Fabry Disease Patient-Reported Outcome (FD-PRO) demonstrates robust measurement properties for assessing symptom...

Fabry disease (FD) is a rare, genetic disease, that if untreated, progresses to irreversible and life-threatening renal, cardiac, and cerebrovascular events. FD symptoms impact daily functioning and quality of life, but no disease-specific measure of these symptoms has been psychometrically tested.

The Fabry Disease Patient-Reported Outcome (FD-PRO) consists of 19 items that measure neuropathic symptoms (pain, tingling, numbness and burning in upper/lower extremities), headache, abdominal pain, heat intolerance, swelling, tinnitus, fatigue, hearing/vision impairment, hypohidrosis (diminished sweating) and difficulty engaging in regular physical activities in the past 24 h. Measurement properties of the instrument were evaluated among 139 adult (≥ 18 years) FD diagnosed patients (enzyme deficiency in males; GLA genotyping in females) including enzyme replacement (ERT) treated or treatment-naïve patients, classic or late-onset phenotypes from ten countries and eighteen sites. Patients completed the FD-PRO daily on a handheld electronic diary for 4 weeks; demographic, other patient and clinician reported outcomes were also collected.

The mean age of patients was 43 years; with even sex distribution (female: 53%) and majority was ERT treated (72%). Patient compliance was high; ≥ 87% completed at least 4 FD-PRO entries each week (mean completion time: < 3 min in week one). Empirical evaluation of item properties via inter-item correlations, exploratory factor analysis and item-response theory models suggested that a total symptom score (TSS) could be calculated. Due to redundancy among items, a "neuropathy parcel" and an "audiovisual parcel" were created in generating the TSS (items within a parcel averaged and treated as a single item). Two items were excluded from TSS: sweating (did not correlate with other items) and difficulty engaging in regular physical activities (measure of impact, not symptoms). Internal consistency (Cronbach's alpha) of the TSS was ≥0.89 across weeks; test-retest reliability (intraclass correlation coefficient) was ≥0.91. The TSS was correlated with conceptually similar clinical and patient reported assessments as expected (r > |0.4|) and discriminated moderate/severe from least severe FD groups in known-groups validity analyses.

The FD-PRO instrument is a novel disease-specific instrument that assesses classic and non-classic symptoms, with strong psychometric properties and appropriate for use in clinical studies.