[en] Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare, lysosomal storage disorder that causes pediatric onset neurodegenerative disease. It is characterized by mutations in the TPP1 gene. Symptoms begin between 2 and 4 years of age with loss of previously acquired motor, cognitive, and language abilities. Cerliponase alfa, a recombinant human TPP1 enzyme, is the only approved therapy. We report the first presymptomatic cerliponase alfa intraventricular treatment in a familial case of CLN2 related to a classical TPP1 variant. Sister 1 presented with motor, cognitive, and language decline and progressive myoclonic epilepsy since the age of 3 years, evolved with severe diffuse encephalopathy, received no specific treatment, and died at 11 years. Sister 2 had a CLN2 presymptomatic diagnosis and has been treated with cerliponase since she was 12 months old. She is now 6 years 8 months and has no CLN2 symptom except one generalized seizure 1 year ago. No serious adverse event has occurred. Repeated Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition standardized index scores are heterogeneous in the extremely low to low average ranges. Mean length of utterances, a global index of sentence complexity, showed a delay, but a gradual improvement. The reported case enhances the major contribution of presymptomatic diagnosis and significant middle-term treatment benefit for patients with CLN2.
Disciplines :
Neurology
Author, co-author :
Breuillard, Delphine; Pediatric Neurology Department, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Université de Paris Cité, Paris, France.
Ouss, Lisa ; Université de Liège - ULiège > Département des sciences cliniques > Psychiatrie infanto-juvénile ; Child Psychiatry Department, Necker-Enfants Malades Hospital, AP-HP, Université de Paris Cité, Paris, France.
Le Normand, Marie Thérèse; Pasteur Institute, Audition Institute, Inserm, Paris, France. ; Psychopathology Laboratory, URP4057, Université de Paris Cité, Boulogne-Billancourt, France.
Denis, Timothée de Saint; Pediatric Neurosurgery Department Necker-Enfants Malades Hospital, AP-HP, Université de Paris Cité, Paris, France.
Barnerias, Christine; Pediatric Neurology Department, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Université de Paris Cité, Paris, France.
Robert, Matthieu P; Ophthalmology Department, Necker-Enfants Malades Hospital, AP-HP, Université de Paris Cité, Paris, France.
Eisermann, Monika; Clinical Neurophysiology, Hôpital Necker Enfants Malades, AP-HP, Paris Université, Paris, France.
Boddaert, Nathalie; Pediatric Radiology Department, Necker-Enfants Malades Hospital, AP-HP, Université de Paris Cité, Paris, France.
Caillaud, Catherine; Metabolic Biochemistry Department, Necker-Enfants Malades Hospital, AP-HP, Université de Paris Cité, Paris, France. ; Inserm U1151, CNRS UMR8253, Necker-Enfants Malades Institute, Université de Paris Cité, Paris, France.
Bahi-Buisson, Nadia; Pediatric Neurology Department, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Université de Paris Cité, Paris, France.
Desguerre, Isabelle; Pediatric Neurology Department, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Université de Paris Cité, Paris, France.
Aubart, Mélodie ; Pediatric Neurology Department, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Université de Paris Cité, Paris, France.
Language :
English
Title :
Ceroid lipofuscinosis type 2 disease: Effective presymptomatic therapy-Oldest case of a presymptomatic enzyme therapy.
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