Enfermedad de Tay-Schens

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Biología celular y molecular

Ciencias biológicas

Clinical, biochemical, and molecular findings in a Colombian patient with Tay-Sachs disease (Elsevier, 2018)

https://www.elsevier.es/en-revista-neurologia-english-edition--495-articulo-clinical-biochemical-molecular-findings-in-S2173580817301505

Tay-Sachs disease is an autosomal recessive neurodegenerative disorder characterised by a mutation or deletion of the hexosaminidase A gene (HEXA), located at 15q23. The gene codes for the alpha subunit of hexosaminidase A, a lysosomal enzyme involved in ganglioside metabolism. (Posso Gómez L.J. 2018)

Tay-Sachs disease is a lysosomal storage disease and generally manifests after a period of normal neurological development. In this disease, gangliosides (GM2), a type of sphingolipid present in the membranes of cells of the central nervous system, are stored due to the lack of hexosaminidase A. The accumulation of gangliosides causes irreversible neurological damage and death at young ages. (Gómez J.F. 2018)

Tay-Sachs disease, described in 1881 by Tay and in 1887 by Sachs, is currently one of the most widely studied sphingolipidoses within the context of lysosomal storage diseases.6 The characteristic inheritance pattern of this disease, as in most inborn errors of metabolism, follows an autosomal recessive inheritance pattern. Mutation of the HEXA gene is responsible for the disease. (Botero V. 2018)

One of the ophthalmological signs described in this disease are the cherry-red spots at the macula which correspond to the abnormal accumulation of metabolic products inside the retinal ganglion cells.9 However, in this particular case, these spots were not present, although the physical examination of the eye did reveal alterations in the fovea in a “bull's eye” shape, which may be secondary to drug-related toxicity or optical degeneration. (Pachajoa H. 2018)

Tay-Sachs disease must be included in the differential diagnosis of paediatric neurological disorders causing regression of developmental milestones. It is important to include molecular testing as part of diagnostic protocols for the disease and genetic counselling as a means to prevent familial recurrences of the disease. (Gómez J.F. 2018)

Tay-Sachs disease (UNAL, 2018)

https://revistas.unal.edu.co/index.php/revfacmed/article/view/69742

TSD is an autosomal recessive, neurodegenerative disorder that is part of a group of three lysosomal storage diseases known as gangliosidoses GM2. These diseases are caused by a defect in GM2-catabolism, which is in turn caused by the deficiency of the lysosomal β-hexosaminidase A (HexA) enzyme, whose function is to transform ganglioside GM2 into ganglioside GM3, thus triggering the abnormal accumulation of gangliosides GM2, mainly in neurons; this leads to cell death and to the development of the disease. (Calderon Nossa T. 2019)

Lysosomal storage disease is caused by the deficiency of a single hydrolase (lysosomal enzymes). GM2 gangliosidoses are autosomal recessive disorders caused by deficiency of β-hexosaminidase and Tay-Sachs disease (TSD) is one of its three forms. (Gualdrón Frías C.A. 2019)

Lysosomes contain a wide variety of active hydrolytic enzymes known as hydrolases, including glycosidases, phosphatases, sulphatases, lipases, proteases, phospholipases, and nucleases. Deficiency of only one of these hydrolases results in the inability to degrade macromolecules and, as a consequence, a lysosomal storage disease. GM2 gangliosidoses are autosomal recessive disorders caused by the deficiency of β-hexosaminidase, which in turn lead to excessive intralyosomal accumulation, particularly in neuronal cells. (Calderon Nossa T. 2019)

TSD was first described in 1881, but its etiology remained unknown for a long time, and affected newborns could only be diagnosed after the first clinical manifestations. That changed in 1969 when the deficiency of the hexosaminidase enzymatic activity was discovered, allowing the initiation of the assessment of carrier states. For this reason, Tay-Sachs disease is considered a prototype disease for targeted ethnic evaluations. (Gualdrón Frías C.A. 2019)

TSD occurs most often in children with intellectual disability, skill regression, dementia, paralysis and blindness, and it, usually, leads to death by age 5. (Calderon Nossa T. 2019)

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