ABSTRACT
GLUT1 deficiency syndrome (GLUT1DS) is a treatable neurometabolic disorder in which glucose transport into the brain is disturbed. Besides the classic phenotype of intellectual disability, epilepsy, and movement disorders, other phenotypes are increasingly recognized. These include, for example, idiopathic generalized epilepsy and paroxysmal exercise-induced dyskinesia. Since the disorder has only been recognized for two decades and is mostly diagnosed in children, little is known about the disease course. Our purpose was to investigate the disease course of GLUT1DS patients with the classic, complex phenotype from infancy into adulthood. We performed a systematic literature review as well as a cohort study, including GLUT1DS patients aged 18 years and older. The literature search yielded a total of 91 adult GLUT1DS patients, of which 33 patients (one-third) had a complex phenotype. The cohort study included seven GLUT1DS patients with a complex phenotype who were prospectively followed up in our clinic from childhood into adulthood. Our results show that epilepsy is a prominent feature during childhood in classic GLUT1DS patients. During adolescence, however, epilepsy diminishes or even disappears, but new paroxysmal movement disorders, especially paroxysmal exercise-induced dyskinesia, either appear or worsen if already present in childhood. Intellectual disability was not systematically assessed, but cognitive functions appeared to be stabile throughout life. Like children, adolescents may benefit from a ketogenic diet or variants thereof.
