Mucopolysaccharidoses (MPS) type III also termed as Sanfillipo syndrome, involves defect in enzymes required for degradation of heparan sulphate. We report a clinical case of MPS-III later followed by genetic investigation for MPS-III genes SGSH , NAGLU , HGSNAT and GNS. It allowed us to identify a novel and likely pathogenic variant p. G205R in SGSH . Protein based Inslico prediction and protein modelling suggests aberration of helical structure of SGSH protein and reduced binding affinity for its substrate.