Neuronal ceroid lipofuscinosis: when to use right clues for a rare disease?

Case presentation: We describe the case of a previously healthy girl who, at 6 years of age, initiates a difficult-to-control epilepsy associated with agitation and aggressiveness. At the age of 9, she already showed school difficulties, infantilization, dependence for daily activities and signs of dementia. The neuroimaging that was initially normal at the age of 11 showed cerebellar atrophy and small frontal to left subcortical focus with lateral ventricle asymmetry. EEG showed sharp waves and complex acute occipital tips on the right and slow and wide waves. Genetic panel of epilepsy and ataxia showed two variants in heterozygosis in the MFSD8 gene diagnosing neuronal ceroid lipofuscinosis 7.

Discussion: The lipofuscinoses are a group of inherited neurodegenerative lysosomal storage diseases characterized by intracellular accumulation of autofluorescent lipopigment. Collectively they are the most common cause of genetic neurodegenerative disease of childhood with an estimated incidence of 1.3 to 7/100,000 live births. LCN7 is a late onset variant of childhood, typically between two to seven years of age, with severe epilepsy and aggressive behavior, associated with developmental regression. It progresses rapidly with onset of myoclonus, ataxia, dementia, and blindness. It occurs by mutation in the MFSD8 gene that encodes a lysosomal transmembrane protein. Brain MRI shows cerebral and cerebellar atrophy with signal hyperintensity in the white matter. EEG usually shows slow baseline activity and multifocal, occipital epileptiform discharges. Ophthalmologic examination may reveal retinopathy and optic atrophy. Currently genetic testing is the diagnostic method of choice through epilepsy gene panel or exome sequencing.

Final comments: Treatment in this subtype is supportive only with a reserved prognosis. However, it is important to research LCN in the context of children with behavioral regression, refractory epilepsy, visual loss and progressive ataxia with cerebellar atrophy since we have a disease-modifying therapy in the LCN 2 subtype through enzyme replacement with intrathecal application of recombinant human cerliponase alfa in those older than three years.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
18 September 2023