Neuronal ceroid lipofuscinosis type 5 in Russia: first case report and literature review

Abstract

Neuronal ceroid lipofuscinosis (NCL) is one of the most common causes of childhood dementia. NCL type 5 is characterized by epileptic seizures, cognitive decline, and progressive vision loss. Whole exome sequencing was performed, and the identified variant was confirmed by Sanger sequencing. Despite various therapeutic regimens, including novel approaches, seizure control could not be achieved. The disease was caused by a previously undescribed pathogenic variant CLN5(NM_006493.4):c.368del (p.Arg123LysfsTer4). This is the first known case of NCL type 5 in Russia. Unusually, the patient also had a cervical lymphangioma requiring separate medical and surgical intervention. This case report contributes to our understanding of the natural history of CLN5-associated NCL and may support the development of gene therapy approaches for its treatment.

Keywords: CLN5; epilepsy; neurodegenerative disease; neuronal ceroid lipofuscinosis; next-generation sequencing.

Figure 1

(A) Axial T2-weighted slice demonstrates excessive widening of cerebellar sulci and expansion of cisternal spaces in the posterior cranial fossa, reflecting moderate cerebellar atrophic volume loss. (B) Axial T2 FLAIR slice reveals mild periventricular leukoencephalopathy in the white matter of the frontal and parietal lobes. (C) Sagittal T1-weighted slice shows reduced cerebellar volume with an enlarged posterior cranial fossa, clearly illustrating cerebellar atrophy.

Figure 2

Magnetic resonance imaging of the patient’s brain performed in 7 years 6 months ago.

Figure 3

(A) Electroencephalography (EEG) during wakefulness (age 7 years and 6 months). Parameters: speed = 30 mm/s, sensitivity = 10 μV/mm, high-frequency filter = 0.5 Hz, low-frequency filter = 70 Hz, notch filter = 50 Hz, bipolar longitudinal montage. (B) EEG during daytime sleep (age 7 years and 6 months). Parameters: speed = 30 mm/s, sensitivity = 10 μV/mm, low-frequency filter (LFF) = 0.5 Hz, high-frequency filter (HFF) = 70 Hz, notch filter = 50 Hz, bipolar longitudinal montage.

Figure 4

(A) Sanger sequencing results in the nuclear family, (B) Pedigree of the proband, (C) Distribution of variants in the CLN5 gene by type, dup – duplication.