There are no established criteria for the identification of patients with phenylketonuria who are long-term BH4 responsive. Hennermann et al. reported that, based on their cohort of patients, long-term BH4 responsiveness may be predicted already during neonatal period by determining maximum pretreatment phenylalanine and phenylalanine/tyrosine concentrations, neonatal BH4 loading and PAH genotype. The most predictive value for long-term BH4 responsiveness was the combination of pretreatment phenylalanine of < 1200 ?mol/L, pretreatment phenylalanine/tyrosine ratio of <15, phenylalanine/tyrosine ratio of <15 on treatment, phenylalanine tolerance of >20mg/kg/day at age 3 years, positive neonatal BH4 loading, and at least one putative BH4 responsive mutation (p = 0.00024). Hennermann et al. concluded that a clear defined protocol is necessary to identify patients for long-term BH4 treatment.
Long-term treatment with tetrahydrobiopterin in phenylketonuria: treatment strategies and prediction of long-term responders. Hennermann et al. Mol Genet Metab. 2012 Nov;107(3):294-301. PMID: 23062575
posted by Yannis Trakadis, MD