GLUT1 deficiency syndrome in adulthood: lost in diagnosis

Background: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare genetic disorder impairing cerebral glucose transport, leading to variable neurological symptoms in which adult care remains underexplored. This study aims to characterise adult phenotypes, identify unmet needs and inform a person-centred care model. Methods: 32 adults with genetically confirmed GLUT1DS were retrospectively evaluated at two centres in Milan, Italy. Clinical history, diagnostic data, treatment and follow-up information were systematically collected. 19 patients underwent extended assessments including cognitive, neuropsychiatric, sleep, adaptive functioning and quality of life evaluations. Nine also participated in psychological interviews. Results: The cohort included 68.8% female (median age: 32 years). Median age at symptom onset was 2 years, with a diagnostic delay of 18 years. 62% of individuals received a diagnosis in adulthood, with 31% diagnosed only after their child was identified. Except for two cases, all exhibited in their clinical history typical GLUT1DS symptoms that were either unrecognised or too mild to prompt medical attention. Psychosocial health issues were identified in 42% of cases, with emotional disturbances affecting 53% and social life impairments in 42%; physical health concerns in 32%. Conclusions: Diagnostic delay in adults with GLUT1DS is more likely due to limited clinical awareness than to atypical presentations. The most effective model of care for individuals with GLUT1DS might be multidisciplinary involving paediatric and adult neurologists, rehabilitation professionals, clinical psychologists, clinical nutritionists and dietitians to support motor, cognitive and emotional functioning, thereby promoting autonomy, improving quality of life and addressing challenges associated with ketogenic diet adherence.