Initial results from the PHEFREE longitudinal natural history study: Cross-sectional observations in a cohort of individuals with phenylalanine hydroxylase (PAH) deficiency

Mol Genet Metab. 2024 Sep-Oct;143(1-2):108541. doi: 10.1016/j.ymgme.2024.108541. Epub 2024 Jul 22.

Abstract

Over fifty years have passed since the last large scale longitudinal study of individuals with PAH deficiency in the U.S. Since then, there have been significant changes in terms of treatment recommendations as well as treatment options. The Phenylalanine Families and Researchers Exploring Evidence (PHEFREE) Consortium was recently established to collect a more up-to-date and extensive longitudinal natural history in individuals with phenylketonuria across the lifespan. In the present paper, we describe the structure and methods of the PHEFREE longitudinal study protocol and report cross-sectional data from an initial sample of 73 individuals (5 months to 54 years of age) with PAH deficiency who have enrolled. Looking forward, the study holds the promise for advancing the field on several fronts including the validation of novel neurocognitive tools for assessment in individuals with PKU as well as evaluation of the long-term effects of changes in metabolic control (e.g., effects of Phe-lowering therapies) on outcome.

Keywords: Executive function; Motor ability; NIH toolbox; Neuropsychology; Phenylketonuria; Processing speed.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Female
  • Humans
  • Infant
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Phenylalanine Hydroxylase* / deficiency
  • Phenylalanine Hydroxylase* / genetics
  • Phenylalanine* / blood
  • Phenylalanine* / metabolism
  • Phenylketonurias* / genetics
  • Phenylketonurias* / pathology
  • Young Adult

Substances

  • Phenylalanine Hydroxylase
  • Phenylalanine