Natural History of Adult Patients with GM2 Gangliosidosis.
Ann Neurol. 2020-02-07; 87(4): 609-617
DOI: 10.1002/ana.25689
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1. Ann Neurol. 2020 Apr;87(4):609-617. doi: 10.1002/ana.25689. Epub 2020 Feb 7.
Natural History of Adult Patients with GM2 Gangliosidosis.
Masingue M(1), Dufour L(2), Lenglet T(3)(4), Saleille L(2), Goizet C(5)(6),
Ayrignac X(7), Ory-Magne F(8), Barth M(9), Lamari F(10), Mandia D(2), Caillaud
C(11)(12), Nadjar Y(2).
Author information:
(1)Reference Center for Neuromuscular Disorders Nord/Est/Île-de-France, Institute
of Myology, Pitié-Salpêtrière University Hospital Group (Assistance publique
Hôpitaux de Paris (AP-HP)), Paris.
(2)Department of Neurology, Reference Center for Lysosomal Diseases,
Neuro-Genetic and Metabolism Unit, Pitié-Salpêtrière University Hospital Group
(Assistance publique Hôpitaux de Paris (AP-HP)), Paris.
(3)Department of Neurophysiology, Pitié-Salpêtrière University Hospital Group
(Assistance publique Hôpitaux de Paris (AP-HP)), Paris.
(4)Department of Neurology, Reference Center for ALS Rare Disease,
Pitié-Salpêtrière University Hospital Group (Assistance publique Hôpitaux de
Paris (AP-HP)), Paris.
(5)Reference Center for Rare “Neurogenetic” Diseases, Department of Medical
Genetics, Pellegrin Hospital, Bordeaux University Hospital Center, Bordeaux.
(6)Rare Diseases Laboratory: Genetics and Metabolism, National Institute of
Health and Medical Research U1211, Bordeaux University, Bordeaux.
(7)Department of Neurology, Reference Center for Adult Leukodystrophies,
Montpellier University Hospital Center, National Institute of Health and Medical
Research, University of Montpellier, Montpellier.
(8)Department of Neurology, University Hospital, National Institute of Health and
Medical Research, Brain Imaging and Neurological Disabilities, Mixed Unit of
Research 1214, Toulouse.
(9)Department of Genetics, Reference Center for Neurogenetic Diseases, University
Hospital Angers, Angers.
(10)Biochemistry of Neurometabolic Diseases Functional Units, Department of
Metabolic Biochemistry, Pitié-Salpêtrière University Hospital Group (Assistance
publique Hôpitaux de Paris (AP-HP)), Paris.
(11)Biochemical, Metabolomic, and Proteomic Department, Necker University
Hospital Group (Assistance publique Hôpitaux de Paris (AP-HP)), Paris.
(12)National Institute of Health and Medical Research U1151, Necker University
Hospital Group, Paris Descartes University, Sorbonne Paris Cité, Paris, France.
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.
© 2020 American Neurological Association.
DOI: 10.1002/ana.25689
PMID: 31995250 [Indexed for MEDLINE]