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Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, Meta-Analysis and Medical Chart Review

Zellweger spectrum disorder (ZSD) is a rare, debilitating genetic disorder of peroxisome biogenesis that affects multiple organ systems and presents with broad clinical heterogeneity. Although severe, intermediate, and mild forms of ZSD have been described, these designations are often arbitrary, pr...

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Autores principales: Bose, Mousumi, Yergeau, Christine, D’Souza, Yasmin, Cuthbertson, David D., Lopez, Melisa J., Smolen, Alyssa K., Braverman, Nancy E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221082/
https://www.ncbi.nlm.nih.gov/pubmed/35741019
http://dx.doi.org/10.3390/cells11121891
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author Bose, Mousumi
Yergeau, Christine
D’Souza, Yasmin
Cuthbertson, David D.
Lopez, Melisa J.
Smolen, Alyssa K.
Braverman, Nancy E.
author_facet Bose, Mousumi
Yergeau, Christine
D’Souza, Yasmin
Cuthbertson, David D.
Lopez, Melisa J.
Smolen, Alyssa K.
Braverman, Nancy E.
author_sort Bose, Mousumi
collection PubMed
description Zellweger spectrum disorder (ZSD) is a rare, debilitating genetic disorder of peroxisome biogenesis that affects multiple organ systems and presents with broad clinical heterogeneity. Although severe, intermediate, and mild forms of ZSD have been described, these designations are often arbitrary, presenting difficulty in understanding individual prognosis and treatment effectiveness. The purpose of this study is to conduct a scoping review and meta-analysis of existing literature and a medical chart review to determine if characterization of clinical findings can predict severity in ZSD. Our PubMed search for articles describing severity, clinical findings, and survival in ZSD resulted in 107 studies (representing 307 patients) that were included in the review and meta-analysis. We also collected and analyzed these same parameters from medical records of 136 ZSD individuals from our natural history study. Common clinical findings that were significantly different across severity categories included seizures, hypotonia, reduced mobility, feeding difficulties, renal cysts, adrenal insufficiency, hearing and vision loss, and a shortened lifespan. Our primary data analysis also revealed significant differences across severity categories in failure to thrive, gastroesophageal reflux, bone fractures, global developmental delay, verbal communication difficulties, and cardiac abnormalities. Univariable multinomial logistic modeling analysis of clinical findings and very long chain fatty acid (VLCFA) hexacosanoic acid (C26:0) levels showed that the number of clinical findings present among seizures, abnormal EEG, renal cysts, and cardiac abnormalities, as well as plasma C26:0 fatty acid levels could differentiate severity categories. We report the largest characterization of clinical findings in relation to overall disease severity in ZSD. This information will be useful in determining appropriate outcomes for specific subjects in clinical trials for ZSD.
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spelling pubmed-92210822022-06-24 Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, Meta-Analysis and Medical Chart Review Bose, Mousumi Yergeau, Christine D’Souza, Yasmin Cuthbertson, David D. Lopez, Melisa J. Smolen, Alyssa K. Braverman, Nancy E. Cells Review Zellweger spectrum disorder (ZSD) is a rare, debilitating genetic disorder of peroxisome biogenesis that affects multiple organ systems and presents with broad clinical heterogeneity. Although severe, intermediate, and mild forms of ZSD have been described, these designations are often arbitrary, presenting difficulty in understanding individual prognosis and treatment effectiveness. The purpose of this study is to conduct a scoping review and meta-analysis of existing literature and a medical chart review to determine if characterization of clinical findings can predict severity in ZSD. Our PubMed search for articles describing severity, clinical findings, and survival in ZSD resulted in 107 studies (representing 307 patients) that were included in the review and meta-analysis. We also collected and analyzed these same parameters from medical records of 136 ZSD individuals from our natural history study. Common clinical findings that were significantly different across severity categories included seizures, hypotonia, reduced mobility, feeding difficulties, renal cysts, adrenal insufficiency, hearing and vision loss, and a shortened lifespan. Our primary data analysis also revealed significant differences across severity categories in failure to thrive, gastroesophageal reflux, bone fractures, global developmental delay, verbal communication difficulties, and cardiac abnormalities. Univariable multinomial logistic modeling analysis of clinical findings and very long chain fatty acid (VLCFA) hexacosanoic acid (C26:0) levels showed that the number of clinical findings present among seizures, abnormal EEG, renal cysts, and cardiac abnormalities, as well as plasma C26:0 fatty acid levels could differentiate severity categories. We report the largest characterization of clinical findings in relation to overall disease severity in ZSD. This information will be useful in determining appropriate outcomes for specific subjects in clinical trials for ZSD. MDPI 2022-06-10 /pmc/articles/PMC9221082/ /pubmed/35741019 http://dx.doi.org/10.3390/cells11121891 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bose, Mousumi
Yergeau, Christine
D’Souza, Yasmin
Cuthbertson, David D.
Lopez, Melisa J.
Smolen, Alyssa K.
Braverman, Nancy E.
Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, Meta-Analysis and Medical Chart Review
title Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, Meta-Analysis and Medical Chart Review
title_full Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, Meta-Analysis and Medical Chart Review
title_fullStr Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, Meta-Analysis and Medical Chart Review
title_full_unstemmed Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, Meta-Analysis and Medical Chart Review
title_short Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, Meta-Analysis and Medical Chart Review
title_sort characterization of severity in zellweger spectrum disorder by clinical findings: a scoping review, meta-analysis and medical chart review
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221082/
https://www.ncbi.nlm.nih.gov/pubmed/35741019
http://dx.doi.org/10.3390/cells11121891
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