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Cerebrospinal fluid biogenic amines depletion and brain atrophy in adult patients with phenylketonuria

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Cerebrospinal fluid biogenic amines depletion and brain atrophy in adult patients with phenylketonuria. / Pilotto, Andrea; Blau, Nenad; Leks, Edytha; Schulte, Claudia; Deuschl, Christian; Zipser, Carl; Piel, David; Freisinger, Peter; Gramer, Gwendolyn; Kölker, Stefan; Haas, Dorothea; Burgard, Peter; Nawroth, Peter; Georg, Hoffmann; Scheffler, Klaus; Berg, Daniela; Trefz, Friedrich.

In: J INHERIT METAB DIS, Vol. 42, No. 3, 05.2019, p. 398-406.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Pilotto, A, Blau, N, Leks, E, Schulte, C, Deuschl, C, Zipser, C, Piel, D, Freisinger, P, Gramer, G, Kölker, S, Haas, D, Burgard, P, Nawroth, P, Georg, H, Scheffler, K, Berg, D & Trefz, F 2019, 'Cerebrospinal fluid biogenic amines depletion and brain atrophy in adult patients with phenylketonuria', J INHERIT METAB DIS, vol. 42, no. 3, pp. 398-406. https://doi.org/10.1002/jimd.12049

APA

Pilotto, A., Blau, N., Leks, E., Schulte, C., Deuschl, C., Zipser, C., Piel, D., Freisinger, P., Gramer, G., Kölker, S., Haas, D., Burgard, P., Nawroth, P., Georg, H., Scheffler, K., Berg, D., & Trefz, F. (2019). Cerebrospinal fluid biogenic amines depletion and brain atrophy in adult patients with phenylketonuria. J INHERIT METAB DIS, 42(3), 398-406. https://doi.org/10.1002/jimd.12049

Vancouver

Pilotto A, Blau N, Leks E, Schulte C, Deuschl C, Zipser C et al. Cerebrospinal fluid biogenic amines depletion and brain atrophy in adult patients with phenylketonuria. J INHERIT METAB DIS. 2019 May;42(3):398-406. https://doi.org/10.1002/jimd.12049

Bibtex

@article{f4d573c9df3e4c0b807bc582723893e9,
title = "Cerebrospinal fluid biogenic amines depletion and brain atrophy in adult patients with phenylketonuria",
abstract = "Biogenic amines synthesis in phenylketonuria (PKU) patients with high phenylalanine (Phe) concentration is thought to be impaired due to inhibition of tyrosine and tryptophan hydroxylases and competition with amino acids at the blood-brain barrier. Dopamine and serotonin deficits might explain brain damage and progressive neuropsychiatric impairment in adult PKU patients. Ten early treated adult PKU patients (mean age 38.2 years) and 15 age-matched controls entered the study. Plasma and cerebrospinal fluid (CSF) Phe, 5-hydroxyindoleacetic acid (5-HIAA), 5-hydroxytryptophan (5-HTP), 3,4-dihydroxy-l-phenylalanine (l-DOPA) and homovanillic acid (HVA) were analyzed. Voxel-based morphometry statistical nonparametric mapping was used to test the age-corrected correlation between gray matter atrophy and CSF biogenic amines levels. 5-HIAA and 5-HTP were significantly reduced in PKU patients compared to controls. Significant negative correlations were found between CSF 5-HIAA, HVA, and 5-HTP and Phe levels. A decrease in 5-HIAA and 5-HTP concentrations correlated with precuneus and frontal atrophy, respectively. Lower HVA levels correlated with occipital atrophy. Biogenic amines deficits correlate with specific brain atrophy patterns in adult PKU patients, in line with serotonin and dopamine projections. These findings may support a more rigorous Phe control in adult PKU to prevent neurotransmitter depletion and accelerated brain damage due to aging.",
keywords = "Adult, Atrophy, Biogenic Amines/blood, Case-Control Studies, Female, Gray Matter/pathology, Homovanillic Acid/blood, Humans, Linear Models, Magnetic Resonance Imaging, Male, Middle Aged, Phenylketonurias/blood",
author = "Andrea Pilotto and Nenad Blau and Edytha Leks and Claudia Schulte and Christian Deuschl and Carl Zipser and David Piel and Peter Freisinger and Gwendolyn Gramer and Stefan K{\"o}lker and Dorothea Haas and Peter Burgard and Peter Nawroth and Hoffmann Georg and Klaus Scheffler and Daniela Berg and Friedrich Trefz",
note = "{\textcopyright} 2019 SSIEM.",
year = "2019",
month = may,
doi = "10.1002/jimd.12049",
language = "English",
volume = "42",
pages = "398--406",
journal = "J INHERIT METAB DIS",
issn = "0141-8955",
publisher = "Springer Netherlands",
number = "3",

