This predominantly cerebellar disease of the sphingolipid metabolism is autosomal recessively inherited and caused by the accumulation of GM2 gangliosides in different organ systems including the central nervous system due to a beta-hexosaminidase A (HEXA gene) deficiency.
Signs and Symptoms
In homozygotes with full enzyme deficiency, disease onset is in early childhood and the patients die at about 4 years of age. Late-onset Tay-Sachs disease (Usually G269S mutation) manifests itself in adolescence (mean age 18.1 years).
The disease is characterized by different neurological signs that are not specific to the disease. These include spastic stance and gait, muscle atrophies with fasciculations, fatigue, cerebellar ataxia with postural instability and extrapyramidal symptoms. Patients may also present with psychiatric disorders such as psychotic episodes, depression and cognitive decline.
Ocular motor deficits include hypometric saccades featuring abrupt fluctuations in saccade velocity and premature termination. In late onset Tay-Sachs patients, saccades generally stop sooner and faster. In addition, they may display lower smooth pursuit gain and the slow phase of the optokinetik nystagmus may be reduced.
The frequency of Tay-Sachs disease is higher in Jewish communities with Eastern and Central European ancestors (Ashkenazi Jews), some French Canadian communities in Quebec and the Cajun community in Louisiana, USA.
Genetic testing and counselling are recommended in families with a history of Tay-Sachs disease. Diagnosis of the disease is reached by the observation of the characteristic “cherry-red” spot on the retina of the patient, ocular motor examinations and an enzyme assay to detect lowered levels of hexosaminidase A.
Observable ocular motor disorders
- Hypometric saccades
Strupp M, et al. (2014) Central ocular motor disorders, including gaze palsy and nystagmus. J Neurol 261(2):542-558. PubMed
Optican LM, et al. (2008) Mechanism of interrupted saccades in patients with late-onset Tay-Sachs disease. Prog Brain Res 171:567-570. PubMed