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 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.

• Authors: Anna Ka-Yee Kwong, Virginia Chun-Nei Wong, Sheila Suet-Na Wong, Vanessa Loi-Yan Chu, Saskia Koene, Jan Smeitink, Cheuk-Wing Fung
• Journal: Epilepsia open (Epilepsia Open) Vol. 6 Issue 4 Pg. 685-693 (12 2021) ISSN: 2470-9239 [Electronic] United States
• PMID: 34379890 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.

Chemical References

• FGF21 protein, human
• fibroblast growth factor 21
• Fibroblast Growth Factors

Topics

• Epilepsies, Myoclonic (drug therapy, genetics)
• Fibroblast Growth Factors (blood)
• Humans
• Infant
• Retrospective Studies
• Seizures (genetics)
• Spasms, Infantile