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Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
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Pre-analytic decrease of phenylalanine in plasma of patients with phenylketonuria treated with pegvaliase.

Coleman Turgeon1, Kari Casas2, Ryan Flanagan1

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Phenylketonuria (PKU) patients treated with pegvaliase may experience inaccurate blood phenylalanine (Phe) levels due to ongoing enzyme activity post-collection. Prompt sample preparation is crucial to prevent Phe degradation and ensure reliable monitoring for neurological health.

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Area of Science:

  • Biochemistry
  • Clinical Chemistry
  • Pharmacology

Background:

  • Phenylketonuria (PKU) management traditionally involves a phenylalanine (Phe)-restricted diet.
  • Pegvaliase, an enzyme therapy, offers an alternative treatment for adults with PKU by metabolizing excess Phe.
  • Accurate blood Phe monitoring is essential for managing PKU and preventing neurological complications.

Purpose of the Study:

  • Investigate discrepant phenylalanine (Phe) measurements in a PKU patient treated with pegvaliase.
  • Determine if residual pegvaliase activity in collected specimens affects Phe levels.
  • Identify pre-analytical factors influencing Phe measurement accuracy in patients on pegvaliase therapy.

Main Methods:

  • Performed spiking studies to assess Phe degradation over time at ambient temperatures.
  • Evaluated the effect of protein crash sample preparation on pegvaliase activity.
  • Analyzed discrepant Phe results from patient specimens.

Main Results:

  • Pegvaliase activity continued to degrade Phe in collected specimens at ambient temperatures.
  • Protein crash sample preparation effectively deactivated residual pegvaliase.
  • Discrepant Phe results were attributed to post-collection Phe degradation.

Conclusions:

  • Residual pegvaliase activity can lead to inaccurate Phe measurements in PKU patients.
  • Immediate deactivation of pegvaliase post-collection is necessary.
  • Consider stringent pre-analytical requirements, alternative matrices (e.g., dried blood spots), or point-of-care testing for reliable Phe monitoring.