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Newborn phenylalanine/tyrosine metabolism. Implications for screening for phenylketonuria
Insights
Newborn screening for phenylketonuria (PKU) sensitivity is debated. Retesting infants within 1-2 weeks improves detection, as phenylalanine levels change with age, making later screening more accurate.
Area of Science:
- Biochemistry
- Genetics
- Neonatal Medicine
Background:
- Controversy exists regarding the sensitivity of newborn screening for phenylketonuria (PKU).
- A recommendation has been made for retesting infants discharged within 24 hours of birth at 1-2 weeks of age.
Purpose of the Study:
- To analyze data to address the controversy surrounding newborn screening sensitivity for PKU.
- To evaluate the impact of infant age on phenylalanine (Phe) concentrations and screening accuracy.
Main Methods:
- Analysis of cord blood samples, phenylalanine tolerance tests at 3 days, and sequential plasma Phe levels in siblings of PKU cases.
- Inclusion of data from existing literature for comprehensive analysis.
- Development of predictive equations to assess screening sensitivity over time.
Main Results:
- Normal and heterozygous infants show decreasing Phe concentrations with age.
- Infants with PKU or PKU variants exhibit increasing Phe concentrations at varying rates.
- Screening test sensitivity increases with age; a 4 mg/dL critical value is satisfactory after 18 hours.
Conclusions:
- Newborn screening for PKU can be made more sensitive by considering infant age.
- A modified Guthrie test with a 3 mg/dL critical value could offer consistent sensitivity at any age.
- Retesting infants, particularly those discharged early, enhances diagnostic accuracy for PKU.
Abstract:
Controversy over the sensitivity of newborn screening for phenylketonuria (PKU) has recently led to the specific recommendation that infants discharged within the first 24 hours of life be routinely retested at 1 to 2 weeks of age. To address this controversy, data from cord blood samples, phenylalanine (Phe) tolerance tests at 3 days of age, and sequential plasma Phe determinations in six siblings of known cases of PKU or hyperphenylalaninemia were analyzed, along with data from the literature. These analyses showed that normal and probably heterozygous infants decrease their Phe concentrations with age, while infants with PKU or PKU variants increase their Phe concentrations with age but at varying rates. Predictive equations showed that the sensitivity of the screening test rapidly increases with age, so that the usual critical value of 4 mg/dL is satisfactory for suspecting PKU after 18 hours of age. A critical value of 3 mg/dL would be equally satisfactory at any age, if the Guthrie test were appropriately modified to include a 3-mg/dL standard.