Tay-Sachs Disease (HEXA)
Tay-Sachs disease is an autosomal recessive disorder resulting from pathogenic variants in the HEXA gene. It has been reported in individuals from different ethnicities, but there is an increased prevalence of the disease in people of Ashkenazi Jewish, French Canadian, and Irish descent. Pathogenic HEXA variants result in loss of function of the beta-hexosaminidase A enzyme, causing accumulation of GM2 gangliosides in body tissues. Several different forms of the disease exist, including the infantile and later-onset variants. The infantile form, which is the most common, has an onset of symptoms around 6 months of age. Clinical features include progressive loss of coordination, seizures, difficulty swallowing and poor pulmonary function. Affected individuals eventually become blind, severely intellectually disabled, paralyzed and unaware of their surroundings. Death usually occurs at 3 to 5 years of age. The subacute (or juvenile) form usually has an age of onset between 2 and 10 years. The progression of the disease is similar to that of the infantile form, and death occurs between 10 and 15 years of age. In the chronic form, age of onset is similar to that of the juvenile form, but the symptoms progress more slowly. The clinical presentation is one of ataxia and dystonia. Survival is long-term. The adult-onset form is characterized by progressive muscle loss, weakness and difficulty speaking. Age of onset, symptoms and severity are variable among individuals. Survival is long-term. A genotype-phenotype correlation has been observed, where specific variants can be predicted to cause a later-onset form of the disease. Later-onset forms of the disease result when the residual beta-hexosaminidase A enzyme activity is between 5% and 15%. However, more than 90% of all pathogenic HEXA variants result in the infantile form of Tay-Sachs disease.
For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.