Natural History and Burden of Disease Among Patients With Juvenile GM2 Gangliosidoses in France
Author(s)
Daisy Ng-Mak, PhD1, Sarah Ba, MSc1, Samia Pichard, MD2, Laurence Watier, PhD3, Leila Alaoui Sosse, MSc4, Sarah Bakiri, MSc4, Camille Berenguier, PhD4, Patricia Viard, PhD4, Yann Nadjar, PhD5;
1Sanofi, Cambridge, MA, USA, 2Hôpital Necker Enfants Malades, Reference Center for Lysosomal Storage Diseases, Paris, France, 3Institut Pasteur, Université Paris-Cité, Epidemiology and Modelling of Antimicrobials Evasion (EMAE), Paris, France, 4Oracle Life Sciences, Paris, France, 5Pitié-Salpêtrière Hospital, Reference Center for Lysosomal and Metabolic Neurological Diseases, Paris, France
1Sanofi, Cambridge, MA, USA, 2Hôpital Necker Enfants Malades, Reference Center for Lysosomal Storage Diseases, Paris, France, 3Institut Pasteur, Université Paris-Cité, Epidemiology and Modelling of Antimicrobials Evasion (EMAE), Paris, France, 4Oracle Life Sciences, Paris, France, 5Pitié-Salpêtrière Hospital, Reference Center for Lysosomal and Metabolic Neurological Diseases, Paris, France
Presentation Documents
OBJECTIVES: GM2 gangliosidoses (Tay-Sachs disease [TSD], Sandhoff disease [SD], and GM2 activator protein [GM2AP]] deficiency) are rare, autosomal recessive, potentially life-threatening, disabling disorders characterized by progressive neurodegeneration, with no approved therapies. These are classified into infantile, juvenile, and late-onset forms based on patients’ age at symptom onset. This study aimed to address the evidence gap regarding the clinical burden and progression of juvenile GM2 gangliosidoses in France.
METHODS: This retrospective, non-interventional, longitudinal study estimated the burden of neurological and non-neurological manifestations on patients with juvenile GM2 gangliosidoses (aged 2-10 years at onset). Data on demographics, clinical manifestations, and disease impact were abstracted from medical charts (2009-2022) in France.
RESULTS: A total of 10 patients (TSD [n=7], SD [n=1], GM2AP [n=1] deficiency, and unknown [n=1]) were identified, with a median (interquartile range [IQR]) age of 7.5 (6.0-13.0) years at diagnosis; two patients were previously misdiagnosed, and five had abnormal neurodevelopment. All patients had at least one neurological (median [IQR] number of neurological manifestations/patient: 6.5 [4.0-9.0]) and non-neurological manifestation(s) (median [IQR]: 1.0 [1.0-2.0]), with two patients reporting ≥10 neurological manifestations. The most frequently reported neurological manifestations included gait disorder (n=10), dysarthria (n=9), and ataxia, behavior/psychiatric and cognitive disorder (n=6 each), whereas common non-neurological manifestations were fatigue (n=5), bladder disorder (n=4), and gastrointestinal dysfunction (n=3). Patients experienced disease-related impacts requiring mobility adaptations (n=8), including wheelchair use (n=5), personal hygiene assistance (n=7), caregiver support (n=6), and rehabilitation therapies (n=4), including physical (n=3) and speech (n=4) therapies. Four deaths related to GM2 gangliosidoses were reported, with a median (IQR) age of 13.0 (7.9-25.8) years at death.
CONCLUSIONS: The study highlights a substantial burden of illness, resulting in functional impairments and underscores the need of an effective disease-modifying treatment for patients with juvenile GM2 gangliosidoses in France.
METHODS: This retrospective, non-interventional, longitudinal study estimated the burden of neurological and non-neurological manifestations on patients with juvenile GM2 gangliosidoses (aged 2-10 years at onset). Data on demographics, clinical manifestations, and disease impact were abstracted from medical charts (2009-2022) in France.
RESULTS: A total of 10 patients (TSD [n=7], SD [n=1], GM2AP [n=1] deficiency, and unknown [n=1]) were identified, with a median (interquartile range [IQR]) age of 7.5 (6.0-13.0) years at diagnosis; two patients were previously misdiagnosed, and five had abnormal neurodevelopment. All patients had at least one neurological (median [IQR] number of neurological manifestations/patient: 6.5 [4.0-9.0]) and non-neurological manifestation(s) (median [IQR]: 1.0 [1.0-2.0]), with two patients reporting ≥10 neurological manifestations. The most frequently reported neurological manifestations included gait disorder (n=10), dysarthria (n=9), and ataxia, behavior/psychiatric and cognitive disorder (n=6 each), whereas common non-neurological manifestations were fatigue (n=5), bladder disorder (n=4), and gastrointestinal dysfunction (n=3). Patients experienced disease-related impacts requiring mobility adaptations (n=8), including wheelchair use (n=5), personal hygiene assistance (n=7), caregiver support (n=6), and rehabilitation therapies (n=4), including physical (n=3) and speech (n=4) therapies. Four deaths related to GM2 gangliosidoses were reported, with a median (IQR) age of 13.0 (7.9-25.8) years at death.
CONCLUSIONS: The study highlights a substantial burden of illness, resulting in functional impairments and underscores the need of an effective disease-modifying treatment for patients with juvenile GM2 gangliosidoses in France.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
EPH8
Topic
Epidemiology & Public Health
Topic Subcategory
Public Health
Disease
SDC: Neurological Disorders, SDC: Pediatrics, SDC: Rare & Orphan Diseases, STA: Genetic, Regenerative & Curative Therapies