Stress induced hyperphenylalaninemia tied to worse ICU prognosis

The main results of this study were:

1. This study included 497 patients. Elevated phenylalanine concentrations were independently associated with increased mortality risk.

2. Patients with SHP had a higher risk of death compared with those without SHP.

3. SHP was associated with hepatic and renal dysfunction and genetic polymorphisms in the tetrahydrobiopterin (BH4) synthesis (CBR1 and AKR1C3) and recycling (PCBD2) pathways.

4. Higher GRS was associated with lower bioavailability of BH4 in response to stress.

5. Among patients without her SHP at baseline, those with a GRS ≥2 had a higher frequency of developing her SHP during their ICU stay and a higher risk of death compared with those with a GRS <2.

6. Genetic variants did not provide additional prognostic value in patients with SHP at baseline.

In conclusion, in patients without SHP, SHP-associated polymorphisms measured by a GRS of ≥2 were associated with subsequent increased risk of SHP and mortality. Integration of genetic screening, pteridine measurement, and phenylalanine monitoring offers an innovative way to assess critically ill patients, providing key information for precision medicine to improve critical care outcomes.

Reference: 

Wang, C.-H., Chen, W.-S., Liu, M.-H., Lee, C.-Y., Wang, M.-Y., Liang, C.-Y., Chu, C.-M., Wu, H.-P., & Chen, W.-H. (2022). Stress Hyperphenylalaninemia Is Associated With Mortality in Cardiac ICU: Clinical Factors, Genetic Variants, and Pteridines. In Critical Care Medicine: Vol. Publish Ahead of Print. Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1097/ccm.0000000000005640