Diurnal variation of phenylalanine concentrations in tyrosinaemia type 1: should we be concerned?

Tyrosinaemia type 1 (HT1) is treated with a tyrosine and phenylalanine-restricted diet, amino acids free of phenylalanine and tyrosine, and nitisinone (NTBC). Treatment guidelines recommend plasma tyrosine between 200-400 μm and phenylalanine at least >30 μm. There is little information on the diurnal variation of plasma tyrosine or phenylalanine in HT1. Low plasma phenylalanine <30 μm may be associated with poor growth and cognitive delay. The present study aimed to document diurnal variation of tyrosine and phenylalanine plasma concentrations and growth in children with HT1.

Median tyrosine and phenylalanine plasma concentrations were reviewed retrospectively over 3 years in 11 subjects (median age 4 years) with HT1. Subjects routinely collected morning fasting blood samples but afternoon nonfasted samples were taken in the clinic (<10% of samples). Growth Z-scores were calculated.

The percentage of all plasma phenylalanine concentrations <30 μm was 8.6% and <40 μm was 13.6%. Only 2% of fasting morning phenylalanine concentrations were <30 μm, compared to 83% of nonfasting afternoon samples. All but one child had a height Z-score <0.

Blood phenylalanine concentrations were consistently lower in the afternoon. Taking blood samples at variable time points in the day may lead to variation in interpreting dietary control. A detailed study is necessary to examine the 24-h diurnal variation of plasma phenylalanine and tyrosine in HT1. It is possible that phenylalanine concentrations may be very low for a substantive time over 24 h and the potential impact that this may have on cognitive development and growth in children is unknown.