The neuronal ceroid lipofuscinoses (NCLs) are genetic disorders characterised by accumulation of autofluorescent material resembling lipofuscin or ceroid. Most patients present with cognitive and motor decline, seizures and visual loss. NCLs are the most prevalent neurodegenerative disorders of childhood. CLN5 encodes ceroid lipofuscinosis neuronal protein 5, which has three major putative functions: trafficking lysosomal sorting receptors, lysosomal and non-lysosomal palmitoyl thioesterase activity.1

CLN5 variants were described mainly in Caucasians, but patients from several populations were already reported. Here, we describe 17 South American patients harbouring ten CLN5 pathogenic variants, including five novel variants, one with a founder effect. This case series broadens the phenotype of CLN5 by describing an unusual adult-onset patient.

Patients were identified through a search for pathogenic variants in the CLN5 gene in the database of a commercial laboratory and by contacting centres for neurogenetic diseases in South America. Genetic analysis was performed using next-generation sequencing through whole-exome sequencing (WES) or epilepsy gene panels. Variants were classified according to American College of Medical Genetics (ACMG) guidelines. Haplotype analysis was performed in four phased-VCFs (variant call format) using a custom script.

We identified 19 patients from 17 families. Two were excluded because of insufficient clinical data. Table 1 shows a summary of clinical details and genetic profiles.

Clinical and genetic features of CLN5 patients in South America

We analysed 17 patients from 16 families with age of onset varying between 1 and 40 years, 5 males and 12 females. All patients presented with cognitive and motor decline, ataxia and seizures. Most patients (14/17) had visual impairment. All patients had behaviour abnormalities ranging from anxiety and inattention to stereotypic behaviour, in most cases initiated in the first years of disease. Seizures were the presenting feature in nine patients and language disorders in other six.

Cerebellar, cortical and subcortical …