Tay–Sachs Disease

Tay–Sachs disease is an inherited, progressive neurological disorder. Variants in both copies of the HEXA gene on chromosome 15 reduce or remove the activity of the lysosomal enzyme beta-hexosaminidase A. Without enough enzyme, GM2 ganglioside cannot be broken down and builds up inside lysosomes, mainly in neurons of the brain and spinal cord. The accumulation progressively damages and destroys those neurons. A person with one variant copy is an unaffected carrier, not a person with the disease. The mechanism explains the course. As neurons are lost, a child loses skills already gained, develops an exaggerated startle response to noise, muscle weakness and involuntary muscle jerks (myoclonus), and then seizures, vision loss, hearing loss and intellectual disability. Weakening of the muscles used for swallowing and coughing leads to pooled saliva and mucus, aspiration and aspiration-related respiratory infection. On eye examination, a cherry-red spot at the macula is a classic finding. The forms differ by age at onset and speed of progression. Infantile disease, the most common form, usually begins between 3 and 6 months of age after a period of apparently...