by Alexander Kurz
Sandhoff disease is an autosomal recessive neurodegenerative disorder characterised by an accumulation of GM2 gangliosides, particularly in neurons, and is clinically indistinguishable from Tay-Sachs disease.
The biochemical deficit is the absence of beta hexosaminidase A and B activity which results in the abnormal sotrage of GM2 gangliosides.
Neurodegeneration begins in infancy and leads to death generally by 4 – 6 years of age. The ganglioside, which is abnormally stored, is different from Tay-Sachs disease. There are infantile, late infantile, juvenile, and adult variants of generalised gangliosidosis.
Symptoms and course
In the adult variant childhood development may be normal. In early adulthood patients may develop impairment in articulation or stuttering, and in limb coordination, hyperactive deep tendon reflexes, progressive dysarthria, moderate ataxia, and intention tremor. Intellectual impairment is usually mild.
Neurodegeneration begins in infancy and leads to death generally by 4 – 6 years of age.
Causes and risk factors
While Tay-Sachs disease results from a mutation in tha alpha subunit of the hexosaminidase gene (hex A), Sandhoff disease is caused by mutaion in the beta subunit of the hexosaminidase A (15q23-q24, leading to a partial deficit of the enzyme) and B (5q11) enzymes. Therefore, hxosaminidases A and B are both deficient in Sandhof disease.
The diagnosis is established by an enzymatic test.
Care and treatment
Most research effort has focused on strategies for augmenting enzyme levels to compensate for the underlying defect. These include bone marrow transplantation, enzyme replacementt, and gene therapy. An alternative strategy is substrate deprivation which aims at balancing the rate of ganglioside synthesis with the impaired rate of ganglioside breakdown. Studies in humans are planned.
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Last Updated: vendredi 09 octobre 2009