Tay-Sachs disease

Definition

Tay-Sachs disease is a rare, inherited, and fatal neurological disorder caused by the absence of a critical enzyme, resulting in the accumulation of harmful substances in the nerve cells of the brain. This genetic condition primarily affects the cytoplasm and cellular organelles, particularly the lysosomes, and exhibits distinct patterns of inheritance.

5 Must Know Facts For Your Next Test

1. Tay-Sachs disease is caused by a mutation in the HEXA gene, which is responsible for producing the enzyme hexosaminidase A (Hex-A).
2. The absence of Hex-A leads to the accumulation of a lipid molecule called GM2 ganglioside in the lysosomes of nerve cells, causing progressive damage and cell death.
3. Tay-Sachs disease is most common in individuals of Ashkenazi Jewish descent, with a carrier frequency of approximately 1 in 27 in this population.
4. Symptoms of Tay-Sachs disease typically appear in infancy and include developmental delays, seizures, blindness, and eventually, death, usually by the age of 4-5 years.
5. Prenatal genetic testing and carrier screening are important for identifying individuals at risk of Tay-Sachs disease, allowing for informed reproductive decisions and early intervention.

Review Questions

• Explain the role of lysosomes in the pathogenesis of Tay-Sachs disease.
  • In Tay-Sachs disease, the absence of the enzyme hexosaminidase A (Hex-A) leads to the accumulation of GM2 ganglioside, a lipid molecule, within the lysosomes of nerve cells. Lysosomes are organelles responsible for the breakdown and recycling of cellular components, but the buildup of GM2 ganglioside overwhelms the lysosomes, causing progressive damage and ultimately cell death in the affected neurons. This lysosomal storage disorder is a key feature of the pathology underlying Tay-Sachs disease.
• Describe the pattern of inheritance associated with Tay-Sachs disease and explain the implications for genetic counseling.
  • Tay-Sachs disease is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the mutated HEXA gene, one from each parent, to develop the condition. This has important implications for genetic counseling and reproductive decision-making. Individuals who are carriers of the Tay-Sachs mutation, possessing one normal and one mutated HEXA gene, are asymptomatic but can pass the disorder on to their children. Carrier screening and prenatal testing are crucial for identifying at-risk couples and allowing them to make informed choices about family planning and potential interventions to prevent the occurrence of Tay-Sachs disease.
• Evaluate the significance of the Ashkenazi Jewish population's higher carrier frequency for Tay-Sachs disease and discuss the potential public health implications.
  • The Ashkenazi Jewish population has a significantly higher carrier frequency for Tay-Sachs disease, with approximately 1 in 27 individuals being carriers. This increased prevalence is due to a founder effect, where a genetic mutation became more common within this population due to geographical and cultural isolation. The high carrier rate in the Ashkenazi Jewish community has important public health implications. It highlights the need for targeted genetic screening and counseling programs to identify carriers and provide them with information about the risks and options for family planning. Early detection and informed decision-making can help prevent the occurrence of Tay-Sachs disease and reduce the burden on affected individuals, families, and the healthcare system. Additionally, understanding the genetic factors contributing to Tay-Sachs disease in this population can provide valuable insights into the underlying mechanisms of the disorder and inform the development of potential treatments or interventions.

Related terms

Lysosome: A membrane-bound organelle in the cytoplasm that contains digestive enzymes and functions in the breakdown and recycling of cellular components.

Autosomal Recessive Inheritance: A pattern of inheritance where an individual must inherit two copies of a recessive allele, one from each parent, to express the associated trait or disorder.

Ganglioside: A type of glycolipid molecule found in the cell membrane, particularly abundant in nerve cells, that can accumulate in Tay-Sachs disease.