Bastien Estublier1, Aline Cano2, Célia Hoebeke2, Samia Pichard3, Didier Scavarda4, Isabelle Desguerre5, Stéphane Auvin3, Brigitte Chabrol2. 1. Service of Paediatric Neurology, University Hospital of Toulouse, Hôpital des Enfants, 330 Avenue de Grande Bretagne, 31300, Toulouse, France. Electronic address: estublier.b@chu-toulouse.fr. 2. Service of Paediatric Neurology, Centre for Inherited Metabolic Diseases, University Hospital of Marseille, Hôpital Timone Enfants, 278 Rue Saint-Pierre, 13005, Marseille, France. 3. Service of Paediatric Neurology, Centre for Inherited Metabolic Diseases, Hôpital Robert Debré, Boulevard Sérurier, 75019, Paris, France. 4. Service of Paediatric Neurosurgery, University Hospital of Marseille, Hôpital Timone Enfants, 278 Rue Saint-Pierre, 13005, Marseille, France. 5. Service of Paediatric Neurology, Hôpital Necker-Enfants Malades, 149 Rue de Sèvres, 75015, Paris, France.
Abstract
INTRODUCTION: Neuronal Ceroid Lipofuscinosis type 2 (CLN2) is a neurodegenerative lysosomal disease which leads to early dementia and death without treatment. The recently available therapy consists of intracerebroventricular enzyme substitution: cerliponase alfa. In this report, we describe the evolution of the first French children treated with cerliponase alfa. METHOD: CLN2 Clinical Rating Scale Motor-Language (CLN2 ML) assesses the motor and language evolution of CLN2 patients. We retrospectively studied patients' medical records: clinical symptoms, MRI conclusions, gene mutation, side effects of infusions, patient's age and CLN2 ML scores at diagnosis, at the beginning of enzyme replacement therapy (ERT) and at the last evaluation. Seven patients were included. RESULTS: Average age at diagnosis was 50 months ( ±10) with CLN2 ML score equal to 3.6 [1.5-5]. Average age at the beginning of ERT was 56 months ( ±13) with CLN2 ML score equal to 3.1 [1-5]. At the last available evaluation, average age was 82 months ( ±20) with CLN2 ML score equal to 2.8 [0-5]. Thus, in 26 months, the mean CLN2 ML score only decreased by 0.3 points. However, patients with a CLN2 ML score greater than three at the onset of ERT experienced a stabilisation or improvement of clinical signs, whereas patients with a CLN2 ML score less than three at baseline continue to deteriorate. CONCLUSION: For patients starting ERT at an early stage of the disease, cerliponase alfa changes the natural history of the disease with a halt in disease progression or even a slight improvement in clinical symptoms.
INTRODUCTION:Neuronal Ceroid Lipofuscinosis type 2 (CLN2) is a neurodegenerative lysosomal disease which leads to early dementia and death without treatment. The recently available therapy consists of intracerebroventricular enzyme substitution: cerliponase alfa. In this report, we describe the evolution of the first French children treated with cerliponase alfa. METHOD:CLN2 Clinical Rating Scale Motor-Language (CLN2 ML) assesses the motor and language evolution of CLN2patients. We retrospectively studied patients' medical records: clinical symptoms, MRI conclusions, gene mutation, side effects of infusions, patient's age and CLN2 ML scores at diagnosis, at the beginning of enzyme replacement therapy (ERT) and at the last evaluation. Seven patients were included. RESULTS: Average age at diagnosis was 50 months ( ±10) with CLN2 ML score equal to 3.6 [1.5-5]. Average age at the beginning of ERT was 56 months ( ±13) with CLN2 ML score equal to 3.1 [1-5]. At the last available evaluation, average age was 82 months ( ±20) with CLN2 ML score equal to 2.8 [0-5]. Thus, in 26 months, the mean CLN2 ML score only decreased by 0.3 points. However, patients with a CLN2 ML score greater than three at the onset of ERT experienced a stabilisation or improvement of clinical signs, whereas patients with a CLN2 ML score less than three at baseline continue to deteriorate. CONCLUSION: For patients starting ERT at an early stage of the disease, cerliponase alfa changes the natural history of the disease with a halt in disease progression or even a slight improvement in clinical symptoms.
Authors: J Schaefers; L J van der Giessen; C Klees; E H Jacobs; S Sieverdink; M H G Dremmen; J K H Spoor; A T van der Ploeg; J M P van den Hout; H H Huidekoper Journal: Orphanet J Rare Dis Date: 2021-05-14 Impact factor: 4.123