OBJECTIVES: To analyse how the development of an industry-sponsored, but physician directed, multinational database has facilitated collection and interpretation of serial clinical and laboratory observations on patients with Fabry disease – a rare lysosomal storage disorder caused by deficiency of the enzyme a-galactosidase A. METHODS: In 2001, physicians established the operating principles and protocols for collection, retention, retrieval, and analysis of demographic information, signs and symptoms – including laboratory findings – and the response to enzyme replacement therapy with agalsidase alfa in patients with a confirmed diagnosis of Fabry disease. RESULTS: As of December 2007, 190 centres have enrolled 1453 patients from 19 countries worldwide (754 females, 699 males). Of these, 133 are girls and 118 boys less than 18 years of age. Data from these patients have added significantly to our understanding of Fabry disease, with 24 peer-reviewed publications describing the pre-treatment characteristics of the disease and the response to agalsidase alfa. Problems encountered include: 1) incomplete ascertainment of patients with different manifestations of Fabry disease; 2) some systematic lacunae in the data; and 3) uncertainty about the quality of some data. Progress has been made in overcoming these problems by: 1) convening regular meetings of investigators to review protocols, data collection, and findings from data analysis; 2) focusing on ‘core data'; 3) concentrating on achieving comprehensive data collection from centres where enrolment is especially high; and 4) employing clinical research associates to increase data collection and ensure data quality. CONCLUSIONS: FOS has contributed significantly to the understanding of the clinical features of Fabry disease in patients of all ages. Problems with data collection and quality have been addressed by a multi-faceted approach, including focusing on a core panel of data to be collected, together with the use of clinical research associates to check data completeness and quality.