Faculty, Staff and Student Publications

Language

English

Publication Date

1-1-2026

Journal

Molecular Genetics and Metabolism

DOI

10.1016/j.ymgme.2025.109705

PMID

41442848

Abstract

Background/objectives: Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism. If untreated, elevated blood phenylalanine (Phe) levels lead to neurological and behavioral impairments. Phe levels can be managed through a lifelong Phe-restricted diet; however, this can be challenging to maintain. Sepiapterin is an adjunct therapy for PKU that has shown efficacy in reducing blood Phe levels in both tetrahydrobiopterin (BH4)-responsive and BH4-non-responsive people with PKU in clinical trials. Practical guidance is needed for dietitians and other healthcare professionals supporting the dietary management of people with PKU who are initiating or receiving sepiapterin.

Methods: A group of international dietitians participated in a questionnaire, virtual meeting, and series of online sessions to develop globally applicable consensus recommendations to support individuals with PKU who are initiating or receiving sepiapterin treatment.

Results: The expert consensus group has issued 32 recommendations on using sepiapterin in PKU, covering the following topics: preparation, administration, response evaluation, dietary liberalization, protein substitute adjustment, healthy food choices, illness management, and if necessary, treatment cessation. These statements provide a framework to standardize care, clarify therapeutic effectiveness, guide natural protein escalation, reduce low-Phe protein substitutes, and maintain nutritional adequacy. By integrating pharmacological and dietary approaches, the guidance promotes equitable access, supports informed resource allocation, and reinforces the importance of patient-friendly education and ongoing monitoring.

Conclusions: This guidance is intended to inform clinical practice and foster consistency in the use of sepiapterin for individuals with PKU. The recommendations should evolve as new scientific evidence and growing clinical experience continue to shape best practice.

Keywords

Phenylketonurias, Humans, Pterins, Phenylalanine, Biopterins, Dietetics, Dietary restriction, Phenylketonuria, Protein, Protein substitute, Sepiapterin

Published Open-Access

yes

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