PKU is an inherited disease, so newborns are born with hyperphenylalaninemia, but because they are not fed, the blood phenylalanine and its harmful metabolites are not at high concentrations, so there are no clinical signs at birth. If a newborn is not screened for phenylketonuria, the clinical symptoms will gradually appear when the blood phenylalanine and its metabolites are gradually increased with the prolongation of feeding time. The main clinical manifestations are: 1. Growth retardation: In addition to physical growth retardation, the main manifestation is the retardation of intellectual development. The IQ is lower than that of normal infants of the same age, and can appear at 4-9 months after birth. In severe cases, the IQ is below 50, and more than 14% of children reach the level of idiocy, and the language development disorder is especially obvious. These manifestations suggest brain developmental disorders. Restriction of phenylalanine intake in newborns can prevent mental retardation, and children with severe PKU have higher blood phenylalanine concentrations than those with milder forms, so it can be assumed that mental retardation is related to phenylalanine toxicity, but the more detailed pathophysiological mechanisms remain unclear. 2. Neuropsychiatric manifestations: cerebellar malformations due to cerebral atrophy, recurrent convulsions, but decreasing with age. The muscle tone is increased and the reflexes are hyperactive. There is often excitement and restlessness, hyperactivity and abnormal behavior. 3, skin and hair manifestations: skin is often dry, prone to eczema and skin scratching syndrome. Due to the inhibition of tyrosinase, melanin synthesis is reduced, so the affected children’s hair color is light and brown. 4.Other: Due to the lack of phenylalanine hydroxylase, phenylalanine produces phenyl lactic acid and phenylacetic acid from another pathway, which is excreted from sweat and urine and has a musty odor (or rat odor). In general, the clinical presentation correlates with the type of PAH gene mutation and the severity of the clinical phenotype, with cofactor deficiency having a milder clinical phenotype than PAH protein abnormalities. The diagnosis of this disease should emphasize early diagnosis in order to obtain early treatment to avoid mental retardation. Screening for phenylketonuria must be performed in newborns to obtain an early diagnosis. 1. Screening method: The internationally accepted routine screening method is the bacterial inhibition method discovered by Guthrie. PKU screening kits are available in China. This method is used to estimate the blood phenylalanine level based on the size of the growth band of Bacillus subtilis cultured in the affected child’s blood pair. If the estimated blood phenylalanine level is 0.24 mmol/L, the test is positive. This method can be used in infants 3 to 5 days after birth. Newborns with a family history of phenylalanine should be screened more frequently in the neonatal period. 2.Phenylalanine loading test: This test can directly understand the activity of PAH. The loading dose is 0.1g/kg of oral phenylalanine for 3 days. Blood phenylalanine levels are above 1.22 mmol/L in children with classical PKU and often below 1.22 mmol/L in mild cases. The latter result suggests that these children may be hyperphenylalaninemic without PKU. Etiological diagnosis: The gene that causes phenylketonuria is the PAH gene, and the etiological diagnosis is the detection of PAH gene mutation. the detection of PAH gene mutation can not only make the etiological diagnosis for the patient, but also make the prenatal diagnosis for the fetus. There is a correlation between genotype and phenotype in most patients. The extent to which different mutation types affect PAH activity varies, so testing for mutations in the PAH gene can also be useful in determining prognosis and guiding treatment. There are many methods to detect mutations in the PAH gene, but multiplexed enzyme chain reaction (PCR) is used in combination with one or two of the latter assays, including single-strand conformation polymorphism (SSCP), restriction fragment length polymorphism (RFLP), denaturing gradient gel electrophoresis (DGGE), direct DNA sequencing, mutation site-specific oligonucleotide probes (ASO), PCR-polypropylene amine gel electrophoresis-silver staining, dideoxy fingerprinting, amplificationrefractorymutationsystem (ARMS), enzyme mismatch cleavage methods, etc. Amplified DNA can be analyzed, and SSCP analysis of RNA can be performed. Peripheral blood lymphocytes are used to analyze specimens, and polar bodies (gamete products) can be analyzed for prenatal diagnosis. Analysis of polar bodies and ASO can be used for prenatal diagnosis, and PAH genes with known mutation loci can also be examined by ASO method. There are five most common PAH gene mutations in China: R243Q, Y204C, V399V, Y356X, R413P, and these five PAH gene mutations account for 56.7%. Among the mutations, point mutations were the most common, accounting for 77.4% of the mutation types. Huang Shangzhi proposed a rapid diagnostic procedure for PAH mutations: step 1 for mutation site-specific oligonucleotide probe analysis, the diagnostic rate could reach 66%; step 2 for SSCP analysis of exon 4, the diagnostic rate increased to 80%; step 3 for detection of several common mutation sites, namely R243Q (exon 7), V339V and Y356X (exon 11) by SSCP analysis, which could make a diagnostic rate of 87%. Detection of the PTPS gene was also performed using a PCR-based method combined with the DGGE method, which allows screening of the six coding sequences of this gene and all splice sites of the PTPS gene. Both classic and cofactor deficiency-induced PKU patients have hyperphenylalaninemia, but those with hyperphenylalaninemia do not necessarily cause PKU, so PKU should be differentiated from other hyperphenylalaninemic patients. Although the cause of transient hyperphenylalaninemia is also due to a defective PAH, it is not due to a mutation in the PAH gene, but to immature PAH, resulting in an elevated blood phenylalanine concentration of 1.22 mmol/L. However, over time, the blood phenylalanine concentration can decrease to normal, and can be differentiated by following up the blood phenylalanine level. Aminotransferase hyperphenylalaninemia is caused by a deficiency of phenylalanine aminotransferase. This condition does not cause phenylketonuria, and the blood phenylalanine level is normally normal, but the blood phenylalanine concentration increases when eating a high protein diet, and the level of phenylalanine metabolites is also normal. Mild PKU can also be differentiated from cofactor-induced PKU only by genetic diagnosis and determination of blood tyrosine levels or phenylalanine loading test to determine the ratio of phenylalanine to tyrosine. Genetic diseases are difficult to treat and have unsatisfactory outcomes, making prevention even more important. Preventive measures include avoiding consanguineous marriage, promoting genetic counseling, carrier genetic testing and prenatal diagnosis and selective abortion to prevent the birth of affected children. Promote breastfeeding. Early detection of carriers of phenylketonuria and popularization of ferric chloride diapers to enable early detection and early treatment of infants who have developed the disease are important ways to prevent low intelligence.