Global prevalence of classic phenylketonuria based on Neonatal Screening Program Data: systematic review and meta-analysis

Phenylketonuria is a disease caused by congenital defects in phenylalanine metabolism that leads to irreversible nerve cell damage. However, its detection in the early days of life can reduce its severity. Thus, many countries have started disease screening programs for neonates. The present study aimed to determine the world-wide prevalence of classic phenylketonuria using the data of neonatal screening studies. The PubMed, Web of Sciences, Sciences Direct, ProQuest, and Scopus databases were searched for related articles. Article quality was evaluated using the Joanna Briggs Institute Critical Appraisal Evaluation Checklist. A random effect was used to calculate the pooled prevalence, and a phenylketonuria prevalence per 100,000 neonates was reported. A total of 53 studies with 119,152,905 participants conducted in 1964-2017 were included in this systematic review. The highest prevalence (38.13) was reported in Turkey, while the lowest (0.3) in Thailand. A total of 46 studies were entered into the metaanalysis for pooled prevalence estimation. The overall worldwide prevalence of the disease is 6.002 per 100,000 neonates (95% confidence interval, 5.07-6.93). The metaregression test showed high heterogeneity in the worldwide disease prevalence (I-2=99%). Heterogeneity in the worldwide prevalence of phenylketonuria is high, possibly due to differences in factors affecting the disease, such as consanguineous marriages and genetic reserves in different countries, study performance, diagnostic tests, cutoff points, and sample size.