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

Ajay R Tupil; Warwick Rivlin; Pamela A Mccombe; Robert D Henderson; Jonathan Rodgers; Lata Vadlamudi

doi:10.1212/NXG.0000000000200205

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

Neurol Genet. 2024 Oct 23;10(6):e200205. doi: 10.1212/NXG.0000000000200205. eCollection 2024 Dec.

Authors

Ajay R Tupil¹, Warwick Rivlin¹, Pamela A Mccombe¹, Robert D Henderson¹, Jonathan Rodgers¹, Lata Vadlamudi¹

Affiliation

¹ From the School of Medicine (A.R.T., J.R.), The University of Queensland; Department of Neurology (W.R., P.A.M., R.D.H., L.V.), Royal Brisbane & Women's Hospital; The University of Queensland (P.A.M., R.D.H., L.V.), UQ Centre for Clinical Research; and Genetic Health Queensland (J.R.), Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia.

Abstract

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.