Clinical and molecular characteristics of neuronal ceroid lipofuscinosis in Saudi Arabia

BACKGROUND Neuronal ceroid lipofuscinoses (NCLs) represent a heterogeneous group of inherited metabolic lysosomal disorders characterized by neurodegeneration. This study sought to describe the clinical and molecular characteristics of NCLs in Saudi Arabia and determine the most common types in that population. METHODS A retrospective review of electronic medical records was conducted for 63 NCL patients (55 families) from six tertiary and referral centers in Saudi Arabia between 2008 to 2022. Clinical, radiological, and neurophysiological data as well as genetic diagnoses were reviewed. RESULTS CLN6 was the predominant type, accounting for 45% of cases in 25 families. The most common initial symptoms were speech delay (53%), cognitive decline (50%) and/or gait abnormalities (48%), and seizure (40%). Behavioral symptomatology was observed in 20% while visual impairment was less frequently (9.3%) encountered. Diffuse cerebral and cerebellar atrophy was the predominant finding on brain MRI. Electroencephalography generally revealed background slowing in all patients with generalized epileptiform discharges in 60%. The most common genotype detected was the p.Ser265del variant found in 36% (20/55 families). The most rapidly progressive subtypes were CLN2 and CLN6. Two patients with each died at 5 years of age. The earliest age at which a patient was non-ambulatory was 2 years in a patient with CLN14. CONCLUSIONS This is the largest molecularly confirmed NCL cohort study from Saudi Arabia. Characterizing the natural history of specific NLC types can increase understanding of the underlying pathophysiology and distinctive genotype-phenotype characteristics, facilitating early diagnosis and treatment initiation as well as genetic counselling for families.