Tyrosinemia type 1 (TT1) treatment with 2-(2-nitro-4-trifluormethyl-benzyl)-1,3-cyclohexanedione (NTBC) and a
phenylalanine-
tyrosine restricted diet is associated with low
phenylalanine concentrations.
Phenylalanine supplementation is prescribed without comprehensive consideration about its effect on metabolic control. We investigated the effect of
phenylalanine supplementation on bloodspot
phenylalanine,
tyrosine, NTBC and
succinylacetone. Eleven TT1 patients received 0, 20 and 40 mg/kg/day
phenylalanine supplementation with the
phenylalanine-
tyrosine free L-
amino acid supplements. Bloodspots were collected before breakfast, midday and evening meal. Differences between study periods, sample times and days within a study period were studied using (generalized) linear mixed model analyses. Twenty and 40 mg/kg/day
phenylalanine supplementation prevented daytime
phenylalanine decreases (p = 0.05) and most low
phenylalanine concentrations, while
tyrosine concentrations increased (p < 0.001). Furthermore, NTBC and
succinylacetone concentrations did not differ between study periods. To conclude, 20 mg/kg/day
phenylalanine supplementation can prevent most low
phenylalanine concentrations without increasing
tyrosine to concentrations above the target range or influencing NTBC and
succinylacetone concentrations, while 40 mg/kg/day increased
tyrosine concentrations to values above the targeted range. Additionally, this study showed that the effect of
phenylalanine supplementation, and a possible
phenylalanine deficiency, should be assessed using pre-midday meal blood samples that could be combined with an overnight fasted sample when in doubt.