- Tay-Sachs disease (TSD) is caused by a genetic mutation on the hexa gene on chromosome 15. This mutation leads to the insufficient activity of the enzyme hexosaminidase A. This enzyme is necessary formetabolism of gangliosides, water-soluble glycolipids found primarily in central nervous system (CNS) tissues. Without hexosaminidase A, accumulating lipid pigments distend and progressively destroy and demyelinate CNS cells.
- TSD is inherited in an autosomal recessive pattern, with an increased prevalence in the Eastern European Jewish (Ashkenazi) population.
- Affects approximately l in 3,600 individuals of Ashkenazi Jewish ancestry
- 1 in 27 to 1 in 30 Ashkenazi Jews are recessive carriers
- Irish Americans have a 1 in 50 chance of being a carrier
- In the general population, the incidence of carriers (heterozygotes) is about 1 in 300
- All patients with Tay-Sachs disease have a “cherry-red” spot. This red spot is the area of the retina which is accentuated because of gangliosides in the surrounding retinal ganglion cells (which are neurons of the central nervous system). The choroidal circulation is showing through “red” in this region of the fovea where all of the retinal ganglion cells are normally pushed aside to increase visual acuity. Thus, the cherry-red spot is the only normal part of the retina seen.
- Infantile TSD: infants with Tay-Sachs disease appear to develop normally for the first six months of life. Then, as nerve cells become distended with gangliosides, a relentless deterioration of mental and physical abilities occur. The child becomes blind, deaf, and unable to swallow. Muscles begin to atrophy and paralysis sets in. Death usually occurs before the age of 4 or 5.
- Juvenile TSD: extremely rare, Juvenile Tay-Sachs disease usually presents in children between 2 and 10 years of age. They develop cognitive, motor, speech difficulties (dysarthria), swallowing difficulties (dysphagia), unsteadiness of gait (ataxia), and spasticity. Patients with Juvenile TSD usually die between 5–15 years.
- Adult/Late Onset TSD: a rare form of the disorder, known as Adult Onset Tay-Sachs disease or Late Onset Tay-Sachs disease (LOTS), occurs in patients in their 20s and early 30s. Late onset TSD is frequently misdiagnosed, and is usually non-fatal. Symptoms of LOTS, which present in adolescence or early adulthood, include speech and swallowing difficulties, unsteadiness of gait, spasticity, cognitive decline, and psychiatric illness, particularly schizophrenic-like psychosis. Patients with LOTS frequently become full-time wheelchair users in adulthood, but many live full adult lives if psychiatric and physical difficulties are accommodated
- There is currently no cure or treatment for TSD. Even with the best care, children with Infantile TSD die by the age of 5, and the progress of Late-Onset TSD can only be slowed, not reversed. Since Tay-Sachs disease is a lysosomal storage disorder, the research strategies have been those for lysosomal storage disorders in general. Several methods of treatment have been investigated for Tay-Sachs disease, but none have passed the experimental stage:
- Enzyme replacement therapy: The goal would be to replace the missing enzyme, a process similar toinsulin injections for diabetes. However, the HEXA enzyme has proven to be too large to pass the blood-brain barrier.
- Gene therapy: Several options for gene therapy have been explored for Tay-Sachs and other lysosomal storage diseases. If the defective genes could be replaced throughout the brain, Tay-Sachs could theoretically be cured. However, researchers working in this field believe that they are years away from the technology to transport the genes into neurons, which would be as difficult as transporting the enzyme
- Substrate reduction therapy: Other highly experimental methods being researched involve manipulating the brain’s metabolism of GM2 gangliosides. One experiment has demonstrated that, by using the enzyme sialidase, the genetic defect can be effectively bypassed and GM2 gangliosides can be metabolized so that they become almost inconsequential.