Open AccessHigh FGF‐21 level in a cohort of 22 patients with Dravet Syndrome—Possible relationship with the disease outcomes
Author(s) -
Kwong Anna KaYee,
Wong Virginia ChunNei,
Wong Sheila SuetNa,
Chu Vanessa LoiYan,
Koene Saskia,
Smeitink Jan,
Fung CheukWing
Publication year - 2021
Publication title -
epilepsia open
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.247
H-Index - 16
ISSN - 2470-9239
DOI - 10.1002/epi4.12534
Subject(s) - dravet syndrome , medicine , oxidative stress , fibroblast growth factor , fgf21 , epilepsy , endocrinology , cohort , gastroenterology , receptor , psychiatry
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 log 10 FGF‐21 level was significantly higher in DS patients when comparing with normal controls ( P = .0042). Mean of log 10 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.