OBJECTIVES:Alpha-mannosidosis (AM) is a rare, lysosomal storage disease (LSD), caused by deficient activity of the lysosomal enzyme alpha-mannosidase. AM is a slowly progressive disease with substantial inter-patient heterogeneity in the onset of symptoms and domains’ afflicted. A broad range of clinical features are associated with AM including impairment to the musculoskeletal, neurological, respiratory and immunological systems, which lead to cumulative effects on patients’ health. AM is therefore associated with a substantial burden to both patients and caregivers, as well as significant costs relating to symptomatic treatment, healthcare resource utilisation, and loss of productivity. As an ultra-orphan disease, it is challenging to provide an accurate estimate of the prevalence and incidence of AM. The objective of this systematic review (SR) was to identify epidemiological data related to AM. METHODS: A SR was performed in March 2017 to identify published evidence on the incidence and prevalence of AM. Searches were conducted in MEDLINE, Embase, the Cochrane library and the alpha-Mannosidosis Mutation Database. RESULTS: A total of 15 publications (14 unique studies) were identified in the SR. Incidence data were reported for twelve countries; the overall incidence of AM ranged from 0.07 (Sweden) to 1.51 (United Arab Emirates [UAE]) per 100,000 live births. For studies reporting an absolute number of AM cases over a given time period (10 studies), estimates ranged from 0.1 (Canada/Sweden) to 1.7 (Russia) AM cases per year per country. The AM Mutation Database reported a total of 191 AM patients worldwide. CONCLUSIONS: Published data indicate that the overall incidence of AM globally ranged from 0.07 to 1.51 per 100,000 births. A higher incidence of AM was reported in Cuba and UAE. The present SR identified a limited number of AM epidemiological studies, indicating that further research is required to fully characterise the epidemiology of AM.