Females and children with Anderson-Fabry disease: diagnosis, monitoring, benefits of enzyme replacement therapy (ERT) and considerations on timing of starting ERT

Introduction: Anderson-Fabry disease (AFD) is a hereditary disorder caused by lysosomal enzyme a-galactosidase A deficiency, previously thought to affect adult males only. Recently, it has become clear that women and children are also affected. Clinical data for enzyme replacement therapy (ERT) show that the two available agents, agalsidase alpha and beta, improve or stabilize AFD in men; however, data in women and children are limited. Areas covered: The authors review AFD clinical phenotype and ERT clinical data, and discuss the timing of ERT initiation in women and children. Clinical trials and registry data were found from PubMed literature searches using search terms 'Anderson-Fabry disease' AND 'enzyme replacement therapy' AND 'children/paediatric' OR 'women/female'. Papers were selected manually from the search results. Expert opinion: Doubts remain about the correct time to start treatment in women and children. Early treatment is supported by the observation that ERT effects are reduced in advanced AFD. However, pre-symptomatic ERT does not appear to be advocated, unless, in an individual patient, a marked improvement in QoL would be achieved. Tools to identify those who are likely to progress to overt disease are required. Currently, assessment of disease burden entails accurate and detailed evaluation by AFD-related specialists.