Publication

Predictability and inconsistencies of cognitive outcome in patients with phenylketonuria and personalised therapy: The challenge for the future guidelines

Leuzzi, V., Chiarotti, F., Nardecchia, F., van Vliet, D. & van Spronsen, F. J., Feb-2020, In : JOURNAL OF MEDICAL GENETICS. 57, 2, p. 145-150 6 p.

Research output: Contribution to journalReview articleAcademicpeer-review

APA

Leuzzi, V., Chiarotti, F., Nardecchia, F., van Vliet, D., & van Spronsen, F. J. (2020). Predictability and inconsistencies of cognitive outcome in patients with phenylketonuria and personalised therapy: The challenge for the future guidelines. JOURNAL OF MEDICAL GENETICS, 57(2), 145-150. https://doi.org/10.1136/jmedgenet-2019-106278

Author

Leuzzi, Vincenzo ; Chiarotti, Flavia ; Nardecchia, Francesca ; van Vliet, Danique ; van Spronsen, Francjan J. / Predictability and inconsistencies of cognitive outcome in patients with phenylketonuria and personalised therapy : The challenge for the future guidelines. In: JOURNAL OF MEDICAL GENETICS. 2020 ; Vol. 57, No. 2. pp. 145-150.

Harvard

Leuzzi, V, Chiarotti, F, Nardecchia, F, van Vliet, D & van Spronsen, FJ 2020, 'Predictability and inconsistencies of cognitive outcome in patients with phenylketonuria and personalised therapy: The challenge for the future guidelines', JOURNAL OF MEDICAL GENETICS, vol. 57, no. 2, pp. 145-150. https://doi.org/10.1136/jmedgenet-2019-106278

Standard

Predictability and inconsistencies of cognitive outcome in patients with phenylketonuria and personalised therapy : The challenge for the future guidelines. / Leuzzi, Vincenzo; Chiarotti, Flavia; Nardecchia, Francesca; van Vliet, Danique; van Spronsen, Francjan J.

In: JOURNAL OF MEDICAL GENETICS, Vol. 57, No. 2, 02.2020, p. 145-150.

Research output: Contribution to journalReview articleAcademicpeer-review

Vancouver

Leuzzi V, Chiarotti F, Nardecchia F, van Vliet D, van Spronsen FJ. Predictability and inconsistencies of cognitive outcome in patients with phenylketonuria and personalised therapy: The challenge for the future guidelines. JOURNAL OF MEDICAL GENETICS. 2020 Feb;57(2):145-150. https://doi.org/10.1136/jmedgenet-2019-106278


BibTeX

@article{e187f71df752439eb4a05735e2fe5a46,
title = "Predictability and inconsistencies of cognitive outcome in patients with phenylketonuria and personalised therapy: The challenge for the future guidelines",
abstract = "Phenylketonuria (PKU) is a prototypical model of a neurodevelopmental metabolic disease that follows a cascade of pathological events affecting brain maturation and functioning. Neonatal screening and early treatment have eradicated the classical PKU phenotype in patients with early and continuously treated phenylketonuria (ECTPKU). However, effort is required to optimise the treatment of the disease to minimise the risk of lifelong neurological, cognitive and behavioural impairment, and to solve issues on the variability in clinical outcome that are rather not understood and has yet hampered a more personalised approach to its treatment. The aim of the present review is to focus on the inconsistencies in the clinical outcome of adult patients with ECTPKU unexplained by the biochemical markers adopted for the monitoring of the disease to date. The interindividual variability of clinical outcome in late as well as in early treated patients under similar biochemical control suggests the existence of disease-independent determinants influencing the individual vulnerability to the neurotoxic effect of phenylalanine. This is further supported by the low predictive power of blood phenylalanine on the clinical outcome from the second decade of life onwards. In conclusion, individual vulnerability to the metabolic alterations of PKU contributes to the prognosis of PKU, also in patients with ECTPKU. The biological factors constitutive of this vulnerability are unknown (but have not been the object of many studies so far) and should be the target of further research as prerequisite for a personalised treatment aimed at avoiding burden and costs of overtreatment and clinical consequences and risks of undertreatment in patients with PKU.",
keywords = "EARLY-TREATED PHENYLKETONURIA, YOUNG-ADULTS, PKU-PATIENTS, PHENYLALANINE, INTELLIGENCE, METAANALYSIS, ADOLESCENTS, IMPAIRMENT, DEFICIENCY, SYMPTOMS",
author = "Vincenzo Leuzzi and Flavia Chiarotti and Francesca Nardecchia and {van Vliet}, Danique and {van Spronsen}, {Francjan J.}",
year = "2020",
month = feb,
doi = "10.1136/jmedgenet-2019-106278",
language = "English",
volume = "57",
pages = "145--150",
journal = "JOURNAL OF MEDICAL GENETICS",
issn = "0022-2593",
publisher = "BMJ PUBLISHING GROUP",
number = "2",

