International Survey on Phenylketonuria Newborn Screening.

Area of Science:

• Biochemistry
• Genetics
• Public Health

Background:

• Newborn screening for Phenylketonuria (PKU) is crucial for early detection and dietary intervention, preventing severe neurological impairment.
• Despite its long-standing effectiveness, PKU screening, diagnostic, and treatment protocols exhibit significant international variability.

Purpose of the Study:

• To evaluate and compare international newborn screening practices for Phenylketonuria, focusing on laboratory methodologies.
• To identify areas of divergence and convergence in current PKU screening protocols across different countries.

Main Methods:

• A survey was distributed to assess laboratory aspects of PKU newborn screening systems.
• Data from 24 completed surveys across 23 countries were analyzed, examining parameters like sampling age, analytical techniques, cutoff values, and confirmatory methods.

Main Results:

• Most centers utilize tandem mass spectrometry with non-derivatized kits for phenylalanine (Phe) measurement, typically with a screening cutoff (COV) around 120 µmol/L.
• Confirmatory methods commonly include genetic analysis and amino acid analysis, with a dietary therapy initiation cutoff generally set at 360 µmol/L Phe.
• Significant variations were observed in sampling age ranges, screening COVs, use of additional parameters like the Phe/tyrosine ratio, and inclusion of other metabolic disorder screenings.

Conclusions:

• While core methodologies for PKU newborn screening are shared, substantial practice variations exist globally.
• The findings suggest an opportunity to establish a best practice guideline for PKU newborn screening and post-screening parameters to ensure more uniform and effective patient management.