[MIM 272 800]

(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

• variant B: deficiency in β-hexosaminidase A (HEXA gene on 15q23 ): three forms depending on the age of onset and correlated to the importance of hexosaminidase A deficiency:

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.

• variant B1: clinical presentation similar to the juvenile or adult of variant of B forms
• variant AB: clinical presentation similar to Tay-Sachs disease
• variant O (or Sandhoff disease) : the early form is similar to Tay-Sachs disease; in late forms: spinocerebellar ataxia  or dystonia; sometimes intellectual impairment. 

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:

•        Bley AE , Giannikopoulos OA, Hayden D, Kubilus K, Tifft CJ, Eichler FS.
  Natural history of infantile G(M2) gangliosidosis. 
  Pediatrics 2011 ;128 :e1233-41. 
•        Jarnes Utz JR, Kim S, King K, Ziegler R et al.
  Infantile gangliosidoses : mapping a timeline of clinical changes.
  Mol Genet Metabol 2017; 121: 170-9.

Updated: September 2018