Diagnosing Late-Onset Tay-Sachs Through Next Generation Sequencing and Functional Enzyme Testing: From Genes to Enzymes.

Tay-Sachs disease is a neurodegenerative disorder characterized by progressive neurologic impairment due to pathogenic variants in the HEXA gene that codes for the alpha subunit of β-hexosaminidase. We report 2 cases of adult-onset progressive weakness, ataxia, and neuropsychiatric symptoms in a 30-year-old man and 37-year-old woman. Both patients had compound heterozygosity in the HEXA gene with 4 distinct variants. The first patient had subsequent confirmatory functional enzyme testing displaying reduced hexosaminidase concentration, and the second patient had functional enzyme testing before genetic testing, exemplifying alternative avenues for the diagnosis of late-onset Tay-Sachs (LOTS) disease.