Natural History of Adult Patients with GM2 Gangliosidosis.

Abstract

OBJECTIVE:

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.

METHODS:

We retrospectively described 12 patients from a French cohort and 45 patients from the literature.

RESULTS:

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.

INTERPRETATION:

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.

• Authors: Marion Masingue, Louis Dufour, Timothée Lenglet, Lisa Saleille, Cyril Goizet, Xavier Ayrignac, Fabienne Ory-Magne, Magali Barth, Foudil Lamari, Daniele Mandia, Catherine Caillaud, Yann Nadjar
• Journal: Annals of neurology (Ann Neurol) Vol. 87 Issue 4 Pg. 609-617 (04 2020) ISSN: 1531-8249 [Electronic] United States
• PMID: 31995250 (Publication Type: Journal Article)
• Copyright: © 2020 American Neurological Association.

Topics

• Action Potentials
• Adolescent
• Adult
• Age of Onset
• Aged
• Atrophy
• Brain (diagnostic imaging, pathology)
• Cerebellum (diagnostic imaging, pathology)
• Child
• Cognitive Dysfunction (physiopathology, psychology)
• Cohort Studies
• Deglutition Disorders (physiopathology)
• Disease Progression
• Dysarthria (physiopathology)
• Dystonia (physiopathology)
• Electrodiagnosis
• Electromyography
• Female
• Gait Ataxia (physiopathology)
• Gangliosidoses, GM2 (diagnostic imaging, physiopathology, psychology)
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Motor Neuron Disease (physiopathology)
• Muscle Spasticity (physiopathology)
• Muscle Weakness (physiopathology)
• Neural Conduction
• Sandhoff Disease (diagnostic imaging, physiopathology, psychology)
• Tay-Sachs Disease (diagnostic imaging, physiopathology, psychology)
• Young Adult