BRAIN MORPHOMETRY ASSOCIATED WITH COGNITIVE AND FINE MOTOR FUNCTIONS IN YOUTH WITH CLASSIC GALACTOSEMIA

Classical galactosemia (CG) is an ultra-rare inherited disorder of metabolism caused by complete deficiency of galactose-1-phosphate uridylyltransferase (GALT) enzyme. Despite early diagnosis and intervention, individuals with CG commonly suffer from cognitive and motor impairments. The present study pioneers surface-based morphometry (SBM) analyses in paediatric patients with CG to investigate the association between cortical alterations and cognitive and fine motor functions. This prospective study included 12 patients with CG (6–20 years) and 12 healthy controls of similar age. T1-weighted magnetic resonance imaging (MRI) was analysed using DL+DiReCT for SBM. Cognitive functioning was evaluated with Wechsler Intelligence Scales; fine motor function using the Purdue Pegboard Test. Multiple linear regression models were applied with bootstrapping and false discovery rate correction. Preliminary results show that patients show alterations in cortical volume, thickness, surface area, and mean curvature compared to healthy controls. For example, medial and inferior frontal cortices demonstrated significantly decreased cortical surface area but significantly increased thickness, indicative of a thickness–surface area trade-off influencing overall volume. Patients displayed consistent patterns of lower cognitive and fine motor performance and greater variability across outcome scores. This study pioneers SBM analyses in paediatric CG patients, revealing cortical alterations associated with functional impairments and elucidating potential neurobiological substrates warranting longitudinal investigation.