FV 1182. Ataxia and/or Language Regression at Early School Age—Think of Atypical CLN2 Disease

Background: Neuronal ceroid lipofuscinosis type 2 (CLN2) is a lysosomal storage disorder caused by deficiency of tripeptidylpeptidase 1 (TPP1). The classic phenotype is late infantile with an early language developmental delay, first clear clinical signs at the ages of 3 to 4 years with seizures and a rapid decline of psychomotor functions. Most children are bedridden at 5 years and die around the age of 10 years. However, atypical phenotypes are reported in the literature which is likely to be diagnosed with significant delay. With the recent approval of intraventricular enzyme replacement therapy (ERT) with cerliponase α for CLN2 disease, early diagnosis has become key to initiate treatment before the disease has already progressed severely.

Objectives and Methods: To improve early diagnosis in patients with atypical phenotypes of CLN2 disease, we analyzed and followed a cohort of four patients with atypical juvenile phenotypes of CLN2 in our clinic.

Results: All four patients show an atypical juvenile phenotype.

Patient 1 started presenting symptoms at the age of 10 years with progressive ataxia and mild language regression. He never showed signs of epilepsy. He was diagnosed at the age of 11 years 5 months.

Patient 2 presented first symptoms at the age of 8 years 6 months with language regression followed by ataxia. Epilepsy developed at the age of 11 years and 4 months. She was diagnosed at the age of 9 years and 6 months.

Patient 3 developed first symptoms at the age of 6 years 4 months, with progressive ataxia, followed by language regression at the age of 8 years 6 months and first seizures at the age of 10 years 6 months. By the age of 11 years 6 months only aided walking was possible. She was diagnosed at the age of 11 years 11 months.

Patient 4 showed an onset of symptoms at the age of 5 years with ataxia and language deterioration. First seizures developed at the age of 6 years 3 months. At the age of 9 years 1 month, he was not able to walk independently any more. The diagnosis was confirmed at the age of 8 years 4 months.

All patients started ERT between the ages of 9 years 1 month and 12 years 9 months and are still under treatment.

Conclusion: In our cohort, we present patients with CLN2 disease that do not show the characteristic age of onset and clinical course of disease. All four patients presented at the age of 5 years or later with ataxia quickly followed by a language deterioration. Epilepsy developed later between 6 and 10 years, or never. Since there is a new treatment for CLN2 available, it is important to diagnose this disease as early as possible to avoid progression and possible additional onset of symptoms of the disease. Our experiences emphasize the importance of early testing for this disease whenever there is a motor or language regression in the childhood or adolescence even if the epilepsy is not present.