title: What Is the Best Blood Sampling Time for Metabolic Control of Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients?
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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dietetics, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands. e.van.dam@umcg.nl.
authors.forename: Esther
authors.initials: E
authors.lastname: van Dam
authors.affiliation: Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Daly
authors.affiliation: Department of Dietetics, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands.
authors.forename: Gineke
authors.initials: G
authors.lastname: Venema-Liefaard
authors.affiliation: Department of Dietetics, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands.
authors.forename: Margreet
authors.initials: M
authors.lastname: van Rijn
authors.affiliation: Department of Pediatrics, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands.
authors.forename: Terry G J
authors.initials: TGJ
authors.lastname: Derks
authors.affiliation: Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: McKiernan
authors.affiliation: Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Rebecca Heiner-Fokkema
authors.affiliation: Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Anita
authors.initials: A
authors.lastname: MacDonald
authors.affiliation: Department of Pediatrics, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands.
authors.forename: Francjan J
authors.initials: FJ
authors.lastname: van Spronsen