Impact Of A Phe-Restricted Diet On Gut Health In Children With PKU

Summary

Phenylketonuria (PKU) is an inherited disorder of phenylalanine (Phe) metabolism. The mainstay of treatment is a Phe-restricted diet, which aims to maintain blood Phe concentrations within the recommended range and prevent neurological complications. Some individuals with PKU respond to pharmacological treatments, including sapropterin, a synthetic form of tetrahydrobiopterin (BH4), or sepiapterin. These treatments may increase Phe tolerance and allow a less restrictive diet.

Diet is an important determinant of gut microbiota composition and function. However, the effects of the Phe-restricted diet and pharmacologically enabled dietary relaxation on the gut microbiota in PKU remain poorly understood.

This observational study includes children and adolescents with PKU aged 3-17 years attending Birmingham Children's Hospital. Participants include those managed exclusively with a Phe-restricted diet, those receiving sapropterin, and those receiving sepiapterin. One healthy household control is recruited for each participant with PKU.

Faecal samples are collected for shotgun metagenomic sequencing and metabolite profiling. Dietary intake, gastrointestinal symptoms, stool characteristics, clinical information, and PKU treatment are also assessed.

The study investigates whether gut microbiota composition, microbial functional potential, and faecal metabolite profiles differ between participants managed with a Phe-restricted diet, those receiving pharmacological treatment, and healthy household controls. The findings may improve understanding of the relationships between PKU treatment, dietary restriction, gastrointestinal health, and the gut microbiome and may inform future nutritional strategies for individuals with PKU.

Conditions

• Phenylketonuria

Interventions

OTHER

Phenylalanine-restricted diet alone

Participants are managed with a phenylalanine-restricted diet and prescribed protein substitutes as part of their usual clinical care. They are not receiving sapropterin or sepiapterin. Dietary treatment is not assigned or modified by this observational study.

DRUG

Sapropterin Dihydrochloride

Participants receive sapropterin as part of their usual clinical care, alongside an individualised phenylalanine-restricted diet. Sapropterin treatment and dosage are prescribed independently of this observational study and are not assigned or modified by the investigators.

DRUG

Sepiapterin

Participants receive sepiapterin as part of their existing clinical management, alongside an individualised phenylalanine-restricted diet. Sepiapterin treatment and dosage are determined independently of this observational study and are not assigned or modified by the investigators.

Sponsors & Collaborators

• Universidade Nova de Lisboa

  collaborator OTHER

• Birmingham Women's and Children's NHS Foundation Trust

  lead OTHER

Principal Investigators

• Anita MacDonald, PhD · Birmingham Children's Hospital

Eligibility

Min Age

3 Years

Max Age

17 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-10-01

Primary Completion

2026-12-31

Completion

2026-12-31

Countries

• United Kingdom

Study Locations