Ataxia with vitamin E deficiency (ataxia with Vitamin E deficiency) - Gen APTT            

Ataxia with Vitamin E deficiency (Ataxia with Vitamin E deficiency, AVED) is a neurodegenerative disease characterized mainly by progressive spinocerebellar ataxia, areflexia, and a marked deficit of vitamin E. Vitamin E deficiency can lead to neurological problems, such as ataxia, dysarthria, loss of reflexes in the legs (areflexia) and peripheral neuropathy. Some affected individuals develop an eye condition called retinitis pigmentosa, which causes loss of vision. Most people with ataxia with vitamin E deficiency begin to show problems with movement between the ages of 5 and 15 years. Movement problems tend to worsen with age.

This process is due to mutations in the gene APTT (?-tocopherol transfer protein), located on the long arm of chromosome 8 (8q12.3). This gene encodes the protein ?-tocopherol transfer (?TTP), found in the liver and brain. This protein controls the distribution of vitamin E obtained from the diet, called ?-tocopherol, to body tissues and cells. Vitamin E is an antioxidant that protects body cells from the damaging effects of free radicals. Typically, vitamin E from food is absorbed in the intestine and transported in the liver called chylomicrons molecules. After food intake, chylomicrons to transport fat - soluble vitamins, such as vitamin E, dietary fats and cholesterol, are formed from the intestine to the liver. Once in the liver, vitamin E ?TTP transferred from chylomicrons, very low density (VLDL lipoproteins) that transport lipids, vitamins and fat soluble cholesterol from the liver to other tissues throughout the body. It is believed that the protein also carries ?TTP vitamin E neurons.

There are more than 20 mutations in the gene APTT in people with ataxia with vitamin E. Some of these mutations inhibit the synthesis of any functional protein, while other mutations change the amino acids in protein ?TTP, reducing its function. As a result, the body can not hold or use vitamin E from the diet, which results in reduced levels of this vitamin in the blood and accumulation of free radicals inside cells. Neurons in the central nervous system are particularly vulnerable to the harmful effects of free radicals and these cells die when they are deprived of vitamin E. A particular mutation APTT gene found in the Japanese population changes the amino acid histidine by amino acid glutamine at position 101 in the protein ?TTP (His101Glu or H101Q). This mutation is associated with the development of retinitis pigmentosa, an eye disorder that causes loss of vision in people with ataxia with vitamin E. Mutations in the APTT gene that inhibit protein synthesis functional ?TTP are associated with a severe form of ataxia that begins at an early age. Mutations that reduce but do not eliminate the function of the protein are associated with mild ataxia that occurs at a later age and progresses more slowly.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with ataxia with Vitamin E deficiency, by complete PCR amplification of exons APTT gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).