A global consensus on early indicators of organ damage in Fabry disease and implications for treatment initiation

Diagnostic delays are common in Fabry disease (FD), and initiation of disease-specific therapy is only recommended in certain patients at diagnosis. Timely treatment of FD is critical to mitigate or prevent organ damage. Earlier treatment could be facilitated if physicians knew which early indicators of organ involvement in FD are most predictive of later damage. In round 1 of an anonymous, iterative, three-round Delphi process, a panel of 21 expert physicians, from 15 countries, were asked independently to list early indicators of organ damage that can be readily assessed and that might merit initiation of disease-specific therapy an independent administrator collated the responses. In round 2, each panel member rated each indicator for importance on a 5-point Likert scale (1=not important to 5=extremely important). Indicators rated most important (a score of ≥3 assigned by >75% of respondents) were reissued to the panel in round 3 for agreement rating using a 5-point Likert scale (1=strongly agree to 5=strongly disagree). Consensus was achieved for an indicator if >67% of respondents rated their agreement ≥4. Based on responses in round 1, the panel (100% response rate) voted on 15 renal, 15 cardiac, 13 CNS, 24 patient-reported and 16 other indicators. In round 2, 7 renal, 12 cardiac, 5 CNS, 13 patient-reported and 8 other indicators were deemed most important. In round 3, consensus was reached on 6 renal, 10 cardiac, 2 CNS, 6 patient-reported and 5 other indicators. At least 90% of the panel agreed that: elevated albumin:creatinine ratio or microalbuminuria histological evidence of renal involvement minor abnormalities of glomerular filtration rate markers of early systolic/diastolic dysfunction neuropathic pain and pain in the extremities/neuropathy, were important early indicators of organ damage. Findings from this consensus initiative may guide early appropriate disease-specific therapy initiation in FD.