To create a system to categorize confidence in the diagnosis of CLN3 disease.

We created 4 diagnostic confidence levels: 1 - Genetically Confirmed (mutation in CLN3 on each allele), 2 - Clinically Probable (CLN3 mutation on one allele and additional diagnostic evidence, such as electron microscopy), 3 - Clinically Possible (no genetic testing results but with other diagnostic evidence), 4 - Clinical CLN3 disease with an additional cause for neurodevelopmental disability. Levels 1 and 2 were divided into 4 subcategories based on the clinical disease course (A - classic Juvenile Neuronal Ceroid Lipofuscinoses, B - vision loss only past age 12 years, C - vision loss only or pre-symptomatic < 12 years, D - atypical phenotype). Level 4 was divided into 2 subcategories based on etiology of the secondary diagnosis. Clinical course was defined by age-at-onset, disease severity, or a combination. Individuals with atypical phenotypes were discussed as a team until consensus was reached.

A total of 136 individuals were evaluated and classified into category 1 (N=103), category 2 (N=21), category 3 (N=7), and category 4 (N=5). Two individuals with complex genotypes required discussion regarding placement, but consensus was reached and all evaluated individuals were able to be classified.

This diagnostic confidence system has high face validity, is easy to apply, and has relevance for developing inclusion/exclusion criteria for use in trials or for weighting data based on confidence.