Gangliosidoses GM2
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(Tay-Sachs disease, Sandhoff disease)
Rare lysosomal storage disease. Transmission: autosomal recessive.
Accumulation of GM2 ganglioside following:
- either to hexosaminidase A deficiency: variants B and B1 (more common in Jewish Ashkenases)
- either a deficiency in hexosaminidases A and B (gene on 5q13 ): variant O
- either a deficiency in prosaposine, activator of the enzyme required for the hydrolysis of the GM2: variant AB
1/ infantile form (type I, or Tay-Sachs disease): onset in the first months of life by inexhaustible outbursts to noise. Macrocephaly; hypotonia, spasticity, seizures. Nystagmus, oculo-motor disorders and blindness. Characteristic ophthalmoscopy finding: bilateral macular cherry red spot. Death before the age of 2 years.
2/juvenile form (type II) : onset between 2 and 6 years of age. Locomotor ataxia, behavioural disorders, mental regression leading to a loss of speech and decerebration. Death around 10-15 years.
3/ adult or chronic form (type III) : onset around age of 10 years but it is diagnosed much later. Two clinical pictures: 1) clinical picture of atypical Friedreich disease with spino-cerebellar ataxia, without heart or bone signs. (2) a clinical picture of juvenile spinal amyotrophy resembling Kugelberg-Welander syndrome. Intellectual degradation and possible behavioural or psychiatric disorders.
A treatment with miglustat seems to be effective in the juvenile and adult forms. A glucid-poor or even a cetogenic diet should be added as miglustat inhibits the intestinal disaccharidase and causes osmotic diarrheas in presence of glucids.
Anesthetic implications:
Mental retardation, spasticity, behavioural disturbances, risk of pulmonary inhalation.
References:
Updated: September 2018