Dataset Information

Scoring system to facilitate diagnosis of Gaucher disease.

ABSTRACT:

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.

SUBMITTER: Mehta A

PROVIDER: S-EPMC7839708 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Scoring system to facilitate diagnosis of Gaucher disease.

Mehta Atul A Rivero-Arias Oliver O Abdelwahab Magy M Campbell Samantha S McMillan Annabel A Rolfe Mark J MJ Bright Jeremy R JR Kuter David J DJ

Internal medicine journal 20201201 12

<h4>Background</h4>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.<h4>Aims</h4>To validate the PSS retrospectively in a test population including patients with GD and other conditions with ...[more]

PMID: 33174353

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Project description:BackgroundGD1-DS3 is an integrated assessment of type 1 Gaucher disease (GD1) burden based on bone, hematologic and visceral domains. We investigated this disease severity scoring system (DS3) methodology for initial assessment, long-term follow-up and evaluation of treatment responses.MethodsWe enrolled 133 treated adult GD1 patients. Baseline DS3 scores were calculated near the initial treatment date and patients stratified by severity as marked (DS3 6.00-19.00), moderate (DS3 3.00-5.99), mild (DS3 < 3.00). Follow-up scores were calculated annually. Minimal clinically important improvement (MCII), is defined as ΔDS3 of -3.1.ResultsPatient characteristicsN370S was the most common allele (118 patients had at least one), 52 were N370S/N370S (48/52 were Ashkenazi Jews), N370S/L444P was the most common genotype among non-Jews. Median age of treatment: 45 years; median follow-up: 14 years. Baseline DS3 scores: Patients with marked disease (N = 58; median 7.84) were least likely to be N370S homozygous (19 %) and most likely to have had splenectomy (53 %), early age at diagnosis (median 18 years) and major pre-treatment bone pathology (76 %). Among patients with moderate disease (N = 53; median 4.33), 49 % were N370S/N370S, 15.1 % had splenectomy and 17 % had major bone disease. Median age at diagnosis: 32 years. No patient with mild disease (N = 22; median 2.4) had splenectomy or major skeletal disease. Median age at diagnosis: 40 years. 68 % were N370S homozygous. Response to treatment: Health-state transitions occurred primarily during the early treatment years. At Year 5, among 48 evaluable patients with marked baseline disease, eight were unchanged in severity status whereas 40 had MCII of varying degrees with 11 scored as mild. Among 42 evaluable moderate patients, none worsened, 16 remained moderate and 26 improved to mild. Among 16 evaluable mild patients, 14 remained so and 2 had DS3 scores in the low moderate range.ConclusionsDS3 is effective for assessing disease burden in GD1 and for monitoring response. ERT was associated with MCII in DS3 scores in patients with high severity. Nevertheless, despite better DS3 scores with treatment, GD1 patients especially those with splenectomy and pre-treatment bone pathology, continued to have bone complications.

Project description:BackgroundGaucher disease (GD) is a rare inherited multiorgan disorder, yet a diagnosis can be significantly delayed due to a broad spectrum of symptoms and lack of disease awareness. Recently, the prototype of a GD point-scoring system (PSS) was established by the Gaucher Earlier Diagnosis Consensus (GED-C) initiative, and more recently, validated in Gaucher patients in UK. In our study, the original GED-C PSS was tested in Finnish GD patients. Furthermore, the feasibility of point scoring large electronic health record (EHR) data set by data mining to identify potential undiagnosed GD cases was evaluated.MethodsThis biobank study was conducted in collaboration with two Finnish biobanks. Five previously diagnosed Finnish GD patients and ~ 170,000 adult biobank subjects were included in the study. The original PSS was locally adjusted due to data availability issues and applied to the Finnish EHR data representing special health care recordings.ResultsAll GD patients had high levels of the biomarker lyso-Gb1 and deleterious GBA mutations. One patient was a compound heterozygote with a novel variant, potentially pathogenic mutation. Finnish EHR data allowed the retrospective assessment of 27-30 of the 32 original GED-C signs/co-variables. Total point scores of GD patients were high but variable, 6-18.5 points per patient (based on the available data on 28-29 signs/co-variables per patient). All GD patients had been recorded with anaemia while only three patients had a record of splenomegaly. 0.72% of biobank subjects were assigned at least 6 points but none of these potential "GD suspects" had a point score as high as 18.5. Splenomegaly had been recorded for 0.25% of biobank subjects and was associated with variable point score distribution and co-occurring ICD-10 diagnoses.DiscussionThis study provides an indicative GED-C PSS score range for confirmed GD patients, also representing potential mild cases, and demonstrates the feasibility of scoring Finnish EHR data by data mining in order to screen for undiagnosed GD patients. Further prioritisation of the "GD suspects" with more developed algorithms and data-mining approaches is needed.FundingThis study was funded by Shire (now part of Takeda).

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Dataset Information

Scoring system to facilitate diagnosis of Gaucher disease.

Background

Aims

Methods

Results

Conclusions

Publications

Scoring system to facilitate diagnosis of Gaucher disease.

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