Do early‐treated adults with phenylketonuria sense high phenylalanine levels?

Abstract This study aimed to analyze whether early‐treated adults with phenylketonuria (PKU) can subjectively sense high phenylalanine (Phe) concentrations and whether a possible impact of Phe on objective measures of cognitive performance and mood reflects patients' self‐perception. Data from the PICO study, a randomized, placebo‐controlled, double‐blind, crossover trial, were analyzed. Twenty‐eight adults with PKU received either Phe capsules or placebo in two 4‐week intervention periods in a randomized order, with a 4‐week washout in between. The median Phe level increased from 852 μmol/L (interquartile range: 345) to 1455 μmol/L (interquartile range: 369). Neuropsychological assessments were performed at four study visits. At the end of the last study visit, patients were asked whether they could discern the Phe intervention period. Seven of 28 (25%) patients stated that they could not discern between the Phe and the placebo period. Twenty‐one of 28 (75%) patients subjectively thought to sense high Phe levels. Of the 21 patients, 12 (57%) correctly identified the Phe period, whereas 9 (43%) received placebo at the time when they thought they would receive the high Phe load. Binomial tests showed that the probability of 12 out of 21 is p = 0.140, and 12 out of 28 is p = 0.113. The “Right‐Guess” group showed significantly higher Phe changes than the “Wrong‐Guess” group. Cognitive performance and standardized mood assessment did not significantly differ, and both groups reported similar subjective negative impact on cognition and mood. In conclusion, adults with early‐treated PKU cannot effectively identify high Phe levels, although some individuals may be able to perceive more pronounced increases in Phe levels.