Familial amaurotic idiocy is an old term for Tay-Sachs disease, which is succinctly described by the Online Mendelian Inheritance in Man (OMIM) as a severe neurodegenerative condition that is usually deadly by the age of 2 or 3 years in its classic infantile form due to a lack of the hexosaminidase A enzyme. The term "autosomal" indicates that the gene responsible for Tay-Sachs disease is located on a non-sex chromosome, specifically chromosome 15q23-q24. "Recessive" means that the disease appears in individuals who have two copies of the gene, while those with one copy are healthy carriers. Over time, the condition worsens as the nervous system continues to break down.The "classic" form of Tay-Sachs disease begins subtly in infancy. At first, the child appears to develop normally for several months, but an exaggerated startle response often becomes noticeable. By 6-8 months, the infant loses head control and is unable to roll over or sit up. Muscle stiffness and rigidity develop, along with excessive drooling and seizures. Blindness and an increase in head size manifest by the second year. While traditionally considered fatal by age 2 or 3, it is now recognized that some children may survive until age 5. After age 2, constant nursing care becomes essential, and death usually results from pneumonia or complications due to aspiration.Tay-Sachs disease stems from the absence of the enzyme hexosaminidase A, which is crucial for processing a specific lipid, GM2-ganglioside. The accumulation of this lipid in the brain and other tissues causes significant harm. Tay-Sachs disease is a prime example of a fatal metabolic disorder that predominantly affects a specific subpopulation, occurring more frequently among individuals of Jewish descent, particularly Ashkenazi Jews, who make up 95% of the Jewish population in the United States. The occurrence of the disease is much rarer in non-Jewish individuals.Understanding the genetic foundation of Tay-Sachs disease has led to the development of carrier screening programs and prenatal diagnosis options. There are also forms of the disease with higher levels of hex-A enzyme and later onset, known as juvenile and adult Tay-Sachs disease. Alternative names for the condition include type 1 GM2-gangliosidosis, B variant GM2-gangliosidosis, hexosaminidase A deficiency, and hex-A deficiency.Tay-Sachs disease was named after the English physician Waren Tay and New York neurologist Bernard Sachs. In 1881, Tay observed an infant with progressive visual impairment and described the "cherry-red spots" in the eyes typical of the disease. Sachs encountered similar cases in 1887 and 1898 and, by 1910, identified the lipid accumulation in the brain associated with the condition.
