First Reported Case of CLN5 Disease in Japan: Identification of a Novel Homozygous Pathogenic Variant Through Whole...

Neuronal ceroid lipofuscinoses (NCL) belong to a group of inherited neurodegenerative diseases characterized by psychomotor regression, seizures, and visual impairment, resulting from intracellular accumulation of lipofuscin. CLN5, a subtype typically manifesting between ages 4 to 17, is particularly rare in non-Finnish populations. Here, we report the first Japanese case of CLN5 in a 12-year-old girl with progressive myoclonic epilepsy and psychomotor regression. Initial assessments for common metabolic disorders, including GM2 gangliosidosis, were inconclusive. Trio-based genome sequencing (GS) identified a novel homozygous pathogenic variant in CLN5, confirming the diagnosis at 10 years and 6 months of age. Subsequent evaluations revealed progressive cerebral and cerebellar atrophy and vision loss. This case underscores the importance of GS in diagnosing rare neurodegenerative diseases and highlights the clinical spectrum of CLN5, which presents with rapid neurological decline. Expanding diagnostic frameworks with genetic testing is critical for early diagnosis and potential therapeutic interventions in CLN5 and related NCL disorders.