A Novel Variant of the CTSD Gene Associated with Juvenile-onset Neuronal Ceroid Lipofuscinosis Type 10: A Case Report and Literature Review

Abstract

Neuronal ceroid lipofuscinosis type 10 (NCL10) is a rare progressive neurodegenerative disease associated with homozygous or compound heterozygous mutations in the CTSD gene encoding cathepsin D protein. It is classified as congenital, infantile, or juvenile NCL10 according to the age at onset of symptoms. Six cases of juvenile onset NCL10 (JNCL10) have been reported thus far in the literature. Herein, we report a nine-year-six-month-old girl with speech disorders, cognitive and motor decline, ataxia, and visual impairment. Developmental milestones were reported to be normal up to the age of 7 years. Biochemical and metabolic studies were normal. Electroencephalography showed intermittent generalized high-amplitude delta-wave activity during light sleep. Brain magnetic resonance imaging showed mild cerebellar atrophy. Whole-exome sequencing (WES) revealed a novel homozygous missense variant of c.1097G > A (p. Cys366Tyr) in the CTSD gene. Based on clinical, laboratory, and genetic findings, the patient was diagnosed with JNCL10. To the best of our knowledge, this is a novel variant and the first case reported in Turkey, and it is important in terms of broadening ethnicity and the spectrum of EEG findings.

Keywords: CTSD; Cathepsin D deficiency; Juvenile; Neuronal ceroid lipofuscinosis type 10; Novel variant.