Genetic Disorders Assignment by Kathleen Vieira
Tay–Sachs disease, also known as GM2 gangliosidosis or hexosaminidase A deficiency, is a rare autosomal recessive gene disorder. In its most common variant, it causes a progressive deterioration of nerve cells and of mental as well as physical abilities that begins at around six months of age and usually results in death by the age of four.
Where is the gene located? Tay-Sachs is an inherited disease that only occurs when both parents carry a Tay-Sachs gene and each parent transmits the defective gene to their child. A child who inherits two Tay-Sachs genes produces no functional Hex-A enzyme and is certain to develop Tay-Sachs disease. Tay-Sachs disease results from defects in a gene on chromosome 15 that is in charge of the production of the enzyme Hex-A (National Centre for Biotechnology Information, 2015).
What type of mutation causes the disorder? Mutations in the Hex-A gene causes Tay-Sachs disease. The Hex-A gene provides instructions for making part of an enzyme called beta-hexosaminidase A, which plays a critical role in the brain and spinal cord. This enzyme is located in the lysosomes of a cell, where beta-hexosaminidase A helps break down a fatty substance called GM2 ganglioside.
Mutations in the Hex-A gene disrupt the activity of beta-hexosaminidase A, which prevents the enzyme from breaking down GM2 ganglioside. As a result, this substance accumulates to toxic levels, particularly in neurons in the brain and spinal cord affecting the individual. Progressive damage caused by the buildup of GM2 ganglioside leads to the destruction of these neurons, which causes the signs and symptoms of Tay-Sachs disease.
What is the function of the protein the gene codes for? The gene Hexosaminidase A (Hex-A), located in chromosome 15, encodes the alpha subunit of the lysosomal enzyme beta-hexosaminidase that, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Beta-hexosaminidase is composed of two subunits, alpha and beta, which are encoded by separate genes. This gene particularly effects the neurons in the brain and spinal cord, ultimately affecting the way the body functions.
What effect does the mutation have on the structure of the protein the gene codes for? Mutations in the Hex A gene disrupts the activity of beta-hexosaminidase A, which prevents the enzyme from breaking down GM2 ganglioside. The mutations in the DNA changes the sequence of the bases, which leads in changes in mRNA to differ as well. This results in an odd sequence of amino acids of proteins which means the primary structure of protein changes affecting the body greatly.
What is the mechanism of the disorder? This mutation occurs when the enzyme is absent or present in very small amounts, resulting in excessive accumulation of GM2 ganglioside in neurons, the mechanism of the disorder. Consequently the destruction of these neurons, which causes the signs and symptoms of Tay-Sachs disease (Tay-Sachs Disease, 2015).
Diagram of the Wild Type and Mutated Type Protein and the Pathway
What are the symptoms of the disorder? There are several symptoms of the Tay-Sachs disorder including the following:
Can the disorder be treated? If so, how?
Unfortunately, studies have thus far shown that there is no cure for the Tay-Sachs disorder (Herndon, 2012). There have been methods created for treatment and monitoring of this disorder including pain relief medications, medications to control seizures, physical therapy, feeding tubes, and respiratory care to reduce mucus buildup in the lungs. Physicians and Doctors have not given up trying to treat this disorder.