Table 1.

A summary table of the features of the diagnostic delay literature in genetic disease

Characteristics of the Diagnostic Delay Literature	Findings (N)
Top 10 genetic diseases investigated	Hereditary angioedema 26
Full list in the Supplemental Table 1 for other diseases	Familial Mediterranean fever 16 Inborn errors of immunity 12 Genetic autoinflammatory diseases 11 Alpha-1 antitrypsin deficiency 9 Pompe disease 8 Fabry disease 8 Duchenne muscular dystrophy 7 Severe Combined Immunodeficiency 6 Wilson disease 6
Number of patients in the studies	3-18182 (range) 446 (mean) 68.5 (median)
Top 10 countries investigated in diagnostic delay literature.	Multinational 46 Turkey 21
Full list in the Supplemental Table 1	USA 21 Iran 15 UK 13 China 13 Italy 13 France 11 Spain 9 Germany 9
Economic development status of the countries as per OECD data	Multinational 46 Developed 132 Developing 81 Least economically developed 0
Study settings	Singel academic medical center 124 National registry 41 Multiple academic medical centers 37 International registry 18 Literature 14 Patient support group 9 National lab 4 Commercial Study 3 Newborn screening network 2 Billing data 2 Drug outcome survey 1 Not specified 1 National network 1 Diagnostic lab 1 National biobank 1
Diagnostic delay ascertainment method	Retrospective chart review 135 Patient questionnaire 35 Clinical assessment 28 Physician questionnaire 19 Literature 13 Retrospective chart review plus questionnaire 8 Not mentioned 5 EMR records 2 Patient and physician survey 2 Retrospective chart review + literature 2 Billing data 2 Clinical assessment and chart review 2 Biobank data 1 Multiple registries 1 Literature and clinical assessment 1 Patient assessment and interview 1 Prospective data collection 1 Patient questionnaire and assessment 1
Diagnostic criteria	Billed data 2 Biochemical 13 Biochemical and clinical 2 Biochemical and genetic 40 Clinical 46 Clinical, biochemical, and genetic 2 Clinical and genetic 10 Clinical or genetic 2 Demographic 12 Demographic and genetic 1 Genetic 41 Literature 3 Not reported 66 Self-diagnosed 3 Society criteria 12 Treated patients 4
Diagnostic delay definition	Symptom onset to diagnosis 226 Self-reported 8 Presentation to diagnosis 6 Birth to dx 4 Referral to diagnosis 4 Not reported 4 Literature 2 Billing event to diagnosis 1 Suspicion to diagnosis 1 Symptom onset to differential diagnosis 1 Disease related visit to diagnosis 1 Newborn screen date to diagnosis 1
Statistics to report diagnostic day	Median 114 Mean 102 Mean and Median 15 Not reported 9 Range 10 Average 9
Studies that reported disease specific diagnostic delay value	203
Studies that reported disease specific diagnostic delay as a range	7
Studies that report stratified sub analysis by characteristics of disease (eg, phenotype or genotype).	49
Studies that measured diagnostic delay over time	37
Studies that reported that diagnostic delay improved with time	25
Studies that tested an intervention	5
Studies suggested intervention. Improved diagnostic delay	2
Interventions suggested	NONE 139 Awareness 44 NBS 23 Systems changes to clinical practice 19 More research 14 More genetic testing 10 Test family members 3 Multiple 3 Improved biochemical diagnosis 2 Algorithms 1 Study delay more as a concept 1