Diagnostic Difficulties in a Child with Tay-Sachs Disease

Case Presentation: We present a girl with severe developmental delay with regression, leukodystrophy, epileptic encephalopathy, blindness, and a cherry red macula spot. Metabolic testing was normal apart from an elevated chitotriosidase. Total hexosaminidase was normal. We suspected a GM2-gangliosidosis type Tay-Sachs disease and retested the total hexosaminidase activity and hexosaminidase A separately and found a very low hexosaminidase A activity, which confirmed the diagnosis of Tay-Sachs disease. Exome sequencing identified a previously reported pathogenic homozygous missense mutation (c935T>G, pMet312Arg; CM930397) in HEXA A, thereby, confirming the diagnosis on the molecular level. Conclusion: In clinical suspicion of Tay-Sachs disease, it is useful not only do test the total hexosaminidase but to test hexosaminidase A separately.