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Hereditary and Metabolic Diseases of the Central Nervous System in Adults
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Unlike the better known infantile and late adolescent variants, chronic GM2 gangliosidosis has variable onset and slow progression, with some surviving into their eighth decade. Most are HEXA compound heterozygotes with less than 10% enzyme activity.
Sandhoff disease/GM2 gangliosidosis/deficiency of Hex A and Hex B subunit deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
The clinical phenotype of Sandhoff disease may be indistinguishable from that of Tay-Sachs disease (Chapter 88), but there may be hepatosplenomegaly in Sandhoff disease. The distinction between the two conditions was delineated by Sandhoff et al. [1] in 1968, in a patient who was unusual in that he stored ganglioside not only in the brain but also in other viscera, in contrast to patients with Tay-Sachs disease. The activity of total hexosaminidase was found to be deficient [1]. Hexosaminidase B is a glycoprotein homopolymer with four identical subunits; its structure is designated β2β2 [2, 3]. Hexosaminidase A is a heteropolymer of α and β subunits. Activity of the Hex-A and Hex-B isozymes are defective because of a defective β subunit. The disease has also been referred to as GM2 gangliosidosis (variant O). The Hex-B gene is located on chromosome 5q13 [4]. Heterogeneity has been observed in the mutations in the gene for Hex-B [5]. Most mutations lead to the most severe infantile onset phenotype. The causative mutations in these patients tend to be deletions, nonsense mutations, or splice site mutations. The most common is a 16 kb deletion that includes the promoter, exons 1 to 5, and part of the intron [6].
Histiocytosis and Lipid Storage Diseases
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Salwa Shabbir Sheikh, David F. Garvin
GM2 gangliosidosis is a group of neurologic disorders divided into three major types: the B variant (Tay-Sachs disease), the O variant (Sandhoff disease), and the AB variant, caused by genetic abnormalities in the genes coding for b-hexosaminidase alpha or beta subunit, or the GM2 activator protein. Tay-Sachs disease (TSD) is the most common form of GM2 gangliosidosis.
Sandhoff disease in the elderly: a case study
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2022
Leidy García Morales, Reinaldo Gaspar Mustelier Bécquer, Laura Pérez Joglar, Tatiana Zaldívar Vaillant
Sandhoff disease is an infrequent genetically-caused disorder with a recessive inheritance pattern. It belongs to the gangliosidosis GM2 group and it is produced by mutations in gen HEXB (chromosome 5q13) leading to reduced activity of enzymes β-hexosaminidase A and B, and deposition of sphingolipids (ganglioside GM2 and globoside) in brain and other organs. Nearly, 40 specific mutations causing this disease have been reported (1). Clinical manifestations and age of onset depend on the enzymatic residual catabolic activity, associated with infantile, juvenile, and adult variants (2). The homozygous state is associated with earlier onset and greater disease severity (1). The clinical manifestations of the adult variant are heterogeneous and poorly characterized. It may appear as a combination of motor neuron disease, spinocerebellar ataxia, neuropathy, autonomic dysfunction, cognitive impairment, movement disorders, and psychiatric manifestations (2–4). At this time, there is no effective treatment for this disease (2).
Tuning the activity of iminosugars: novel N-alkylated deoxynojirimycin derivatives as strong BuChE inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Ana I. Ahuja-Casarín, Penélope Merino-Montiel, José Luis Vega-Baez, Sara Montiel-Smith, Miguel X. Fernandes, Irene Lagunes, Inés Maya, José M. Padrón, Óscar López, José G. Fernández-Bolaños
As aforementioned, glycosidases play a pivotal role in controlling not only the metabolic pathways where carbohydrates are present but also many other significant biochemical events, like cell-to-cell communication or recognition processes. Herein, a panel of five commercially-available glycosidases have been tested, as models of carbohydrate-mediated diseases: α-glucosidase (from Saccharomyces cerevisiae), β-glucosidase (from almonds), α-galactosidase (from green coffee beans) and β-galactosidase (from A. oryzae and from E. coli). Deficiencies in such enzymes are associated with diabetes, Gaucher’s disease, Fabry’s disease, and gangliosidosis, respectively3.
Ocular Manifestations of Neuronal Ceroid Lipofuscinoses
Published in Seminars in Ophthalmology, 2021
Rohan Bir Singh, Prakash Gupta, Akash Kartik, Naba Farooqui, Sachi Singhal, Sukhman Shergill, Kanwar Partap Singh, Aniruddha Agarwal
Until 1960s, the NCLs were considered to be variants of gangliosidoses such as Tay-Sachs disease owing to their shared symptom complex.7 However, it was found that the substances accumulating in NCLs were not metabolic precursors but physically, chemically and topographically similar to lipofuscin and ceroid (a pathological variant of lipofuscin).8