Presenting signs and patient co‐variables in Gaucher disease: outcome of the Gaucher Earlier Diagnosis Consensus (GED‐C) Delphi initiative

Abstract

BackgroundGaucher disease (GD) presents with a range of signs and symptoms. Physicians can fail to recognise the early stages of GD owing to a lack of disease awareness, which can lead to significant diagnostic delays and sometimes irreversible but avoidable morbidities.AimThe Gaucher Earlier Diagnosis Consensus (GED‐C) initiative aimed to identify signs and co‐variables considered most indicative of early type 1 and type 3 GD, to help non‐specialists identify ‘at‐risk’ patients who may benefit from diagnostic testing.MethodsAn anonymous, three‐round Delphi consensus process was deployed among a global panel of 22 specialists in GD (median experience 17.5 years, collectively managing almost 3000 patients). The rounds entailed data gathering, then importance ranking and establishment of consensus, using 5‐point Likert scales and scoring thresholds defined a priori.ResultsFor type 1 disease, seven major signs (splenomegaly, thrombocytopenia, bone‐related manifestations, anaemia, hyperferritinaemia, hepatomegaly and gammopathy) and two major co‐variables (family history of GD and Ashkenazi‐Jewish ancestry) were identified. For type 3 disease, nine major signs (splenomegaly, oculomotor disturbances, thrombocytopenia, epilepsy, anaemia, hepatomegaly, bone pain, motor disturbances and kyphosis) and one major co‐variable (family history of GD) were identified. Lack of disease awareness, overlooking mild early signs and failure to consider GD as a diagnostic differential were considered major barriers to early diagnosis.ConclusionThe signs and co‐variables identified in the GED‐C initiative as potentially indicative of early GD will help to guide non‐specialists and raise their index of suspicion in identifying patients potentially suitable for diagnostic testing for GD.

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

“…It was specified a priori that indicators awarded an importance score of ≥3 by >75% of the panel would be tested for consensus in round 3, and that agreement on treatment recommendations would be reached if an agreement score of ≥4 was awarded by >67% of the panel. All ratings compiled by the administrator were reviewed by the cochairs as per the predefined scores and consistent with previous Delphi initiatives 20 21 ; agreement on treatment recommendations concluded in round 2. In round 3, panellists rated their level of agreement with each indicator that had met the designated importance criteria in round 2, using the 5-point Likert scale already described.…”

Rare GBA1 genotype associated with severe bone disease in Gaucher disease type 1

“…Mehta et al published in 2019 [26] the presenting signs and patient co-variables in Gaucher disease, and highlighted that physicians can fail to recognise the early stages of GD, which can lead to significant diagnostic delays and sometimes irreversible but avoidable morbidities. When it comes to a classic GD phenotype with massive splenomegaly, bone pain and cytopenias, diagnosis is more intuitive.…”

Scoring system to facilitate diagnosis of Gaucher disease

“…The GED-C initiative recruited 22 experts in GD, who used Delphi consensus methodology 8 to identify factors most likely to be indicative of type 1 GD. 9 Nine major factors were agreed (splenomegaly, thrombocytopenia, bone-related manifestations, anaemia, hyperferritinaemia, hepatomegaly, gammopathy, family history of GD, Ashkenazi Jewish ancestry), as well as 10 minor factors. 9 The subsequent aim of the GED-C initiative was to use these factors to create a simple scoring-based algorithm for use by non-specialist physicians or patients as an aid for the diagnosis of GD.…”

“…9 Nine major factors were agreed (splenomegaly, thrombocytopenia, bone-related manifestations, anaemia, hyperferritinaemia, hepatomegaly, gammopathy, family history of GD, Ashkenazi Jewish ancestry), as well as 10 minor factors. 9 The subsequent aim of the GED-C initiative was to use these factors to create a simple scoring-based algorithm for use by non-specialist physicians or patients as an aid for the diagnosis of GD. Scoring systems are an established aid in diagnosing several diseases, such as systemic lupus erythematosus.…”

“…10 The factors and a prototype point scoring system (PSS) generated by the GED-C panel are shown in Table 1. 9 Combining the weightings allocated to each factor in the prototype PSS allows an aggregate score to be calculated for each patient. The recommendation to test for GD would depend on whether this score exceeded a predetermined threshold value.…”