Fabry International Prognostic Index: a predictive severity score for Anderson-Fabry disease.
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.
Lysosomal Storage Disorders Unit, Department of Haematology, Royal Free Campus, University College London, London, UK. rmgvdah@ucl.ac.uk
Derralynn A
DA
Hughes
Mia
M
Malmenäs
Patrick B
PB
Deegan
Perry M
PM
Elliott
Lionel
L
Ginsberg
Daniel
D
Hajioff
Alex S
AS
Ioannidis
Catherine H
CH
Orteu
Uma
U
Ramaswami
Michael
M
West
Gregory M
GM
Pastores
Crispin
C
Jenkinson
D000328:Adult; D004252:DNA Mutational Analysis; D000795:Fabry Disease / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020125:Mutation, Missense; D011379:Prognosis; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D055815:Young Adult