Home > Tay-Sachs disease

1 Signs and symptoms

Infants with Tay-Sachs disease appear to develop normally for the first few months of life. Then, as nerve cells become distended with fatty material, a relentless deterioration of mental and physical abilities occurs. The child becomes blind, deaf, and unable to swallow. Muscles begin to atrophy and paralysis sets in.

A much rarer form of the disorder which occurs in patients in their twenties and early thirties is characterized by unsteadiness of gait and progressive neurological deterioration. Patients with Tay-Sachs have a "cherry-red" spot in the back of their eyes (the retina).

2 Pathogenesis

The condition is caused by insufficient activity of an enzyme called hexosaminidase A that catalyzes the biodegradation of acidic fatty materials known as ganglioside s. Gangliosides are made and biodegraded rapidly in early life as the brain develops. Patients and carriers of Tay-Sachs disease can be identified by a simple blood test that measures hexosaminidase A activity. Both parents must be carriers in order to have an affected child. When both parents are found to carry a genetic mutation in hexosaminidase A, there is a 25 percent chance with each pregnancy that the child will be affected with Tay-Sachs disease. Prenatal monitoring of pregnancies is available if desired.

To expand somewhat on the genetic basis, Tay-Sachs is an autosomal recessive genetic condition. Both parents must be carriers in order for a child to inherit the condition. If both parents are carriers, there is a 25% risk with each pregnancy for an affected child.

The disease results from mutation of the HEXA gene encoding the alpha-subunit of the lysosomal enzymeAn enzyme is a protein, or protein complex, that catalyzes a chemical reaction. Like any catalyst, enzymes work by lowering the activation energy of a reaction, thus allowing the reaction to proceed to its steady state or completion much faster than it ot alpha-N-acetylhexosaminidase. This enzyme is necessary for breaking down N-galactosamine from GM2 gangliosides in brain and nerve cells. More than thirty mutations have been identified in the HEXA gene. These consist of base pairIn genetics, two nucleotides on opposite complementary DNA or RNA strands that are connected via hydrogen bonds are called a base pair (often abbreviated bp). As DNA is usually double-stranded, the number of base pairs in the dsDNA strand equals the numbe insertions, base pair deletions, splice site mutations, and point mutations. All of these mutations alter the protein product. For example, a four base pair insertion in exon 11 results in an altered reading frame for the HEXA gene while a three base pair deletion eliminates the amino acid phenylalinine from the protein product at position 304. A G to C point mutation at amino acid 180 changes the codon UAC to UAG causing termination of the polypeptide. A G to A point mutation at amino acid 170 changes the codon CGA to CAA and CGG to CAG which produces glutamineGlutamine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side chains functional group. It has been suggested glutamine is utilized at a higher than normal rate in people living with diseases that strain the immune sys instead of arginineArginine is one of the 20 most common natural amino acids. Is has guanidino side chain functional group. In non-hepatic tissues, arginine can be biosynthesized by the ornithine cycle (or urea cycle). Even so, arginine is often classed as one of the 10 ess. A G to C mutation in the splice site of intronIntrons are sections of DNA within a gene that do not encode part of the protein that the gene produces, and are spliced out of the mRNA that is transcribed from the gene before it is exported from the cell nucleus. Introns exist mainly (but not only) in 12 has also been identified. This mutation creates a recognition site for the restriction enzyme DdeI resulting in abnormal splicing and the production of aberrant mRNA species.