}

RIS

TY - JOUR

T1 - Cerebrospinal fluid biogenic amines depletion and brain atrophy in adult patients with phenylketonuria

AU - Pilotto, Andrea

AU - Blau, Nenad

AU - Leks, Edytha

AU - Schulte, Claudia

AU - Deuschl, Christian

AU - Zipser, Carl

AU - Piel, David

AU - Freisinger, Peter

AU - Gramer, Gwendolyn

AU - Kölker, Stefan

AU - Haas, Dorothea

AU - Burgard, Peter

AU - Nawroth, Peter

AU - Georg, Hoffmann

AU - Scheffler, Klaus

AU - Berg, Daniela

AU - Trefz, Friedrich

N1 - © 2019 SSIEM.

PY - 2019/5

Y1 - 2019/5

N2 - Biogenic amines synthesis in phenylketonuria (PKU) patients with high phenylalanine (Phe) concentration is thought to be impaired due to inhibition of tyrosine and tryptophan hydroxylases and competition with amino acids at the blood-brain barrier. Dopamine and serotonin deficits might explain brain damage and progressive neuropsychiatric impairment in adult PKU patients. Ten early treated adult PKU patients (mean age 38.2 years) and 15 age-matched controls entered the study. Plasma and cerebrospinal fluid (CSF) Phe, 5-hydroxyindoleacetic acid (5-HIAA), 5-hydroxytryptophan (5-HTP), 3,4-dihydroxy-l-phenylalanine (l-DOPA) and homovanillic acid (HVA) were analyzed. Voxel-based morphometry statistical nonparametric mapping was used to test the age-corrected correlation between gray matter atrophy and CSF biogenic amines levels. 5-HIAA and 5-HTP were significantly reduced in PKU patients compared to controls. Significant negative correlations were found between CSF 5-HIAA, HVA, and 5-HTP and Phe levels. A decrease in 5-HIAA and 5-HTP concentrations correlated with precuneus and frontal atrophy, respectively. Lower HVA levels correlated with occipital atrophy. Biogenic amines deficits correlate with specific brain atrophy patterns in adult PKU patients, in line with serotonin and dopamine projections. These findings may support a more rigorous Phe control in adult PKU to prevent neurotransmitter depletion and accelerated brain damage due to aging.

AB - Biogenic amines synthesis in phenylketonuria (PKU) patients with high phenylalanine (Phe) concentration is thought to be impaired due to inhibition of tyrosine and tryptophan hydroxylases and competition with amino acids at the blood-brain barrier. Dopamine and serotonin deficits might explain brain damage and progressive neuropsychiatric impairment in adult PKU patients. Ten early treated adult PKU patients (mean age 38.2 years) and 15 age-matched controls entered the study. Plasma and cerebrospinal fluid (CSF) Phe, 5-hydroxyindoleacetic acid (5-HIAA), 5-hydroxytryptophan (5-HTP), 3,4-dihydroxy-l-phenylalanine (l-DOPA) and homovanillic acid (HVA) were analyzed. Voxel-based morphometry statistical nonparametric mapping was used to test the age-corrected correlation between gray matter atrophy and CSF biogenic amines levels. 5-HIAA and 5-HTP were significantly reduced in PKU patients compared to controls. Significant negative correlations were found between CSF 5-HIAA, HVA, and 5-HTP and Phe levels. A decrease in 5-HIAA and 5-HTP concentrations correlated with precuneus and frontal atrophy, respectively. Lower HVA levels correlated with occipital atrophy. Biogenic amines deficits correlate with specific brain atrophy patterns in adult PKU patients, in line with serotonin and dopamine projections. These findings may support a more rigorous Phe control in adult PKU to prevent neurotransmitter depletion and accelerated brain damage due to aging.

KW - Adult

KW - Atrophy

KW - Biogenic Amines/blood

KW - Case-Control Studies

KW - Female

KW - Gray Matter/pathology

KW - Homovanillic Acid/blood

KW - Humans

KW - Linear Models

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Phenylketonurias/blood

U2 - 10.1002/jimd.12049

DO - 10.1002/jimd.12049

M3 - SCORING: Journal article

C2 - 30706953

VL - 42

SP - 398

EP - 406

JO - J INHERIT METAB DIS

JF - J INHERIT METAB DIS

SN - 0141-8955

IS - 3

ER -