HEXA

About HEXA

HEXA on chromosome 15q23 encodes the alpha subunit of beta hexosaminidase A, a lysosomal enzyme that degrades GM2 ganglioside, a lipid abundant in nerve cell membranes. Variants on both copies cause Tay Sachs disease, an autosomal recessive neurodegenerative disorder in which GM2 ganglioside accumulates in neurons. The classic infantile form presents in the first months of life with developmental regression, loss of motor skills, an exaggerated startle response, and a cherry red spot on the macula, followed by seizures, blindness, and death usually in early childhood. Juvenile and late onset forms with residual enzyme activity progress more slowly. The disease is named after the British ophthalmologist Warren Tay, who described the cherry red spot in 1881, and the American neurologist Bernard Sachs. Carrier frequency is elevated in Ashkenazi Jewish, French Canadian, and Cajun populations. Carriers can be identified by enzyme assay and DNA testing, and community carrier screening programs beginning in the 1970s led to a dramatic fall in the incidence of the disease in Jewish populations. No disease modifying treatment is established for the classic form, and gene therapy and substrate reduction approaches are being investigated.