Scoring system to facilitate diagnosis of Gaucher disease.

BACKGROUND: Gaucher disease (GD) manifests heterogeneously and other conditions are often misdiagnosed in its place, leading to diagnostic delays. The Gaucher Earlier Diagnosis Consensus (GED-C) initiative proposed a point-scoring system (PSS) based on the signs and covariables that are most indicative of GD to help clinicians identify which individuals to test for GD. AIMS: To validate the PSS retrospectively in a test population including patients with GD and other conditions with overlapping manifestations. METHODS: Four cohorts of adults with GD, liver disease, haematological malignancy or immune thrombocytopenia were identified from hospital records. Clinical data were audited for GED-C factors identified as potentially indicative of GD and aggregate scores calculated (sum of scores/number of factors) based on published PSS weightings. Threshold discriminatory PSS scores, sensitivity and specificity were determined by receiver-operating characteristic analysis. RESULTS: Among 100 patients (GD, n = 25; non-GD, n = 75), analyses based on 11 possible factors estimated group mean (standard deviation) PSS scores of: GD (n = 14), 1.08 (0.25); non-GD (n = 38), 0.58 (0.31). Mean between-group difference (95% confidence interval) was -0.49 (-0.68, -0.31) and area under the receiver-operating characteristic analysis curve (95% confidence interval) was 0.88 (0.78, 0.97). A threshold PSS score of 0.82 identified all 14 patients with GD in the analysis set (100% sensitivity) and 27 of 38 patients in the non-GD group (71% specificity). Patients with liver disease and haematological malignancy were most likely to have manifestations overlapping GD. CONCLUSIONS: Preliminary validation of the GED-C PSS discriminated effectively between patients with GD and those with overlapping signs.

Early indicators of disease progression in Fabry disease that may indicate the need for disease-specific treatment initiation: findings from the opinion-based PREDICT-FD modified Delphi consensus initiative.

OBJECTIVES: The PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease (PREDICT-FD) initiative aimed to reach consensus among a panel of global experts on early indicators of disease progression that may justify FD-specific treatment initiation. DESIGN AND SETTING: Anonymous feedback from panellists via online questionnaires was analysed using a modified Delphi consensus technique. Questionnaires and data were managed by an independent administrator directed by two non-voting cochairs. First, possible early indicators of renal, cardiac and central/peripheral nervous system (CNS/PNS) damage, and other disease and patient-reported indicators assessable in routine clinical practice were compiled by the cochairs and administrator from panellists' free-text responses. Second, the panel scored indicators for importance (5-point scale: 1=not important; 5=extremely important); indicators scoring ≥3 among >75% of panellists were then rated for agreement (5-point scale: 1=strongly disagree; 5=strongly agree). Indicators awarded an agreement score ≥4 by >67% of panellists achieved consensus. Finally, any panel-proposed refinements to consensus indicator definitions were adopted if >75% of panellists agreed. RESULTS: A panel of 21 expert clinicians from 15 countries provided information from which 83 possible current indicators of damage (kidney, 15; cardiac, 15; CNS/PNS, 13; other, 16; patient reported, 24) were compiled. Of 45 indicators meeting the importance criteria, consensus was reached for 29 and consolidated as 27 indicators (kidney, 6; cardiac, 10; CNS/PNS, 2; other, 6; patient reported, 3) including: (kidney) elevated albumin:creatinine ratio, histological damage, microalbuminuria; (cardiac) markers of early systolic/diastolic dysfunction, elevated serum cardiac troponin; (CNS/PNS) neuropathic pain, gastrointestinal symptoms suggestive of gastrointestinal neuropathy; (other) pain in extremities/neuropathy, angiokeratoma; (patient-reported) febrile crises, progression of symptoms/signs. Panellists revised and approved proposed chronologies of when the consensus indicators manifest. The panel response rate was >95% at all stages. CONCLUSIONS: PREDICT-FD captured global opinion regarding current clinical indicators that could prompt FD-specific treatment initiation earlier than is currently practised.