Cerliponase Alfa Treatment in a Pre-Symptomatic Patient with Neuronal Ceroid Lipofuscinosis Type 2 CLN2 and Atypical Phenotype: A Case Report

Ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disease, the most frequent variant of the NCL spectrum in South America. Since 2017, cerliponase alfa enzyme replacement therapy has been available in Colombia, leading to a reduction in the progression of neurological symptoms. However, little is known about its benefit in pre-symptomatic patients, even less in atypical phenotype, which to our knowledge has not been reported before.

The evolution over four years (2018 - 23) of two siblings diagnosed with CLN2, with atypical phenotype, compound heterozygous for: c.622C>T p.(Arg208*); c.887-10AG. One symptomatic boy (10 y) and one other pre-symptomatic girl (3 y) was evaluated using clinical scales (EEG, MRI). The older sibling was diagnosed after the onset of epilepsy at 6 years, however, he had language regression from 4 years, progressive dementia and ataxia. The youngest has been asymptomatic. They were both treated with intracerebroventricular cerliponase alfa, with adequate adherence, with only mild episodic pleocytosis in the boy and no adverse effects in the girl. Among the most important aspects, the functional scales (CLN2 clinical rating scale; Hamburg) stand out. There was no deterioration in the symptomatic patient, with a CLN score of 4/6 and Hamburg scale of 9/12 and no changes in follow-up: seizure free on levetiracetam, MRI with stable cerebellar atrophy, EEG with mild encephalopathy, and occasional epileptic activity which is now controlled. In the presymptomatic patient, no deterioration was recorded throughout the follow-up, with a CLN score of 6/6 and Hamburg score of 12/12. No MRI atrophy, and a normal EEG. The girl at this time is schooled with adequate performance, and no language regression.

Conclusion: In this case, the use of cerliponase alfa enzyme replacement therapy delays the progression of symptoms, and is safe and effective in symptomatic and pre-symptomatic patients. A high suspicion index is necessary as the atypical phenotype is not suspected early in most cases, so may go undiagnosed for a long time. When diagnosed, the study of siblings is recommended. In this family, the girl is asymptomatic with no language symptoms well past the age at which symptoms have started in her brother which highlights the potential benefits of this therapy in this particular population.