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What Is the Best Blood Sampling Time for Metabolic Control of Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients?

  • Esther van DamEmail author
  • Anne Daly
  • Gineke Venema-Liefaard
  • Margreet van Rijn
  • Terry G. J. Derks
  • Patrick J. McKiernan
  • M. Rebecca Heiner-Fokkema
  • Anita MacDonald
  • Francjan J. van Spronsen
Research Report
Part of the JIMD Reports book series (JIMD, volume 36)

Abstract

Background: Treatment of hereditary tyrosinemia type 1 with nitisinone and phenylalanine and tyrosine restricted diet has largely improved outcome, but the best blood sampling time for assessment of metabolic control is not known.

Aim: To study diurnal and day-to-day variation of phenylalanine and tyrosine concentrations in tyrosinemia type 1 patients.

Methods: Eighteen tyrosinemia type 1 patients aged >1 year (median age 7.9 years; range 1.6–20.7) were studied. Capillary blood samples were collected 4 times a day (T1: pre-breakfast, T2: pre-midday meal, T3: before evening meal, and T4: bedtime) for 3 days. Linear mixed-effect models were used to investigate diurnal and day-to-day variation of both phenylalanine and tyrosine.

Results: The coefficients of variation of phenylalanine and tyrosine concentrations were the lowest on T1 (13.8% and 14.1%, respectively). Tyrosine concentrations did not significantly differ between the different time points, but phenylalanine concentrations were significantly lower at T2 and T3 compared to T1 (50.1 μmol/L, 29.8 μmol/L, and 37.3 μmol/L, respectively).

Conclusion: Our results indicated that for prevention of too low phenylalanine and too high tyrosine concentrations, measurement of phenylalanine and tyrosine pre-midday meal would be best, since phenylalanine concentrations are the lowest on that time point. Our results also indicated that whilst blood tyrosine concentrations were stable over 24 h, phenylalanine fluctuated. Day-to-day variation was most stable after an overnight fast for both phenylalanine and tyrosine. Therefore, in tyrosinemia type 1 patients the most reliable time point for measuring phenylalanine and tyrosine concentrations to enable interpretation of metabolic control is pre-breakfast.

Notes

Acknowledgement

This study was made possible by a grant of “Stichting Joris” (Dutch Tyrosinemia Foundation).

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Esther van Dam
    • 1
    Email author
  • Anne Daly
    • 2
  • Gineke Venema-Liefaard
    • 1
  • Margreet van Rijn
    • 1
  • Terry G. J. Derks
    • 3
  • Patrick J. McKiernan
    • 2
  • M. Rebecca Heiner-Fokkema
    • 4
  • Anita MacDonald
    • 2
  • Francjan J. van Spronsen
    • 3
  1. 1.Department of DieteticsUniversity of Groningen, University Medical Center Groningen, Beatrix Children’s HospitalGroningenThe Netherlands
  2. 2.Birmingham Children’s HospitalBirminghamUK
  3. 3.Department of PediatricsUniversity of Groningen, University Medical Center Groningen, Beatrix Children’s HospitalGroningenThe Netherlands
  4. 4.Department of Laboratory MedicineUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands

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