OBJECTIVES: To estimate long-term disability costs associated with tuberous sclerosis complex, a rare multisystem  genetic disease, in Brazil METHODS: Literature review for TSC long-term disability and economic burden was performed (Pubmed, LILACS, SciELO, CRDs).  Cost estimation was limited to  epilepsy (most prevalent TSC disorder). Cost of lost productivity in patients since  epilepsy onset in childhood and carried in adulthood as well as caregivers’ productivity costs were estimated. The Human Capital Method was adopted and potential lost working years estimated till an active age of 65 years. It was assumed a caregiver for all ages. Average income, unemployment rate due to epilepsy, productivity growth and epidemiology data were obtained from the literature and from the Brazilian Institute of Geography and Statistics. Mean annual productivity cost per patient, total productivity cost per patient and the total productivity burden of TSC-related epilepsy were calculated. Costs were estimated in 2008 Reals and discounted at 5%. Univariate sensitivity analysis was conducted for epidemiology data, employment status rate, productivity growth, discount rate and time horizon. RESULTS: Productivity loss was 47, 30 and 65 years for epilepsy onset in childhood and adulthood and caregivers, respectively. The discounted and not discounted mean annual productivity cost per patient were R$1,970 and R$11,323, total productivity cost per patient R$97,882 and R$691,150 and total productivity burden of TSC-related epilepsy in Brazil R$1,568,965,961 and R$11,078,536,271, respectively (1Euro= 3.24Reals). Results were sensitive to all the parameters varied in the sensitivity analysis, especially discount rate. CONCLUSIONS: TSC-related epilepsy is a chronic disorder associated with loss of productivity with a significant economic burden in Brazil. Although significant, the economic burden related to productivity loss is expected to be even higher since there are still costs deriving from absenteeism of patients and caregivers when employed looking for health services to be included in further analysis.