Improving the Diagnosis of Phenylketonuria by Using a Machine Learning–Based Screening Model of Neonatal MRM Data

Phenylketonuria (PKU) is a common genetic metabolic disorder that affects the infant's nerve development and manifests as abnormal behavior and developmental delay as the child grows. Currently, a triple–quadrupole mass spectrometer (TQ-MS) is a common high-accuracy clinical PKU screening method. However, there is high false-positive rate associated with this modality, and its reduction can provide a diagnostic and economic benefit to both pediatric patients and health providers. Machine learning methods have the advantage of utilizing high-dimensional and complex features, which can be obtained from the patient's metabolic patterns and interrogated for clinically relevant knowledge. In this study, using TQ-MS screening data of more than 600,000 patients collected at the Newborn Screening Center of Shanghai Children's Hospital, we derived a dataset containing 256 PKU-suspected cases. We then developed a machine learning logistic regression analysis model with the aim to minimize false-positive rates in the results of the initial PKU test. The model attained a 95–100% sensitivity, the specificity was improved 53.14%, and positive predictive value increased from 19.14 to 32.16%. Our study shows that machine learning models may be used as a pediatric diagnosis aid tool to reduce the number of suspected cases and to help eliminate patient recall. Our study can serve as a future reference for the selection and evaluation of computational screening methods.