CPT® Code 81255

HEXA (hexosaminidase A [alpha polypeptide]) (eg, Tay-Sachs disease) gene analysis, common variants (eg, 1278insTATC, 1421+1G>C, G269S)

The CPT® Code 81255 pertains to the molecular genetic testing of the HEXA gene, specifically analyzing common variants associated with Tay-Sachs disease (TSD). Tay-Sachs disease is classified as a lysosomal storage disorder, which is characterized by the accumulation of GM2 ganglioside due to a deficiency or near absence of the beta-hexosaminidase A enzyme. This accumulation occurs in the nerve cells of the brain, leading to premature cell death and a progressive decline in mental and physical abilities. The condition is inherited in an autosomal recessive manner, meaning that an individual must inherit mutations in the HEXA gene from both parents to develop the disease. Those who inherit a mutation from only one parent are considered carriers and typically do not exhibit symptoms. The HEXA gene is located on chromosome 15, and over 100 mutations have been identified, with the most common variants being 1278insTATC and 1421+1G>C. The former variant is predominantly found in the Cajun population of Louisiana and among individuals of Ashkenazi Jewish descent. When individuals are homozygous for these mutations, they may develop Acute Infantile TSD, which manifests between 3 to 6 months of age, leading to severe neurological decline and typically resulting in death by age 4. Additionally, the G269S mutation, when paired with certain null alleles, can lead to Subacute Juvenile or Adult/Late Onset TSD, which presents with varying symptoms and has different prognoses. Molecular genetic testing is crucial for identifying these mutations, distinguishing between pseudo deficiency alleles and pathogenic mutations, and providing genetic counseling to affected individuals and their families.