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@ARTICLE{Pilotto:140655,
author = {Pilotto, Andrea and Blau, Nenad and Leks, Edytha and
Schulte, Claudia and Deuschle, Christian and Zipser, Carl
and Piel, David and Freisinger, Peter and Gramer, Gwendolyn
and Kölker, Stefan and Haas, Dorothea and Burgard, Peter
and Nawroth, Peter and Georg, Hoffmann and Scheffler, Klaus
and Berg, Daniela and Trefz, Friedrich},
title = {{C}erebrospinal fluid biogenic amines depletion and brain
atrophy in adult patients with phenylketonuria.},
journal = {Journal of inherited metabolic disease},
volume = {42},
number = {3},
issn = {0141-8955},
address = {Dordrecht [u.a.]},
publisher = {Springer Science + Business Media B.V},
reportid = {DZNE-2020-06977},
pages = {398-406},
year = {2019},
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 / Biogenic Amines:
cerebrospinal fluid / Case-Control Studies / Female / Gray
Matter: pathology / Homovanillic Acid: blood / Homovanillic
Acid: cerebrospinal fluid / Humans / Linear Models /
Magnetic Resonance Imaging / Male / Middle Aged /
Phenylketonurias: blood / Phenylketonurias: cerebrospinal
fluid},
cin = {AG Berg / AG Gasser},
ddc = {610},
cid = {I:(DE-2719)5000055 / I:(DE-2719)1210000},
pnm = {345 - Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30706953},
doi = {10.1002/jimd.12049},
url = {https://pub.dzne.de/record/140655},
}