Neonatal Screening In Portugal: The Results of a Retrospective Cohort Study of 113 Adult PKU Patients

Esmeralda Martins ^2,3,4 Manuela Almeida ^1,2,3,4 Celia Soares ^1,2,3,4 Anabela Bandeira ^2,3,4 Joana Correia ^2,3,4 Ana Cunha ^2,3,4 Sara Rocha ^2,3,4 Arlindo Guimas ^2,3,4 Rosa Ribeiro ^2,3,4 Rute Martins ^2,3,4 Vania Magalhaes ^1,2 Sofia Pinto ^1,2 Ana Fortuna ^1,2,3,4 Carla Carmona ^1,2,3,4

¹Centro Genética Médica, Centro Hospitalar Universitário de Santo António, Portugal
²Centro de Referência para as Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário de Santo António, Portugal
³Unidade de Multidisciplinar de Investigação Biomédica, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal
⁴Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional, Universidade do Porto, Portugal

BACKGROUND: Phenylketonuria (PKU) is the most common inborn error of protein metabolism in Europe whose consequences are preventable. There was a paradigm shift in the follow-up of these patients in 1993 at our Reference Centre: the definition of safe Phe levels ≤ 6 mg/dL up to the age of 12 years, more diversity of special low protein foods, freely available, and more regular follow-up by a multidisciplinary team. Changes observed in the results on the quality of dietetic control (QDC) and cognitive outcomes were used to evaluate the long-term follow-up of these patients.

METHODS: This retrospective cohort study involved 113 adult early-diagnosed PKU patients without additional disorders. Three groups were considered based on PKU classification, hyperphenylalaninemias (HPA), mild and classical, and characterised in terms of QDC and mental health.

RESULTS: There were significant differences between the three groups in their last global IQ values, with classical PKU patients having lower mean IQ global values, worse QDC, and a higher percentage of individuals with adapted curriculum or special education and more severe comorbidities. After 1993, we observed a clear improvement in the lifelong QDC in mild and classical PKU patients, with an impact on their cognitive performance and quality of life.

DISCUSSION: These results point to the need for a regular psychological follow-up in the mild and classical forms of the disease to optimise their QDC and cognitive outcomes, even in adulthood. Being born after 1993 marks a paradigm shift in the performance of PKU patients in their quality of metabolic control. It is hypothesised that the definition of safe Phe levels ≤ 6 mg/dL up to the age of 12 years, with more diversity of special low protein foods, available for free, and the establishment of a more proactive and regular follow-up by the multidisciplinary team of these patients contributed to this improvement.