The Impact of Puberty on Children With GLUT1 Deficiency Syndrome.

BACKGROUND

GLUT1 deficiency syndrome (GLUT1DS) is an autosomal dominant disorder caused by variants in the SLC2A1 gene in which children have epilepsy and movement disorders. Similar to other children with neurological conditions, parents of patients are often concerned about the impact of puberty on clinical features.

METHODS

A survey was made available on the internet in January 2025 to all members of the GLUT1DS community. Responses were anonymous and collected by the Glut1 Deficiency Foundation; parents or adolescents/adults could participate. Inclusion criteria included a GLUT1DS diagnosis and having undergone puberty.

RESULTS

Ninety-eight surveys were completed. Seizures worsened during puberty in 38. Contrarily, 58% had worsening of movement abnormalities, with treatments including acetazolamide, clonazepam, gabapentin, and clobazam. Additional symptoms included migraines (35%) and mood swings (38%), with more of the former in girls (44% vs 18%, P = 0.01). In those who experience menses, 71% have a change in symptoms during this time and about half have changes in ketosis levels. Seventy-two were on ketogenic diet therapy during puberty. Of those who checked ketones, 42 of 49 (86%) had decreased levels during puberty; however, only 42% of these children had increased seizures. There was no difference between ketogenic diet therapies in terms of ketosis, compliance, seizures, or movements.

CONCLUSIONS

Puberty in GLUT1DS was most likely to worsen movement disorders, but about one third also had increased seizures and the onset of migraines and mood swings. For those on a ketogenic diet, although ketosis often decreases, this was not uniformly associated with more seizures.