Natural History of Adult Patients with GM2 Gangliosidosis.
Action Potentials
Adolescent
Adult
Age of Onset
Aged
Atrophy
Brain
/ diagnostic imaging
Cerebellum
/ diagnostic imaging
Child
Cognitive Dysfunction
/ physiopathology
Cohort Studies
Deglutition Disorders
/ physiopathology
Disease Progression
Dysarthria
/ physiopathology
Dystonia
/ physiopathology
Electrodiagnosis
Electromyography
Female
Gait Ataxia
/ physiopathology
Gangliosidoses, GM2
/ diagnostic imaging
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Motor Neuron Disease
/ physiopathology
Muscle Spasticity
/ physiopathology
Muscle Weakness
/ physiopathology
Neural Conduction
Sandhoff Disease
/ diagnostic imaging
Tay-Sachs Disease
/ diagnostic imaging
Young Adult
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
24
05
2019
revised:
23
01
2020
accepted:
23
01
2020
pubmed:
30
1
2020
medline:
28
7
2020
entrez:
30
1
2020
Statut:
ppublish
Résumé
GM2 gangliosidoses are lysosomal diseases due to biallelic mutations in the HEXA (Tay-Sachs disease [TS]) or HEXB (Sandhoff disease [SD]) genes, with subsequent low hexosaminidase(s) activity. Most patients have childhood onset, but some experience the first symptoms during adolescence/adulthood. This study aims to clarify the natural history of adult patients with GM2 gangliosidosis. We retrospectively described 12 patients from a French cohort and 45 patients from the literature. We observed 4 typical presentations: (1) lower motoneuron disorder responsible for proximal lower limb weakness that subsequently expanded to the upper limbs, (2) cerebellar ataxia, (3) psychosis and/or severe mood disorder (only in the TS patients), and (4) a complex phenotype mixing the above 3 manifestations. The psoas was the first and most affected muscle in the lower limbs, whereas the triceps and interosseous were predominantly involved in the upper limbs. A longitudinal study of compound motor action potentials showed a progressive decrease in all nerves, with different kinetics. Sensory potentials were sometimes abnormally low, mainly in the SD patients. The main brain magnetic resonance imaging feature was cerebellar atrophy, even in patients without cerebellar symptoms. The prognosis was mainly related to gait disorder, as we showed that beyond 20 years of disease evolution, half of the patients were wheelchair users. Improved knowledge of GM2 gangliosidosis in adults will help clinicians achieve correct diagnoses and better inform patients on the evolution and prognosis. It may also contribute to defining proper outcome measures when testing emerging therapies. ANN NEUROL 2020;87:609-617.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
609-617Informations de copyright
© 2020 American Neurological Association.
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