19-06-2025
Fast Five Quiz: Infant Phenylketonuria
A rare disorder, phenylketonuria (PKU) affects how patients process phenylalanine, often leading to an accumulation of this amino acid in the blood and throughout the body; this can result in intellectual disability, epilepsy, eczema, behavioral issues, and parkinsonian features. In infants, PKU usually appears asymptomatic at birth. As a result, clinicians and family must be diligent about screening and diagnosis to prevent long-term complications, with effective guidelines and dietary recommendations available as part of management.
What do you know about PKU in infants? Check your knowledge with this quiz.
Newborn screening for PKU (via blood collection from the heel) is typically performed following birth. For newborns who test positive for elevated phenylalanine, an analysis of blood and/or urine pterin metabolism is typically recommended; quantitative blood amino acid testing is also recommended, including phenylalanine-to-tyrosine ratio and complete amino acid profile.
Phenylalanine hydroxylase (PAH) genotype is then recommended to improve therapy planning and to confirm diagnosis. If no PAH variants are detected, DNAJC12 deficiency should be considered and ruled out with molecular testing. Liver function tests and cranial ultrasound are usually not implemented during this stage and are usually performed when the infant is older, if necessary.
Learn more about PKU screening.
BH4 and DNAJC12 deficiencies, as well as liver disease, are specifically recommended to be excluded in the differential diagnosis for PKU after a positive newborn screening; these cases typically will require different treatment strategies. As such, confirmatory genetic testing is recommended for patients with PKU. This can improve patient care and provide further insight into the nuances of this disease.
Learn more about PKU differential diagnosis.
Treatment for PKU should be initiated upon diagnosis and monitoring should be performed weekly through the first year of life. Additional monitoring, including clinical nutritional assessment, bone mineral density, and others, are recommended at various intervals and frequencies throughout life. These recommendations can be found in a table here.
Learn more about PKU monitoring.
The PKU dietary handbook generally recommends a phenylalanine target range of 120-360 μmol/L for infants and children up to the age of 12 years as well as for patients planning conception. This is consistent with other recommendations and recent data as well. Studies have shown that phenylalanine levels > 360 μmol/L in the first month of life are negatively correlated with IQ, and higher IQ scores are seen when patents are treated within 3 weeks compared with 4, 5, and 6-10 weeks of age. Certain guidelines classify patients into three groups: not requiring treatment (phenylalanine < 360 μmol/L), cofactor-responsive requiring treatment, and cofactor unresponsive requiring treatment.
Learn more about complications in PKU.
Breastfeeding, at any time, is generally safe in infants with PKU and can be supplemented with phenylalanine-free formula. Solely formula (that is phenylalanine-free as well) feeding is also generally safe, but limited phenylalanine (to meet the requirement for protein synthesis) must then be provided through standard infant formula. Further, researchers claim, 'there is no evidence to show that any one method leads to better blood [phenylalanine] control or has advantage with infant growth.' Certain PKU guidelines cite data indicating the safety of breastfeeding infants in both mothers with and without PKU, while also noting the importance of supplementation with medical foods and adequate monitoring of phenylalanine levels.
Total parenteral nutrition (TPN) is generally not recommended for infants during the first 6 months of life. If required, specialized TPN with reduced amounts of phenylalanine can be obtained.
Learn more about breastfeeding in PKU.
