Children with mucopolysaccharidosis IIIA (MPS-IIIA) may receive a diagnosis of autism spectrum disorder (ASD) due to MPS-IIIA's initial symptom similarities with ASD. This may lead to professionals receiving referrals to work with these children but unaware of how these children may respond differently to treatment. To appropriately work with these children, clinicians must obtain knowledge of the symptoms, progressions, regression, comorbidities, and clinical interventions. This manuscript guides clinicians on the discrimination of MPS-IIIA from ASD for (a) physiological symptoms, (b) skill development and regression of skills, and (c) behavior problems from infancy to adolescence. The manuscript also provides available intervention research.