JIMD Reports, Volume 36

van Dam, Esther, Daly, Anne, Venema-Liefaard, Gineke, van Rijn, Margreet, Derks, Terry G. J., McKiernan, Patrick J., Rebecca Heiner-Fokkema, M., MacDonald, Anita, van Spronsen, Francjan J., Derks, Terry G J, McKiernan, Patrick J, Rebecca Heiner-Fokkema, M, van Spronsen, Francjan J, Esther van Dam, 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

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