Sanfilippo syndrome (mucopolysaccharidosis type III or MPS III ) is a lysosomal storage disorder characterized by progressive mental deterioration and behavioral problems with only mild somatic disease. Sanfilippo type C in 2006 the gene encoding enzyme acetyl-CoA: alpha-glucosaminide N-acetyltransferase was cloned and localized to chromosome 8 p11.1. Sanfilippo syndrome includes destructiveness, restlessness, and aggressiveness and sleep problems. Aggression and hyperactivity respond poorly to behavioral treatment. Progressive behavioral problems are predominant symptom in Sanfilippo patients. Behavioral problems usually start around the age of 3-5 years and consist of restless, destructive, chaotic, anxious and sometimes aggressive behavior. Behavioral problems decline with age and eventually disappear due to the progressive mental retardation, finally resulting in complete loss of initiative. Drug treatment aimed at controlling the hyperactivity and aggression is necessary to allow many families to cope. The response to such treatment is very unpredictable and parents should be warned that a temporary worsening of behaviors might follow the introduction of any antipsychotic agent. A 12-year-old girl was presented with hyperactivity and restlessness and behavioral problems. At age of 8, the adolescent was treated with 0.5 mg/day risperidone because of agitation, restlessness, and temper tantrums. At 11-year-old girl was diagnosed as having Sanfilippo type c with the clinical presentation consisting of coarse faces, hepato/splenomegalia; dysostosis multiplex, neurocognitive deficit, hypertrychosis, family history of positive similar affected late male cousin. When the adolescent was 11 years old, atomoxetine 20 mg/day treatment was began due to hyperactivity, and as the behavioral problems continued, atomoxetine was stopped and aripiprazole 2.5 mg/day was started. 4 days later, the patient developed akathisia and extrapyramidal side effect and aripiprazole was discontinued. During the follow up, the patient continued taking şuoxetine 10 mg /day because of restlessness and crying. Complaints decreased but since hyperactivity and talking too much persisted, methylphenidate was added on present drug treatment and improvement was observed. The Sanfilippo syndrome is particularly hard on families, because the progressive mental retardation is often accompanied by intense hyperactivity that is not readily managed with medications. Our case is notable because conventional treatment, including behavioral modification and pharmacotherapy including stimulants and most of antipsychotics has provided limited success in managing behavioral problems.