Tay-sachs disease E75.0

Rare autosomal recessive inherited fatal neurodegenerative disease belonging to the lysosomal storage diseases (gangliosidosis), in which an accumulation of sphingolipids in the lysosomes occurs due to a lack of hexoseaminidase A. These sphingolipids are physiologically degraded by a sequential cleavage of the terminal sugars.

Increased incidence of the disease among Ashkenazi Jews of Eastern European origin (Lew RM et al. 2015). Further increase in French Canadians, Irish and Persians.

Several mutations of the gene located on chromosome 15q23-24, which codes for the enzyme β-N-acetylhexosaminidase, have been detected (Jamali S et al. 2014; Sheth J et al. 2018). The enzyme β-N-acetylhexosaminidase is responsible for the removal of terminal N-acetylgalactosamine residues. The absence of the enzyme or its loss of function leads to an accumulation of gangliosides in brain and retina. The consequence is a continuous loss of nerve cells.

From the 3rd month of life

Increasing muscle weakness, cherry-red spot in the macula, psychomotor deterioration with loss of the ability to sit and stand, conspicuous fright reactions to sound stimuli, blindness and deafness, pareses, spasticity, cramps, doll-like face with transparent skin, trichomegaly (long eyelashes) and fine hair. The affected children increasingly lose consciousness. They are increasingly unresponsive, are in a deep sleep. The motor and mental development of the children regresses, learned abilities are lost again. The children are dependent on permanent treatment. Complications often include infections of the respiratory tract.

Detection of the mutation. Detection of the reduced activity of hexosaminidase A or hexosaminidase B in blood serum, leukocyte or fibroblast cultures.

Progressive loss of cognitive abilities. Further psychomotor reduction, muscular hypotension, paralysis, spasticity, blindness, deafness and epileptic seizures. The sick children usually die between the 1st and 4th year of life due to recurrent respiratory infections.

Healthy carriers of the recessive gene can be identified by blood tests. To avoid the disease. If both parents are known carriers, pregnancy is not recommended. Families in which the disease has already occurred use the possibility of genetic counselling in the run-up to pregnancy or prenatal diagnostics.

Sphingolipids form a group of lipids that are involved in the formation of cell membranes. The lipids consist of fatty acid esterified with the alcohol sphingosine. The accumulation of these gangliosides in the lysosomes and later in the cytoplasm of the neurons leads to their death.

1. Jamali S et al (2014) Three novel mutations in Iranian patients with Tay-Sachs disease. Iran Biomed J 18:114-119.
2. Lew RM et al (2015) Ashkenazi Jewish population screening for Tay-Sachs disease: the internationaland Australian experience. J Paediatr Child Health 51:271-279.
3. Sheth J et al (2018) Identification of deletion-duplication in HEXA gene in five children with Tay-Sachs disease from India. BMC Med Genet 19:109.