The neurological and neuropsychiatric spectrum of adults with late-treated phenylketonuria
(2021) In Parkinsonism and Related Disorders 89. p.167-175- Abstract
Introduction: Phenylketonuria (PKU) is a rare, treatable inborn error of metabolism with frequent neurological and neuropsychiatric complications, especially in undiagnosed or insufficiently treated individuals. Given the wide range of clinical presentations and the importance of treatment implications, we here delineate the neurological and neuropsychiatric symptom spectrum in a large cohort of previously unreported adults with late-treated PKU. Methods: We consecutively evaluated late-treated PKU cases and pooled clinical and paraclinical data, including video-material, from three centers with expertise in complex movement disorders, inborn errors of metabolism and pediatrics. Results: 26 individuals were included (10 females, median... (More)
Introduction: Phenylketonuria (PKU) is a rare, treatable inborn error of metabolism with frequent neurological and neuropsychiatric complications, especially in undiagnosed or insufficiently treated individuals. Given the wide range of clinical presentations and the importance of treatment implications, we here delineate the neurological and neuropsychiatric symptom spectrum in a large cohort of previously unreported adults with late-treated PKU. Methods: We consecutively evaluated late-treated PKU cases and pooled clinical and paraclinical data, including video-material, from three centers with expertise in complex movement disorders, inborn errors of metabolism and pediatrics. Results: 26 individuals were included (10 females, median age 52 years). Developmental delay and intellectual disability were omnipresent with severe impairment of expressive communication noted in 50% of cases. Movement disorders were prevalent (77%), including tremor (38%, mostly postural), stereotypies (38%), and tics (19%). One case had neurodegenerative levodopa-responsive parkinsonism. Mild ataxia was noted in 54% of cases and 31% had a history of seizures. Neuropsychiatric characteristics included obsessive-compulsive (35%) and self-injurious behaviors (31%), anxiety (27%), depression (19%) and features compatible with those observed in individuals with autism spectrum disorder (19%). Neuroimaging revealed mild white matter changes. Adherence to dietary treatment was inconsistent in the majority of cases, particularly throughout adolescence. Conclusion: A history of movement disorders, particularly tremor, stereotypies and tics, in the presence of developmental delay, intellectual disability and neuropsychiatric features, such as obsessive-compulsive and self-injurious behaviors in adults should prompt the diagnostic consideration of PKU. Initiation and adherence to (dietary) treatment can ameliorate the severity of these symptoms.
(Less)
- author
- organization
- publishing date
- 2021-08
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Metabolic disorder, Movement disorders, Neurology, Neuropsychiatry, Phenylketonuria
- in
- Parkinsonism and Related Disorders
- volume
- 89
- pages
- 167 - 175
- publisher
- Elsevier
- external identifiers
-
- scopus:85112141654
- pmid:34391119
- ISSN
- 1353-8020
- DOI
- 10.1016/j.parkreldis.2021.06.011
- language
- English
- LU publication?
- yes
- additional info
- Funding Information: This research project was supported by a grant from the VolkswagenStiftung (Freigeist, AZ 94268 ) held by CG. TM is a participant in the BIH-Charité Clinician Scientist Program funded by the Charité-Universitätsmedizin Berlin and the Berlin Institute of Health . The project was also supported by the Slovak Grant and Development Agency ( APVV-18-0547 ) and IBM Faculty Award ( UR 09/2019 ) grants to MS. Funding Information: PF has received a research grant from Vitaflow, Germany, outside the submitted work. Funding Information: MS is a consultant for Abbvie and Biogen, received speakers honoraria from Abbvie, Boston Scientific, Desitin, Ever pharma, Krka, Medtronic, Sandoz, UCB and the International Parkinson and Movement Disorder Society, all outside this submitted work; he holds grants from the Slovak Grant and Development Agency (APVV-18-0547), the Slovak Research and Grant Agency (VEGA 1/0596/19) and IBM (UR 09/2019). Publisher Copyright: © 2021 Elsevier Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
- id
- 274b28f5-d7df-43bb-b851-d258baec5526
- date added to LUP
- 2021-08-23 10:23:08
- date last changed
- 2024-04-06 07:24:16
@article{274b28f5-d7df-43bb-b851-d258baec5526,
abstract = {{<p>Introduction: Phenylketonuria (PKU) is a rare, treatable inborn error of metabolism with frequent neurological and neuropsychiatric complications, especially in undiagnosed or insufficiently treated individuals. Given the wide range of clinical presentations and the importance of treatment implications, we here delineate the neurological and neuropsychiatric symptom spectrum in a large cohort of previously unreported adults with late-treated PKU. Methods: We consecutively evaluated late-treated PKU cases and pooled clinical and paraclinical data, including video-material, from three centers with expertise in complex movement disorders, inborn errors of metabolism and pediatrics. Results: 26 individuals were included (10 females, median age 52 years). Developmental delay and intellectual disability were omnipresent with severe impairment of expressive communication noted in 50% of cases. Movement disorders were prevalent (77%), including tremor (38%, mostly postural), stereotypies (38%), and tics (19%). One case had neurodegenerative levodopa-responsive parkinsonism. Mild ataxia was noted in 54% of cases and 31% had a history of seizures. Neuropsychiatric characteristics included obsessive-compulsive (35%) and self-injurious behaviors (31%), anxiety (27%), depression (19%) and features compatible with those observed in individuals with autism spectrum disorder (19%). Neuroimaging revealed mild white matter changes. Adherence to dietary treatment was inconsistent in the majority of cases, particularly throughout adolescence. Conclusion: A history of movement disorders, particularly tremor, stereotypies and tics, in the presence of developmental delay, intellectual disability and neuropsychiatric features, such as obsessive-compulsive and self-injurious behaviors in adults should prompt the diagnostic consideration of PKU. Initiation and adherence to (dietary) treatment can ameliorate the severity of these symptoms.</p>}},
author = {{Mainka, Tina and Fischer, Jan Frederik and Huebl, Julius and Jung, Alexandra and Lier, Dinah and Mosejova, Alexandra and Skorvanek, Matej and de Koning, Tom J. and Kühn, Andrea A. and Freisinger, Peter and Ziagaki, Athanasia and Ganos, Christos}},
issn = {{1353-8020}},
keywords = {{Metabolic disorder; Movement disorders; Neurology; Neuropsychiatry; Phenylketonuria}},
language = {{eng}},
pages = {{167--175}},
publisher = {{Elsevier}},
series = {{Parkinsonism and Related Disorders}},
title = {{The neurological and neuropsychiatric spectrum of adults with late-treated phenylketonuria}},
url = {{http://dx.doi.org/10.1016/j.parkreldis.2021.06.011}},
doi = {{10.1016/j.parkreldis.2021.06.011}},
volume = {{89}},
year = {{2021}},
}