Background and objective: Neonatal screening and early treatment have changed the natural history of PKU, preventing severe neurological and intellectual disability. Nevertheless, the outcome of the disease in earlytreated adult patients (ETPKU) is less than optimal, the predictive value of metabolic biomarkers is feeble, and the recommended levels of blood phenylalanine (Phe) for adulthood are controversial. A crucial question whose answer will improve our understanding and treatment of PKU is whether cognitive outcomes can be modulated by levels of Phe even in early-treated adults. To address this question, we carried out an interventional study in seven ETPKU women planning a pregnancy. Methods: They underwent an extensive neurocognitive assessment at baseline, and 3 and 6 months after having attained the blood Phe concentration recommended to prevent PKU fetopathy, but before pregnancy. Results: After 3 and 6 months with a stable blood Phe level of about 240 & mu;mol/L, all participants experienced significant improvements in almost all neurocognitive domains and tasks. IQ also increased of 11 to 21 points from the last assessment before enrolment. This pattern remained strong and consistent after correction for multiple comparisons. Conclusion: Our results indicate that a) strong cognitive improvement is possible even in adulthood and may be demonstrated by lowering Phe near normal levels; b) testing cognition under different metabolic conditions may unveil an individual vulnerability to Phe. These results pave the way for personalised treatment of the disease in adults with ETPKU.
Towards precision medicine for phenylketonuria: The effect of restoring a strict metabolic control in adult patients with early-treated phenylketonuria / Manti, Filippo; Nardecchia, Francesca; De Leo, Sabrina; Carducci, Claudia; Romani, Cristina; Palermo, Liana; Angeloni, Antonio; Leuzzi, Vincenzo. - In: MOLECULAR GENETICS AND METABOLISM. - ISSN 1096-7192. - 140:3(2023), p. 107666. [10.1016/j.ymgme.2023.107666]
Towards precision medicine for phenylketonuria: The effect of restoring a strict metabolic control in adult patients with early-treated phenylketonuria
Manti, FilippoPrimo
Writing – Original Draft Preparation
;Nardecchia, FrancescaWriting – Original Draft Preparation
;De Leo, SabrinaData Curation
;Romani, CristinaWriting – Review & Editing
;Palermo, LianaWriting – Review & Editing
;Angeloni, AntonioWriting – Review & Editing
;Leuzzi, Vincenzo
Ultimo
Writing – Original Draft Preparation
2023
Abstract
Background and objective: Neonatal screening and early treatment have changed the natural history of PKU, preventing severe neurological and intellectual disability. Nevertheless, the outcome of the disease in earlytreated adult patients (ETPKU) is less than optimal, the predictive value of metabolic biomarkers is feeble, and the recommended levels of blood phenylalanine (Phe) for adulthood are controversial. A crucial question whose answer will improve our understanding and treatment of PKU is whether cognitive outcomes can be modulated by levels of Phe even in early-treated adults. To address this question, we carried out an interventional study in seven ETPKU women planning a pregnancy. Methods: They underwent an extensive neurocognitive assessment at baseline, and 3 and 6 months after having attained the blood Phe concentration recommended to prevent PKU fetopathy, but before pregnancy. Results: After 3 and 6 months with a stable blood Phe level of about 240 & mu;mol/L, all participants experienced significant improvements in almost all neurocognitive domains and tasks. IQ also increased of 11 to 21 points from the last assessment before enrolment. This pattern remained strong and consistent after correction for multiple comparisons. Conclusion: Our results indicate that a) strong cognitive improvement is possible even in adulthood and may be demonstrated by lowering Phe near normal levels; b) testing cognition under different metabolic conditions may unveil an individual vulnerability to Phe. These results pave the way for personalised treatment of the disease in adults with ETPKU.File | Dimensione | Formato | |
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