Preliminary Investigation of Microbiome and Dietary Differences in Patients with Phenylketonuria on Enzyme Substitution Therapy Compared to Traditional Therapies

BackgroundPhenylketonuria (PKU) is an inborn error of metabolism that impairs the function of the enzyme phenylalanine hydroxylase. Historical treatment includes limiting dietary phenylalanine (Phe) consumption while supplementing with medical food; however, this treatment has been associated with complications, such as nutritional deficiencies and disruptions in the gut microbiota.ObjectiveThe study aim was to compare dietary and gut microbiome differences between adult patients on a traditional PKU diet with those receiving the enzyme substitution therapy Palynziq on a liberalized diet while controlling blood Phe levels to <600 μmol/L (to convert to mg/dL divide by 60.5).DesignA cross-sectional study was conducted comparing patients on a traditional Phe-restricted diet with patients receiving Palynziq eating a liberalized diet.Participants/settingSix patients eating a traditional Phe-restricted diet with medical food and 6 patients on Palynziq eating a liberalized diet without medical food intake for more than 3 years were selected from the University of Kentucky Metabolic Clinic from August to December 2019.Main outcome measuresNutrient intake from 3-day diet records and fecal microbiome taxonomic abundances were analyzed.Statistical analysisMann-Whitney U tests were used for dietary data analysis. Differential abundance analysis for microbiome taxa and pathway data was done using DESeq2 analysis.ResultsDietary data showed patients receiving Palynziq consumed a lower percent of kilocalories from total protein and lower amounts of most micronutrients, but consumed greater amounts of intact protein and cholesterol (P < .05). Microbiome data revealed a greater abundance of the phylum Verrucomicrobia and genus Lachnobacterium in the Traditional group and a greater abundance of the genus Prevotella in the Palynziq group (P < .05). Pathway analysis depicted greater enrichment in carotenoid and amino acid metabolism pathways in the Traditional group (P < .05). Protein (% kcal), dietary fiber (g), fat (% kcal), linolenic acid (% Dietary Reference Intakes), and age were correlated with the underlying microbial community structure for both groups combined.ConclusionsPatients with PKU treated with Palynziq on a liberalized diet manifest significant differences in diet composition compared with those treated with traditional Phe-restricted diets. Several of these dietary differences may affect the microbiome architecture.     

Pegvaliase: a novel treatment option for adults with phenylketonuria

Objective: In May 2018, the US Food and Drug Administration approved pegvaliase-pqpz (Palynziq*), the first enzyme substitution therapy for the treatment of phenylketonuria (PKU). This article provides an overview of the mechanism of action, pharmacokinetic properties, clinical efficacy, and the safety and tolerability profile of pegvaliase.

Methods: Relevant information was identified through a comprehensive literature search of several databases using the keywords pegvaliase, rAvPAL-PEG, and phenylketonuria. Additional information was gathered from the pegvaliase package insert, posters presented at scientific meetings, and materials provided from the manufacturer, BioMarin.

Results: Pegvaliase is effective in decreasing blood phenylalanine levels, and is associated with a manageable side-effect profile. Phase III clinical trial data demonstrated that 60.7% of patients were able to achieve blood phenylalanine levels less than the guideline recommended 360 µmol/L at 24 months. Brief sub-studies also showed the improvement in inattention symptoms in patients treated with pegvaliase, compared to placebo.

Conclusion: Pegvaliase is a promising new treatment option for adults living with PKU. Further studies are warranted to determine long-term safety and clinical efficacy in sub-populations.