Management of early treated adolescents and young adults with phenylketonuria: Development of international consensus recommendations using a modified Delphi approach

Barbara K Burton; Álvaro Hermida; Amaya Bélanger-Quintana; Heather Bell; Kendra J Bjoraker; Shawn E Christ; Mitzie L Grant; Cary O Harding; Stephan C J Huijbregts; Nicola Longo; Markey C McNutt 2nd; Mina D Nguyen-Driver; André L Santos Pessoa; Júlio César Rocha; Stephanie Sacharow; Amarilis Sanchez-Valle; H Serap Sivri; Jerry Vockley; Mark Walterfang; Sarah Whittle; Ania C Muntau

doi:10.1016/j.ymgme.2022.07.012

Management of early treated adolescents and young adults with phenylketonuria: Development of international consensus recommendations using a modified Delphi approach

Mol Genet Metab. 2022 Sep-Oct;137(1-2):114-126. doi: 10.1016/j.ymgme.2022.07.012. Epub 2022 Jul 29.

Authors

Barbara K Burton¹, Álvaro Hermida², Amaya Bélanger-Quintana³, Heather Bell⁴, Kendra J Bjoraker⁵, Shawn E Christ⁶, Mitzie L Grant⁷, Cary O Harding⁸, Stephan C J Huijbregts⁹, Nicola Longo¹⁰, Markey C McNutt 2nd¹¹, Mina D Nguyen-Driver⁸, André L Santos Pessoa¹², Júlio César Rocha¹³, Stephanie Sacharow¹⁴, Amarilis Sanchez-Valle¹⁵, H Serap Sivri¹⁶, Jerry Vockley¹⁷, Mark Walterfang¹⁸, Sarah Whittle¹⁹, Ania C Muntau²⁰

Affiliations

¹ Ann and Robert H. Lurie Children's Hospital and Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Electronic address: bburton@luriechildrens.org.
² Clinical University Hospital of Santiago de Compostela, University of Santiago de Compostela, CIBERER, MetabERN, Institute of Clinical Research of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
³ Metabolic Diseases Unit, Department of Paediatrics, Ramon y Cajal Hospital, Madrid, Spain.
⁴ Fred A. Litwin Family Centre in Genetic Medicine, University Health Network and Mount Sinai Hospital, Toronto, ON, Canada.
⁵ 3:1 Neuropsychology Consultants, PLLC, Minneapolis, MN, USA.
⁶ Department of Psychological Sciences, University of Missouri, Columbia, MO, USA.
⁷ Department of Psychiatry, Drexel University College of Medicine, Philadelphia, PA, USA.
⁸ Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA.
⁹ Leiden Institute for Brain and Cognition, Leiden University, Leiden, the Netherlands.
¹⁰ Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
¹¹ McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, TX, USA.
¹² Pediatric Neurology Service, Albert Sabin Children's Hospital, University of Ceará State, Fortaleza, Ceará, Brazil.
¹³ Nutrition and Metabolism, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Portugal; Neuropsychiatry Unit, Royal Melbourne Hospital, Melbourne, VIC, Australia; Melbourne Neuropsychiatry Centre, University of Melbourne, Melbourne, VIC, Australia.
¹⁴ CINTESIS-Center for Health Technology and Services Research, NOVA Medical School, Lisboa, Portugal; Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
¹⁵ Reference Centre of Inherited Metabolic Diseases, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal.
¹⁶ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
¹⁷ Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
¹⁸ Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, USA; Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia; University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
¹⁹ Hacettepe University, Faculty of Medicine, Department of Pediatrics, Section of Pediatric Metabolism, Ankara, Turkey.
²⁰ Department of Pediatrics, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

PMID: 36027720
DOI: 10.1016/j.ymgme.2022.07.012

Abstract

Background: Early treated patients with phenylketonuria (PKU) often become lost to follow-up from adolescence onwards due to the historical focus of PKU care on the pediatric population and lack of programs facilitating the transition to adulthood. As a result, evidence on the management of adolescents and young adults with PKU is limited.

Methods: Two meetings were held with a multidisciplinary international panel of 25 experts in PKU and comorbidities frequently experienced by patients with PKU. Based on the outcomes of the first meeting, a set of statements were developed. During the second meeting, these statements were voted on for consensus generation (≥70% agreement), using a modified Delphi approach.

Results: A total of 37 consensus recommendations were developed across five areas that were deemed important in the management of adolescents and young adults with PKU: (1) general physical health, (2) mental health and neurocognitive functioning, (3) blood Phe target range, (4) PKU-specific challenges, and (5) transition to adult care. The consensus recommendations reflect the personal opinions and experiences from the participating experts supported with evidence when available. Overall, clinicians managing adolescents and young adults with PKU should be aware of the wide variety of PKU-associated comorbidities, initiating screening at an early age. In addition, management of adolescents/young adults should be a joint effort between the patient, clinical center, and parents/caregivers supporting adolescents with gradually gaining independent control of their disease during the transition to adulthood.

Conclusions: A multidisciplinary international group of experts used a modified Delphi approach to develop a set of consensus recommendations with the aim of providing guidance and offering tools to clinics to aid with supporting adolescents and young adults with PKU.

Keywords: Adolescent; Consensus recommendations; Modified Delphi; PKU; Phenylketonuria; Young adult.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Child
Consensus
Humans
Mass Screening
Phenylketonurias* / diagnosis
Young Adult