title: Age adjusting severity scores for Anderson-Fabry disease.
abstract: Anderson-Fabry Disease (AFD) is a life-threatening X-linked lysosomal storage disorder, caused by a deficiency of alpha galactosidase A. The disease affects males and females, and may present in childhood or adulthood. In the absence of a biomarker of disease burden or therapeutic response, scoring systems based on clinical manifestations, have been developed. Such global scores e.g. the Mainz Severity Score Index (MSSI) are confounded by the natural history of disease that deteriorates with age, making comparisons across age groups invalid. In this study the baseline MSSI, as adapted for data collected in the Fabry Outcome Survey (FOS) database (FOS-MSSI), was calculated for 655 females and 617 males with confirmed AFD. Using an ANCOVA model, equations for the predicted FOS-MSSI based on age were derived for males and females from data where patients from the UK or outside Europe were excluded. The initially excluded patients were used for validation. The predicted severity scores of UK and non-Europe-cohorts of adult and paediatric patients were found to follow the model produced for the European cohort thereby providing validation of the methodology. Deviation of the actual FOS-MSSI from the predicted was calculated and termed the age-adjusted score. Examples of the use of the age-adjusted score in individual patients, in comparison of mutations and in investigation of early factors which may impact on later severity of Fabry disease are given. This validated age and gender adjusted scoring system allows the comparison of disease severity in different subgroups such as genotypes without age or sex as confounding factors.
authors.affiliation: Lysosomal Storage Disorders Unit, Royal Free Hospital, London, UK. d.hughes@medsch.ucl.ac.uk
authors.forename: D A
authors.initials: DA
authors.lastname: Hughes
authors.forename: U
authors.initials: U
authors.lastname: Ramaswami
authors.forename: M-Á
authors.initials: MÁ
authors.lastname: Barba Romero
authors.forename: P
authors.initials: P
authors.lastname: Deegan
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D000795:Fabry Disease / Q000145:classification / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index