD deficiency.The prevalence of CH was 1:2856, PHPA 1:32,599, and G6PD deficiency amounted to 1:23.81, with an overall prevalence of 4.24%. The effective rate of early diagnosis and treatment of CH and PHPA in the screening group was 99.2%. (4) Social and economic benefits In Guangzhou, for example, due to the implementation of newborn screening, children born in Guangzhou with hypothyroidism, PKU and G6PD deficiency have avoided the fate of intellectual disability, and realized the goal of preventing birth defects without disability, providing a strong guarantee of the quality of the health of the population at birth. Since the establishment of Guangzhou Newborn Screening Center, 377 cases of children with intellectual disabilities have been prevented. Preventing one case of children with intellectual disabilities can reduce the economic loss for the society by at least 1 million yuan, which can save 40 million yuan of economic loss for the city of Guangzhou every year, and the cumulative economic loss has been saved for nearly 400 million yuan or more. By the end of 2007, the total number of newborns screened in Guangdong Province had reached 3 million, and a total of 1,500 cases of hypothyroidism and PKU had been treated and prevented, saving the province at least 1.5 billion RMB in economic losses. If the province’s 1 million/year newborns are screened for CH and PKU, according to the morbidity rate, at least 500 cases of CH and PKU can be prevented each year, and the economic loss can be recovered by 500 million RMB. The amount of nationwide statistics is even greater. (5) China’s newborn screening status Since 1981, according to relevant statistics, the country has screened 15 million newborns, screened and detected a total of 8,000 cases of two metabolic diseases, CH and PKU, the incidence rate of CH is 1:2033, PKU 1:11,680. according to incomplete statistics, the country in 2006, a total of more than 3 million newborns screened, according to the number of births of 18 million, the rate of newborn screening is 17%, and the rate of newborn screening is 1:2033. The screening rate of newborns is 17%. It can be seen that China’s newborn disease screening less disease, screening regional coverage, newborn screening rate is still at a low level. It is imperative that all parts of the country, all relevant departments and screening institutions to speed up the promotion and popularization, pay attention to screening standards, strengthen laboratory quality management and overall quality management, and strive to expand new programs, so that newborn screening for the prevention and treatment of IEM and improve the quality of the population to play a greater role. (6) Tandem mass spectrometry and neonatal metabolic disease screening On the other hand, China’s genetic metabolic disease screening or diagnosis work carried out earlier, based on a better, technologically advanced screening units such as the Shanghai Institute of Pediatrics, Guangzhou Women’s and Children’s Medical Center, Children’s Hospital of Zhejiang Province, etc., has established tandem mass spectrometry screening and detection technology, which can be screened for up to 40 types of IEM, for the investment of less manpower and resources, and the improvement of the quality of population, and the improvement of the quality of the population. This has created conditions for more IEM control and improved screening efficiency. Currently, tandem mass spectrometry is routinely used to screen for 23 diseases in various states of the United States, expanding the number of first-line screening diseases to 29. Tandem mass spectrometry is a very suitable and potential means of newborn IEM screening. Tandem mass spectrometry screening of high-risk infants with inherited metabolic defects (1) Clinical characteristics of inherited metabolic defects IEM are diverse and complex, or chronic progressive onset, or sudden onset when there are triggers, involving the whole body, and most often causing progressive and irreversible neurological damage, leading to mental retardation, or leading to the dysfunction of major organs, with a high rate of death and disability. The treatment of some inherited metabolic defects is not very complicated, such as classic phenylketonuria, maple diabetes mellitus, Citrin deficiency disease, etc. Diet control therapy can be effective. Urea cycle disorders often improve with correction of metabolic acidosis, lowering of blood ammonia concentrations and regulation of the balance of relevant amino acids in the body. Hypoglycemic crisis due to insufficient energy supply can be prevented by early diagnosis of medium-chain acyl-coenzyme A dehydrogenase deficiency (MCAD) by screening and uninterrupted sugar supplementation to prevent starvation. Treatment of biotinidase deficiency with biotin and vitamin B12 for vitamin B12-responsive methylmalonic acidemia can even be dramatically effective. This shows that IEM focuses on diagnosis. (2) Diagnostic methods for hereditary metabolic defects In the past, due to insufficient clinical awareness and lack of testing methods, IEM diagnosis used to be a difficult clinical problem. In recent years, with the popularization of routine biochemical tests, ultrasound, nuclear magnetic resonance and neuromuscular electrophysiological tests, and the application of specific biochemical tests such as tandem mass spectrometry (MS-MS) and gas chromatography/mass spectrometry (GC-MS), the body can be analyzed for glucose, ammonia, ketones, acid-base balance, electrolytes, amino acids, organic acids, fatty acids, and free meat, etc. in the blood or urine by means of routine biochemical and specific biochemical tests, Metabolic analysis and metabolic evaluation of organic acids, fatty acids, free carnitine and acylcarnitines, and other substances at various levels. As well as the application of cellular enzymology and molecular biology techniques in the diagnosis of hereditary metabolic defective diseases, we provide a scientific basis for the clinical diagnosis of hereditary metabolic defective diseases. MS-MS and GC-MS technology due to simple sampling, easy delivery and high-throughput detection at the same time and become a routine means of IEM screening of high-risk infants, especially the use of filter paper dried blood spot as a sample of the MS-MS instrument is suitable for both newborn screening and high-risk screening. (3) Tandem mass spectrometry screening of children at risk for inherited metabolic defects Tandem mass spectrometry screening should be routinely performed in children with high-risk clinical conditions for IEM. The analytical process of tandem mass spectrometry includes ionization of the molecules to be measured, separation of the ions according to the different mass-to-charge ratios (m/z), and detection of the ions by various scanning modes, so as to qualitatively and quantitatively characterize the molecules of the substances to be measured. Tandem mass spectrometry can be used to qualitatively and quantitatively detect dozens of metabolic substances in the body, analyze the metabolic state of the body and its abnormal changes, identify abnormal indicators, evaluate the metabolism of amino acids, organic acids, fatty acids, free carnitine and acylcarnitines, and perform high-risk screening and clinical testing for 40 types of IEMs. 2007, the Newborn Screening Center of the Guangzhou Women’s and Children’s Medical Center used API 3200 to screen 7 IEMs. In 2007, the Newborn Screening Center of Guangzhou Women’s and Children’s Medical Center used API 3200 tandem mass spectrometry to screen 748 high-risk infants for IEMs, and 29 types of IEMs were detected, with an overall detection rate of 12.70%. Currently, newborn screening for 29 IEMs is conducted in all states in the United States, of which 23 are performed by tandem mass spectrometry. Tandem mass spectrometry screening of high-risk infants and newborn screening are performed using filter paper dried blood specimens, which are usually collected on an empty stomach, dried for 3 h, and then couriered or delivered to a screening center for testing. Detailed clinical information should be provided for metabolic analysis. The results may be more clinically significant when blood is collected during the acute onset of IEM due to triggers. Those who are positive for IEM should be re-tested and urine GC-MS analysis should be performed to complement MS-MS analysis. Whenever possible, samples should be retained for enzymatic and DNA analysis.