Clinical Information

Tay-Sachs disease (TSD) is an inherited lysosomal storage disease caused by a deficiency of the enzyme beta-hexosaminidase A. It is characterized by accumulation of GM2 gangliosides in cells of the brain and central nervous system. The HEXA gene encodes the alpha subunit of beta-hexosaminidase A and mutations in this gene cause TSD. TSD occurs in approximately 1 in 200,000 live births with a carrier frequency of 1 in 250 to 1 in 300 in the general population. The carrier frequency for this disease in individuals of Ashkenazi Jewish ancestry is 1 in 31.

The classic form of TSD becomes apparent in infancy when mild motor weakness is noted along with impaired visual acuity and the presence of a "startle response." Other manifestations include progressive neurodegeneration, seizures, and blindness, leading to total incapacitation and death. The subacute and adult-onset types of TSD are characterized by later ages of onset and a broad spectrum of disease symptoms and severity.

TSD is inherited in an autosomal recessive manner. Several common mutations in the HEXA gene account for 92% of disease-causing mutations in the Ashkenazi Jewish population. Testing for these mutations is available as a panel, TSDP / Tay-Sachs Disease, Mutation Analysis, HEXA. In non-Ashkenazi Jewish individuals, the detection rate for the common mutations is significantly decreased. Sequencing of the entire HEXA gene detects less common disease-causing mutations.

The recommended first-tier test for TSD carrier screening and diagnosis in all patients is a biochemical test that measures hexosaminidase A activity in white blood cells, NAGW / Hexosaminidase A and Total Hexosaminidase, Leukocytes.