}

RIS

TY - JOUR

T1 - Predictability and inconsistencies of cognitive outcome in patients with phenylketonuria and personalised therapy

T2 - The challenge for the future guidelines

AU - Leuzzi, Vincenzo

AU - Chiarotti, Flavia

AU - Nardecchia, Francesca

AU - van Vliet, Danique

AU - van Spronsen, Francjan J.

PY - 2020/2

Y1 - 2020/2

N2 - Phenylketonuria (PKU) is a prototypical model of a neurodevelopmental metabolic disease that follows a cascade of pathological events affecting brain maturation and functioning. Neonatal screening and early treatment have eradicated the classical PKU phenotype in patients with early and continuously treated phenylketonuria (ECTPKU). However, effort is required to optimise the treatment of the disease to minimise the risk of lifelong neurological, cognitive and behavioural impairment, and to solve issues on the variability in clinical outcome that are rather not understood and has yet hampered a more personalised approach to its treatment. The aim of the present review is to focus on the inconsistencies in the clinical outcome of adult patients with ECTPKU unexplained by the biochemical markers adopted for the monitoring of the disease to date. The interindividual variability of clinical outcome in late as well as in early treated patients under similar biochemical control suggests the existence of disease-independent determinants influencing the individual vulnerability to the neurotoxic effect of phenylalanine. This is further supported by the low predictive power of blood phenylalanine on the clinical outcome from the second decade of life onwards. In conclusion, individual vulnerability to the metabolic alterations of PKU contributes to the prognosis of PKU, also in patients with ECTPKU. The biological factors constitutive of this vulnerability are unknown (but have not been the object of many studies so far) and should be the target of further research as prerequisite for a personalised treatment aimed at avoiding burden and costs of overtreatment and clinical consequences and risks of undertreatment in patients with PKU.

AB - Phenylketonuria (PKU) is a prototypical model of a neurodevelopmental metabolic disease that follows a cascade of pathological events affecting brain maturation and functioning. Neonatal screening and early treatment have eradicated the classical PKU phenotype in patients with early and continuously treated phenylketonuria (ECTPKU). However, effort is required to optimise the treatment of the disease to minimise the risk of lifelong neurological, cognitive and behavioural impairment, and to solve issues on the variability in clinical outcome that are rather not understood and has yet hampered a more personalised approach to its treatment. The aim of the present review is to focus on the inconsistencies in the clinical outcome of adult patients with ECTPKU unexplained by the biochemical markers adopted for the monitoring of the disease to date. The interindividual variability of clinical outcome in late as well as in early treated patients under similar biochemical control suggests the existence of disease-independent determinants influencing the individual vulnerability to the neurotoxic effect of phenylalanine. This is further supported by the low predictive power of blood phenylalanine on the clinical outcome from the second decade of life onwards. In conclusion, individual vulnerability to the metabolic alterations of PKU contributes to the prognosis of PKU, also in patients with ECTPKU. The biological factors constitutive of this vulnerability are unknown (but have not been the object of many studies so far) and should be the target of further research as prerequisite for a personalised treatment aimed at avoiding burden and costs of overtreatment and clinical consequences and risks of undertreatment in patients with PKU.

KW - EARLY-TREATED PHENYLKETONURIA

KW - YOUNG-ADULTS

KW - PKU-PATIENTS

KW - PHENYLALANINE

KW - INTELLIGENCE

KW - METAANALYSIS

KW - ADOLESCENTS

KW - IMPAIRMENT

KW - DEFICIENCY

KW - SYMPTOMS

U2 - 10.1136/jmedgenet-2019-106278

DO - 10.1136/jmedgenet-2019-106278

M3 - Review article

C2 - 31484718

VL - 57

SP - 145

EP - 150

JO - JOURNAL OF MEDICAL GENETICS

JF - JOURNAL OF MEDICAL GENETICS

SN - 0022-2593

IS - 2

ER -

ID: 129252547