Age adjusting severity scores for Anderson-Fabry disease

Area of Science:

• Genetics and Genetic Diseases
• Metabolic Disorders
• Biochemistry

Background:

• Anderson-Fabry Disease (AFD) is a severe X-linked lysosomal storage disorder due to alpha galactosidase A deficiency.
• Current scoring systems like the Mainz Severity Score Index (MSSI) are confounded by age-related disease progression, limiting comparisons.
• There is a need for a reliable biomarker or scoring system to assess disease burden and therapeutic response in AFD.

Purpose of the Study:

• To develop and validate an age- and gender-adjusted scoring system for Anderson-Fabry Disease severity.
• To overcome the limitations of existing global scores that are confounded by patient age.
• To enable valid comparisons of disease severity across different subgroups, such as genotypes.

Main Methods:

• Calculated the Fabry Outcome Survey-Mainz Severity Score Index (FOS-MSSI) for 655 females and 617 males with confirmed AFD.
• Utilized an ANCOVA model to derive age-based prediction equations for FOS-MSSI in males and females, excluding UK/non-European cohorts initially.
• Validated the model using previously excluded UK and non-European patient data, calculating an 'age-adjusted score' as the deviation from the predicted FOS-MSSI.

Main Results:

• Developed validated age- and gender-adjusted prediction equations for FOS-MSSI.
• Demonstrated that UK and non-European cohorts followed the derived European cohort model, confirming methodology validation.
• Introduced the 'age-adjusted score' to quantify disease severity independent of age and gender.

Conclusions:

• The validated age- and gender-adjusted scoring system enables accurate comparison of AFD severity across subgroups.
• This new scoring system can be used to compare genotypes and investigate early factors influencing later disease severity.
• The age-adjusted score addresses the confounding effects of age and sex in AFD severity assessment.