Background Anderson-Fabry disease (AFD) is a disorder of glycosphingolipid metabolism resulting from deficiency of α-galactosidase A and accumulation of globotriaosylceramide. Presentation is heterogeneous and, despite guidelines for initiation of therapy, there is no basis for defining subgroups that will progress more rapidly, whether treated or not. The authors of this study used clinical and pathological data recorded on 1483 patients in the Fabry Outcome Survey, a large international registry, to develop a prognostic severity score.
Methods Parameters relevant to disease progression or outcome were initially selected, using variables that are readily available in clinical practice. Individual end points for renal, cardiac, neurological disease, and death were selected, and a composite end point developed. Potential prognostic variables were correlated with each end point, before multivariate analysis. Variables retaining significance were then used to construct organ specific and composite prognostic scores. Kaplan–Meier (KM) analysis, according to score, was performed for each end point.
Results Analysis demonstrated that it is possible to differentiate groups of patients with different outcome probabilities. Cardiac, renal and neurological end points could each be categorised into three separate groups. The 80% event-free survival for these groups differed by approximately 10 years. The overall composite score, the Fabry International Prognostic Index (FIPI), distinguished two distinct groups where the 50% event-free survival differed by 10 years.
Conclusions A prognostic scoring system for AFD has been developed and retrospective validation performed. The FIPI should prove to be a valuable tool in the counselling and management of AFD patients, and in comparative analyses of outcome using different therapies.
- academic medicine
- calcium and bone
- cell biology
- clinical genetics
- cardiovascular medicine
- renal medicine
- metabolic disorders
- molecular genetics
- clinical genetics
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Funding Shire HGT sponsors the Fabry Outcome Survey (FOS) and supported statistical analysis. No other funding was received.
Competing interests DAH has received travel, educational and research grants and honoraria for speaking and advisory boards from Shire HGT, Genzyme Inc and Amicus therapeutics. UR has received travel, and research grants and honoraria for speaking and advisory boards from Shire HGT and Genzyme Inc. LG has received travel bursaries and honoraria for speaking and advisory boards from Shire HGT. CO has received travel bursaries and honoraria for speaking from Shire HGT. CJ has received honoraria for advisory boards from Shire HGT. GMP has received honoraria, research funding, and/or travel expenses from Shire HGT, Genzyme, and Amicus. MW has received honoraria, research funding, speaker's fees, and/or travel expenses from Shire HGT, Genzyme, and Amicus. PBD has received speaker fees, travel grants and research support from Shire HGT. PE has received speaker fees, funding for symposium attendance, and unrestricted educational grants from Shire HGT and Genzyme. M Malmenäs (MM), statistician, is an employee of Shire HGT. FOS is an international database of treated and untreated Fabry patients supported financially by Shire HGT. Shire HGT did not have any role in the conception, design or execution of this study outside of statistical support (MM) and its role in the support of the database. No writing support was received for this study. No honoraria were received in connection with the writing of this study.
Patient consent Patients signed ethics committee approved consent forms to participate in the study.
Ethics approval Institutional review board for each participating centre (UK MREC Cambridge).
Provenance and peer review Not commissioned; externally peer reviewed.