TTPA

The TTPA gene provides instructions for making the α-tocopherol transfer protein (αTTP), which is found in the liver and brain. This protein controls the distribution of vitamin E obtained from the diet (also called α-tocopherol) to cells and tissues throughout the body. Vitamin E is an antioxidant that protects cells in the body from the damaging effects of unstable molecules called free radicals. Normally, vitamin E derived from food is absorbed in the intestine and then transported into the liver on molecules called chylomicrons. After a meal, chylomicrons are formed to transport fat-soluble vitamins (such as vitamin E), dietary fats, and cholesterol from the intestine to the liver. Once in the liver, αTTP transfers vitamin E from chylomicrons to very low-density lipoproteins (VLDLs), which carry fat, fat-soluble vitamins, and cholesterol from the liver to other tissues throughout the body. The VLDLs are then released into the bloodstream so the accompanying vitamin E can be used in the body. The αTTP protein is also thought to transport vitamin E to nerve cells (neurons) in the brain.

ataxia with vitamin E deficiency - caused by mutations in the TTPA gene

At least 18 mutations in the TTPA gene have been found to cause ataxia with vitamin E deficiency. Some of these mutations cause no functional protein to be made, while others change a single protein building block (amino acid) in the αTTP protein, reducing its function. One mutation that is found in the Japanese population changes the amino acid histidine to the amino acid glutamine at position 101 in the αTTP protein (written as His101Glu or H101Q). Along with causing ataxia with vitamin E deficiency, this mutation is associated with the development of an eye disorder called retinitis pigmentosa that causes vision loss.

Mutations in the TTPA gene that cause no functional αTTP protein to be made are associated with a severe form of ataxia that begins at a young age. Mutations that reduce but do not eliminate the protein's function are associated with milder ataxia that occurs at a later age and progresses more slowly.