High FGF‐21 level in a cohort of 22 patients with Dravet Syndrome—Possible relationship with the disease outcomes

Abstract Objective Dravet syndrome (DS) is a severe and intractable form of epilepsy with prolonged seizures which may evolve to other seizure types and associated with mild‐to‐severe intellectual disabilities. Fibroblast growth factor 21 (FGF‐21) is a stress hormone mediating metabolic and oxidativ...

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Autores principales:	Anna Ka‐Yee Kwong, Virginia Chun‐Nei Wong, Sheila Suet‐Na Wong, Vanessa Loi‐Yan Chu, Saskia Koene, Jan Smeitink, Cheuk‐Wing Fung
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	dravet syndrome epileptic encephalopathy FGF‐21 fibroblast growth factor 21 mitochondrial oxidative phosphorylation valproate Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/ade30fff07e044ef82b2ff57c48f25fe
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spelling	oai:doaj.org-article:ade30fff07e044ef82b2ff57c48f25fe2021-12-01T06:09:19ZHigh FGF‐21 level in a cohort of 22 patients with Dravet Syndrome—Possible relationship with the disease outcomes2470-923910.1002/epi4.12534https://doaj.org/article/ade30fff07e044ef82b2ff57c48f25fe2021-12-01T00:00:00Zhttps://doi.org/10.1002/epi4.12534https://doaj.org/toc/2470-9239Abstract Objective Dravet syndrome (DS) is a severe and intractable form of epilepsy with prolonged seizures which may evolve to other seizure types and associated with mild‐to‐severe intellectual disabilities. Fibroblast growth factor 21 (FGF‐21) is a stress hormone mediating metabolic and oxidative stress and circulating level of FGF‐21 had been shown to increase in some patients with impairment of oxidative phosphorylation in muscles. In DS, FGF‐21 is of interest for further study as mitochondrial oxidative stress was identified previously in patients. Methods Plasma FGF‐21 levels were compared between 22 DS patients and 22 normal controls, and their clinical characteristics of DS patients at the time of plasma sampling were studied retrospectively. Besides, the relationships of FGF‐21 level with intellectual development, seizure frequency, valproate treatment, and types of SCN1A mutations were analyzed. Logarithmic transformation of FGF‐21 levels was performed before comparison and statistical analysis. Results Mean of log10 FGF‐21 level was significantly higher in DS patients when comparing with normal controls (P = .0042). Mean of log10 FGF‐21 level was significantly higher in DS patients with normal‐to‐mild ID versus mild‐to‐severe ID (P = .0193) and with valproate treatment versus without valproate treatment (P = .015). No significant difference was shown in FGF‐21 level in DS patients with missense versus truncating SCN1A variants, and no correlation could be demonstrated between seizure frequency and FGF‐21 level. Significance Significantly higher level of plasma FGF‐21 was identified in DS patients. The high FGF‐21 levels were shown to be associated with developmental outcome and valproate treatment. These results support further investigation on the relationship of FGF‐21 with the clinical outcomes of DS and other related mechanism which is important for possible therapeutic development for this epileptic encephalopathy.Anna Ka‐Yee KwongVirginia Chun‐Nei WongSheila Suet‐Na WongVanessa Loi‐Yan ChuSaskia KoeneJan SmeitinkCheuk‐Wing FungWileyarticledravet syndromeepileptic encephalopathyFGF‐21fibroblast growth factor 21mitochondrial oxidative phosphorylationvalproateNeurology. Diseases of the nervous systemRC346-429ENEpilepsia Open, Vol 6, Iss 4, Pp 685-693 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dravet syndrome epileptic encephalopathy FGF‐21 fibroblast growth factor 21 mitochondrial oxidative phosphorylation valproate Neurology. Diseases of the nervous system RC346-429
spellingShingle	dravet syndrome epileptic encephalopathy FGF‐21 fibroblast growth factor 21 mitochondrial oxidative phosphorylation valproate Neurology. Diseases of the nervous system RC346-429 Anna Ka‐Yee Kwong Virginia Chun‐Nei Wong Sheila Suet‐Na Wong Vanessa Loi‐Yan Chu Saskia Koene Jan Smeitink Cheuk‐Wing Fung High FGF‐21 level in a cohort of 22 patients with Dravet Syndrome—Possible relationship with the disease outcomes
description	Abstract Objective Dravet syndrome (DS) is a severe and intractable form of epilepsy with prolonged seizures which may evolve to other seizure types and associated with mild‐to‐severe intellectual disabilities. Fibroblast growth factor 21 (FGF‐21) is a stress hormone mediating metabolic and oxidative stress and circulating level of FGF‐21 had been shown to increase in some patients with impairment of oxidative phosphorylation in muscles. In DS, FGF‐21 is of interest for further study as mitochondrial oxidative stress was identified previously in patients. Methods Plasma FGF‐21 levels were compared between 22 DS patients and 22 normal controls, and their clinical characteristics of DS patients at the time of plasma sampling were studied retrospectively. Besides, the relationships of FGF‐21 level with intellectual development, seizure frequency, valproate treatment, and types of SCN1A mutations were analyzed. Logarithmic transformation of FGF‐21 levels was performed before comparison and statistical analysis. Results Mean of log10 FGF‐21 level was significantly higher in DS patients when comparing with normal controls (P = .0042). Mean of log10 FGF‐21 level was significantly higher in DS patients with normal‐to‐mild ID versus mild‐to‐severe ID (P = .0193) and with valproate treatment versus without valproate treatment (P = .015). No significant difference was shown in FGF‐21 level in DS patients with missense versus truncating SCN1A variants, and no correlation could be demonstrated between seizure frequency and FGF‐21 level. Significance Significantly higher level of plasma FGF‐21 was identified in DS patients. The high FGF‐21 levels were shown to be associated with developmental outcome and valproate treatment. These results support further investigation on the relationship of FGF‐21 with the clinical outcomes of DS and other related mechanism which is important for possible therapeutic development for this epileptic encephalopathy.
format	article
author	Anna Ka‐Yee Kwong Virginia Chun‐Nei Wong Sheila Suet‐Na Wong Vanessa Loi‐Yan Chu Saskia Koene Jan Smeitink Cheuk‐Wing Fung
author_facet	Anna Ka‐Yee Kwong Virginia Chun‐Nei Wong Sheila Suet‐Na Wong Vanessa Loi‐Yan Chu Saskia Koene Jan Smeitink Cheuk‐Wing Fung
author_sort	Anna Ka‐Yee Kwong
title	High FGF‐21 level in a cohort of 22 patients with Dravet Syndrome—Possible relationship with the disease outcomes
title_short	High FGF‐21 level in a cohort of 22 patients with Dravet Syndrome—Possible relationship with the disease outcomes
title_full	High FGF‐21 level in a cohort of 22 patients with Dravet Syndrome—Possible relationship with the disease outcomes
title_fullStr	High FGF‐21 level in a cohort of 22 patients with Dravet Syndrome—Possible relationship with the disease outcomes
title_full_unstemmed	High FGF‐21 level in a cohort of 22 patients with Dravet Syndrome—Possible relationship with the disease outcomes
title_sort	high fgf‐21 level in a cohort of 22 patients with dravet syndrome—possible relationship with the disease outcomes
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/ade30fff07e044ef82b2ff57c48f25fe
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High FGF‐21 level in a cohort of 22 patients with Dravet Syndrome—Possible relationship with the disease outcomes

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