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. 2021 Aug 19;10(16):3674.
doi: 10.3390/jcm10163674.

Urine Phenylacetylglutamine Determination in Patients with Hyperphenylalaninemia

Fernando Andrade  1 , Ainara Cano  2 , María Unceta Suarez  2   3 , Arantza Arza  2   3 , Ana Vinuesa  4 , Leticia Ceberio  2 , Nuria López-Oslé  2 , Gorka de Frutos  2 , Raquel López-Oceja  1 , Elena Aznal  5 , Domingo González-Lamuño  6 , Javier de Las Heras  2   4   7
Affiliations

Urine Phenylacetylglutamine Determination in Patients with Hyperphenylalaninemia

Fernando Andrade et al. J Clin Med. .

Abstract

Phenylketonuria (PKU), an autosomal-recessive inborn error of phenylalanine (Phe) metabolism is the most prevalent disorder of amino acid metabolism. Currently, clinical follow-up relies on frequent monitoring of Phe levels in blood. We hypothesize that the urine level of phenylacetylglutamine (PAG), a phenyl-group marker, could be used as a non-invasive biomarker. In this cross-sectional study, a validated liquid chromatography coupled to tandem mass spectrometry (LC-MS) method was used for urinary PAG quantification in 35 participants with hyperphenylalaninemia (HPA) and 33 age- and sex-matched healthy controls. We have found that (a) PKU patients present higher urine PAG levels than healthy control subjects, and that (b) there is a significant correlation between urine PAG and circulating Phe levels in patients with HPA. In addition, we show a significant strong correlation between Phe levels from venous blood samples and from capillary finger-prick dried blood spot (DBS) samples collected at the same time in patients with HPA. Further research in order to assess the potential role of urine PAG as a non-invasive biomarker in PKU is warranted.

Keywords: biomarkers; dried blood spot; phenylacetylglutamine; phenylalanine; phenylalanine hydroxylase deficiency; phenylketonuria.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Phenylacetylglutamine concentration in urine from patients with mHPA/PKU (n = 35) and their healthy controls (n = 33). Mild hyperphenylalaninemia (mHPA), phenylketonuria (PKU), phenylacetylglutamine (PAG), creatinine (Cr).
Figure 2
Figure 2
Correlations between urine PAG/Cr and (A) mean of the last year DBS Phe levels, (B) DBS Phe levels the day of the visit, and (C) plasma Phe levels the day of the visit (C). Phenylacetylglutamine (PAG), creatinine (Cr), dried blood spot (DBS), phenylalanine (Phe).
Figure 2
Figure 2
Correlations between urine PAG/Cr and (A) mean of the last year DBS Phe levels, (B) DBS Phe levels the day of the visit, and (C) plasma Phe levels the day of the visit (C). Phenylacetylglutamine (PAG), creatinine (Cr), dried blood spot (DBS), phenylalanine (Phe).
Figure 3
Figure 3
Correlation between the concentration of phenylalanine in plasma and in DBS in mHPA/PKU patients. Mild hyperphenylalaninemia (mHPA), phenylketonuria (PKU), dried blood spot (DBS), phenylalanine (Phe).
See this image and copyright information in PMC

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