Discussion
The prevalence of FD has been reported to be 1 in 40,000 -117,0006 but some sources suggest that as many as 1 in 50,000 males are affected and when late-onset disease is included the incidence may be as high as 1 in 460013,14. The prevalence of FD in patients with ESRD is 0.12-0.70%. Earlier detection would allow for treatment prior to the development of renal disease. Neonatal blood spot screening for Fabry’s is available in some US states and Japan15. This suggest a prevalence of 1 in 12,000 (8,000 if variants of unknown significance considered pathogenic). Screening for FD does not form part of UK neonatal screening protocols.
Most case detection studies for FD have been conducted in patients with significant renal disease or cardiomyopathy. Screening for Fabry’s disease in patients with CKD3b-4 from 0.2-0.6%16-18though some studies fail to find any cases19. A study of the prevalence of FD in a secondary care population under the care of renal specialists is underway in Australia6. However, data on the prevalence in earlier stages of renal disease (not under the care of specialist renal physicians) is lacking. This study found one new female case of FD from 1084 patients (505 male; 579 female) from primary care and non-specialist secondary care based on age-related mild-severe renal disease diagnosed on reduced eGFR. However α-galactosidase activity for females with FD overlaps with the bottom of the normal range resulting in up to 30% false negatives so addition of lysoGL-3 is recommended in females20,21. Enhanced screening with LysoGL-3 biomarker confirmed one female was heterozygous for FD (c.898C>T; p.L300F ; Leu300Phe)22. Further work identified that she was related to a known affected case but had not been contacted for family screening.
The PATHFINDER study pathology-based electronic health record data to identify patients from primary care and non-specialist secondary care mostly CKD stage 2-3(a). This limited this study to use only creatinine (eGFR) data rather than complete renal disease profiles23. No data on albuminuria or (less relevant) haematuria. Albuminuria is considered a useful marker for FD but many early cases of FD lack significant albuminuria24. The cohort sampled was lower risk than previous studies and included both primary and non-specialist secondary care settings. Though underpowered to detect significant numbers of cases, it suggests that enrichment for prior renal disease using a CKD3 cut-off and possibly additional biomarker stratification25 is required before screening for FD is viable.