Mucopolysaccharidosis type IIIA (MPS-IIIA) is a rare genetic metabolism disorder, belonging to the class of Lysosomal Storage Disorders (LSD). MPS-IIIA is caused by a mutation in the gene SGSH, leading to lysosomal enzyme sulfamidase deficiency and impaired degradation of heparan sulfate. Although the disease manifests during early childhood as an autistic spectrum disorder (ASD), the causes of ASD in MPS-IIIA are only poorly explored. Using a genetic mouse model of MPS-IIIA, we have recently discovered that these autistic-like behavioural symptoms (ALBs), which are known to be subtly regulated by dopaminergic pathways, are due to an increased number of dopaminergic progenitors during prenatal life. This expansion persists postnatally and into adulthood at the level of the mesencephalon. In the striatum, the brain hub for dopamine, adult MPS-IIIA mice show an increased volume, increased dopamine content and imbalance in the expression of dopamine receptors, ultimately leading to an hyperactivation of D1 receptors direct pathway and hypoactivation of D2 receptors indirect pathway (1). Since striatal development ends postnatally and involves synaptic pruning, an autophagy-related process that eliminates excess neuronal connections (2), we investigated synaptic pruning in MPS-IIIA mice. Interestingly, we found an increase in dendritic spine density, in the dendritic width and in the cellular body dimension in the striatum of MPS-IIIA mice during the main stage of postnatal striatal development. Defective synaptic pruning might underlie striatal overgrowth, enlightening a possible mechanism behind ALBs in MPS-IIIA. Moreover it might have broader implications for other LSDs with defective HS-related genes that lead to autism.