Marion Masingue1, Louis Dufour2, Timothée Lenglet3,4, Lisa Saleille2, Cyril Goizet5,6, Xavier Ayrignac7, Fabienne Ory-Magne8, Magali Barth9, Foudil Lamari10, Daniele Mandia2, Catherine Caillaud11,12, Yann Nadjar2. 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.
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.
OBJECTIVE:GM2gangliosidoses 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 TSpatients), 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 SDpatients. 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: Olivia E Rowe; D Rangaprakash; Akila Weerasekera; Neha Godbole; Elizabeth Haxton; Peter F James; Christopher D Stephen; Robert L Barry; Florian S Eichler; Eva-Maria Ratai Journal: Mol Genet Metab Date: 2021-06-24 Impact factor: 4.204
Authors: Andrés Felipe Leal; Eliana Benincore-Flórez; Daniela Solano-Galarza; Rafael Guillermo Garzón Jaramillo; Olga Yaneth Echeverri-Peña; Diego A Suarez; Carlos Javier Alméciga-Díaz; Angela Johana Espejo-Mojica Journal: Int J Mol Sci Date: 2020-08-27 Impact factor: 5.923