TaySachs

Tay-Sachs disease is a rare inherited neurodegenerative disorder caused by mutations in the HEXA gene, which lead to a deficiency of the enzyme beta-hexosaminidase A. This enzymatic defect prevents the breakdown of GM2 ganglioside within lysosomes, resulting in GM2 accumulation in neurons and progressive neural damage. The condition is part of a broader group known as GM2 gangliosidoses.

Tay-Sachs is inherited in an autosomal recessive pattern. Carrier frequency is notably higher in certain populations, particularly people of Ashkenazi Jewish descent, but the disorder can occur in any ethnic group. Genetic testing and counseling are available for at-risk couples and for guiding prenatal decisions.

The most common form is the infantile variant, with onset typically between 3 and 6 months of age. Early signs include developmental delay, loss of motor skills, decreased muscle tone (hypotonia), exaggerated startle responses, and poor visual tracking. A characteristic cherry-red spot at the retina may be observed. Progression leads to seizures, blindness, severe intellectual and motor decline, and death usually by age 4. There are also juvenile and adult-onset forms, which have slower progression and more variable symptoms, including ataxia, motor difficulties, and psychiatric or neurological features.

Diagnosis is based on measuring beta-hexosaminidase A activity in blood or leukocytes; a deficient activity suggests Tay-Sachs and can be confirmed with genetic testing for HEXA mutations. Imaging and other tests may support evaluation of neurological involvement.

There is no cure for Tay-Sachs disease. Management is supportive and multidisciplinary, focusing on symptom relief and quality of life. Population screening programs and carrier testing have contributed to reducing incidence in high-risk groups, complemented by genetic counseling for family planning. The disease was named after Warren Tay, who first described the retinal cherry-red spot, and Bernard Sachs, who contributed to understanding its neuropathology, with the genetic basis characterized in later decades.