by Alexander Kurz

General outline

Tay-Sachs disease (TSD) is an autosomal recessive, progressive neurodegenerative disorder, which, in the classic infantile form, is usually fatal by age 2 or 3 years.

The adult form of the disease is very rare. Tay-Sachs disease is approximately 100 times more common in infants of Ashkenazi Jewish ancestry (central-eastern Europe) than in non-Jewish infants.

Symptoms and course

Classic TSD is characterised by the onset in infancy of developmental retardation, followed by paralysis, dementia and blindness, with death in the second or third year of life. A gray-white area arount the retinal fovea centralis, due to lipid-laden ganglion cells, leaving a central “cherry-red” spot is a typical fundoscopical finding. Affected childred show slowly progressive deterioraion of gait and posture.

Muscular atrophy begins. There may be spasticity, mild ataxia of limbs and trunk, dystonia, and dysarthria. In young adults clinical features are progressive leg weakness and fasciculations consistent with anterior horn disease. Patients may also show cerebellar atrophy, dementia, and denervation motor neuron disease.

Causes and risk factors

The basic enzyme defect in TSD involves the enzyme hexosaminidase A (hex A). It results in the accumulation of a glycoprotein. More than 80 different mutations have been found in the hexosaminidase A gene (15q23-q24).

Diagnostic procedures

Reduced sphingomyelin in red blood cells may be used as a laboratory test to identify mutation carriers. Among Ashkenazi carriers identified by the enzyme test 82 % have one of the known hex A mutations. Today, DNA testing alone is considered as the most cost-effective and efficient approach to carrier screening fo TSD in individuals of confirmed Ashkenazi Jewish ancestry. TSD was the first genetic condition for which community-based screening for carrier detection was implemented.

Treatment and rehabilitation

To date no effective treatment is available for TSD. Experimental strategies include bone marrow transplantation, enzyme replacement, and gene therapy.

Available services

Neurology and pediatrics departments.

References

• Barnes, D.; Misra, V. P.; Young, E. P.; Thomas, P. K.; Harding, A. E. : An adult onset hexosaminidase A deficiency syndrome with sensory neuropathy and internuclear ophthalmoplegia. J. Neurol. Neurosurg. Psychiat. 54: 1112-1113, 1991
• Brady, R. O. : Cerebral lipidoses. Ann. Rev. Med. 21: 317-334, 1970
• Hultberg, B. : N-acetylhexosaminidase activities in Tay-Sachs disease. (Letter) Lancet II: 1195, 1969
• Kaback, M. M.; Rimoin, D. L.; O'Brien, J. S. : Tay-Sachs Disease: Screening and Prevention. New York: Alan R. Liss (pub.) 1977
• F Kaplan: Tay-Sachs disease carrier screening: a model for prevention of genetic disease. Genet Test 2: 271-292, 1998
• Suzuki, Y.; Suzuki, K. : Partial deficiency of hexosaminidase component A in juvenile Gm(2)-gangliosidosis. Neurology 20: 848-851, 1970