OBJECTIVE: Characterizing morbidity and mortality in rare genetic diseases is challenging given the small numbers of patients, their wide geographic distribution, and the variable effects of genetic mutations. Global natural history studies aim to close the knowledge gap but require the participation of multiple countries to achieve this goal. METHODS: In 2006, Genzyme Corporation initiated a retrospective natural history feasibility study of acid sphingomyelinase deficiency (ASMD, also known as Niemann Pick disease Types A and B) in 8 Eurasian countries. ASMD is an inherited lysosomal storage disorder that affects approximately 2000 patients in developed countries and has no specific treatment. The goal of the study was to determine whether investigators would be able to implement a medical record abstraction study of ASMD. The objective of the post-feasibility study is to provide improved estimates of morbidity and mortality that can help facilitate drug development. RESULTS: Eurasian investigators were enthusiastic about participating in and improving knowledge on this rare and life-threatening disease, but they were cautious about interpreting existing/evolving regulations for each country. Some countries use the European Directive (ED) 2001/20/EC to govern all research (e.g. Germany regional EC), others are in an “evolving process” of coming into “adapted” compliance with the ED (e.g. France); and others have their own independent regulations that are less accessible (e.g. Saudi Arabia). Each country has varying data protection legislation. CONCLUSIONS: For some, regulatory approvals are believed to be easier to acquire from disparate regulatory bodies when no intervention is under study. However, investigators cautioned that their various regulatory authorities do not support natural history studies if they appear to be “large cheap databases” driven by outside countries. More support for such studies is likely if the natural history data serves as an untreated control arm when treatments begin to be tested.