510 Ultrastructural and Molecular Correlation in a Pediatric Case of CLN6-Associated Neuronal Ceroid Lipofuscinoses (NCLs)

Introduction/Objective Neuronal ceroid lipofuscinoses (NCLs), also known as Batten disease, represents a spectrum of inherited neurodegenerative disorders characterized by lysosomal accumulation of cellular ceroid lipofuscin, a waste product of lipids and proteins. CLN6-associated late-infantile NCL typically progress from developmental delays to regression, cognitive decline, and ultimately seizures. Diagnosis can be challenging due to the variable age of onset and clinical overlap with other neurodevelopmental disorders. We report a 4-year-old female presenting with early speech regression, behavioral concerns, and a prior autism diagnosis. Genetic testing identified a pathogenic CLN6 variant (c.406C>T, p.Arg136Cys) and a variant of uncertain significance (c.497T>C, p.Phe166Ser) on trans alleles. Ultrastructural examination of a skin punch biopsy revealed lipopigment inclusions with characteristic rectilinear complex, occasional fingerprint profiles, and rare curvilinear profiles in different skin cell types, morphologically diagnostic of NCL. Methods/Case Report Case Report Results NA Conclusion Electron microscopy of skin biopsy plays a critical role in confirming the diagnosis of CLN6-related NCL, particularly in genetically complex cases. The identification of different autolysosome inclusions, including rectilinear complex, fingerprint profiles, and curvilinear profiles provides pathologic confirmation of disease in the setting of equivocal clinical and genetic findings.