SciTech

Health Talk: Tay-Sachs disease

Possibly one of the most devastating genetic disorders, Tay-Sachs disease is fatal, and children who are diagnosed with the disease rarely live beyond four years. Children with Tay-Sachs disease appear normal at birth, but when they are around 3 to 6 months old, they develop symptoms ranging from deafness and blindness to seizures and dementia, which eventually results in death. The Mayo Clinic elaborates on certain other symptoms of the disease that include decreased eye contact in infants, lack of crawling or smiling, and exhibiting slow body growth. According to the National Institute of Neurological Disorders and Stroke, those suffering from this disorder also have a characteristic “cherry-red spot” in their eyes. In fact, it was this cherry-red spot that first led to the characterization of the disease by British ophthalmologist Warren Tay in 1881.

Considering the debilitating effects of the disorder, it is hard not to wonder what causes the disease. The Genetics Home Reference website describes Tay-Sachs as a disease caused by the build-up of a fatty substance called GM2 ganglioside in the brain. The buildup of the ganglioside is caused by disrupted activity of the enzyme beta-hexosaminidase A, which is present in the lysosomes of cells and is normally responsible for degrading GM2 ganglioside. If beta-hexosaminidase A malfunctions, GM2 ganglioside builds up inside the cells to toxic levels. This buildup is particularly prominent in neurons in the brain and spinal cord, and hence the disease affects the nervous system. The hereditary component of the disease is due to the fact that individuals with the disease have a mutation in the HEX A gene, which is responsible for creating the beta-hexosaminidase A enzyme. A mutation in the HEX A gene causes defects in the formation of the enzyme, which prevents the enzyme from being able to degrade GM2 ganglioside.

In spite of the diseases being fatal, according to the National Genome Research Institute, one in 250 people possesses the mutated version of HEX A. With such a high rate of occurrence, it would seem that the disease is fairly common and should affect a large number of people. To understand why this is not the case, we need to go back to the basics of genetics, which state that genes always come in pairs; hence, there is a pair of HEX A genes in the body. If only one of these genes is mutated, the person is perfectly normal and shows no symptoms of the disease. People with just one copy of the gene are called carriers of the disease. The disease manifests itself only when a person contains two mutated copies of the gene. Children receive one of gene of the pair from one parent and the other from the other parent. Thus a child of one carrier parent and one parent without the mutated gene will be perfectly normal; children of two carriers, however have a 25 percent chance of contracting the disease. As stated on www.tay-sachs.org, the disease is fairly common in those of Eastern European Jewish descent, with one in 27 of them being carriers. Currently, there is no cure for the disease, and the disease is fatal for anyone with two defective copies of the HEX A gene. Tests for detecting whether one is a carrier of the gene do exist. The tests are simple blood tests and can easily help couples decide whether they want to have children if both parents turn out to be carriers.

Although the form of Tay-Sachs described here is the most common form seen, a rarer form also exists which affects those of an older age group. Juvenile Tay-Sachs occurs due to a deficiency, rather than a complete lack, of the functioning beta-hexosaminidase A enzyme. Symptoms for juvenile Tay-Sachs usually develop between the ages two to five years and such children usually live up to around 15 years of age. Another even milder form of Tay-Sachs affects children and adults alike, from anywhere between the ages of 5 to 30 years. The symptoms of this version of the disease are also milder and include slurred speech, an unsteady gait, and sometimes mental disorders.