Phenylketonuria (PKU) is an amino acid metabolism disorder and an autosomal recessive genetic disease. Most patients lack phenylalanine hydroxylase in the liver, preventing the conversion of phenylalanine to tyrosine, leading to a series of metabolic abnormalities. A few children with atypical PKU lack the enzymes required for the synthesis or regeneration in the tetrahydrobiopterin metabolism process, affecting the metabolism of phenylalanine, tyrosine, and tryptophan, further exacerbating neurological damage. In summary, untreated children may suffer irreversible brain injury, resulting in intellectual disability or even seizures. The incidence rate in China is approximately 1:16,500.

bubble_chart Clinical Manifestations

1. The neonatal period is normal. A few children gradually develop symptoms such as vomiting, irritability, eczema, etc. After 3 to 4 months, intellectual retardation gradually appears, urine has a foul odor (mouse urine smell or musty smell), hair gradually turns yellow, skin becomes fair and delicate, and about 25% of children develop convulsions or infantile spasms within one year of age.
2. Intellectual disability: As age increases, intellectual disability gradually worsens. More than 95% of children have varying degrees of intellectual disability, of which 80% are grade III intellectual disability.
3. Epilepsy: Various types of epileptic seizures occur in more than 30% of affected children.

bubble_chart Auxiliary Examination

1. Blood phenylalanine levels are elevated, with normal individuals typically around 0.1 mmol/L. Affected children may exhibit levels exceeding 1.2 mmol/L. The currently implemented newborn screening for phenylketonuria (PKU) is crucial for early detection, timely treatment, and prevention of intellectual disability.
2. Both the urine ferric chloride and dinitrophenylhydrazine tests yield positive results, though these are primarily used for initial screening in older children.
3. Abnormal electroencephalogram (EEG) findings are observed in 80% of cases.
4. When atypical phenylketonuria is suspected, further analysis of urinary pterins should be conducted, or the activity of the other three enzymes involved in tetrahydrobiopterin metabolism should be measured using peripheral blood or skin fibroblast samples.
5. For children with classical phenylketonuria and their parents, DNA analysis can be performed to identify mutations in the phenylalanine hydroxylase gene, which can then inform subsequent prenatal diagnostic procedures.

bubble_chart Treatment Measures

1. For individuals with blood phenylalanine levels >1.2 mmol/L, phenylalanine intake should be restricted. Low or phenylalanine-free milk formulas should be used to maintain phenylalanine levels between 0.3–0.6 mmol/L. Treatment should ideally begin as early as possible, before 3 months of age. While treatment initiated after 1 year of age may improve seizure symptoms, intellectual disability is irreversible. Phenylalanine-restricted diets should be continued until 6–10 years of age. When infants consume low or phenylalanine-free milk formulas, an appropriate amount of breast milk should be added to prevent excessively low phenylalanine levels, as breast milk contains only one-fourth the phenylalanine found in cow's milk. High-protein foods such as meat, eggs, and legumes are rich in phenylalanine, while plant-based foods have relatively lower levels. During treatment, regular follow-up monitoring of blood phenylalanine levels should be conducted based on age to adjust dietary phenylalanine intake, while also observing growth and development.
2. Currently, therapeutic milk formulas for phenylketonuria (PKU) are available. Therefore, regions with the necessary resources should implement newborn screening for PKU to enable early detection, early treatment, and prevention of intellectual disability.