Ataxia with vitamin E deficiency AVED is a rare inherited neurodegenerative disorder characterized by impaired ability to coordinate voluntary movements ataxia and disease of the peripheral nervous system peripheral neuropathy.
AVED is a progressive disorder that can affect many different systems of the body multisystem disorder. Specific symptoms vary from case to case. In addition to neurological symptoms, affected individuals may experience eye abnormalities, disorders affecting the heart muscles cardiomyopathyand abnormal curvature of the spine scoliosis.
AVED is inherited as an autosomal recessive trait. Vitamin E deficiency often occurs secondary to disorders that impair the absorption of vitamin E from fat including liver disorders, wobblers syndrome and vitamin c supplementation, disorders of fat metabolism, and disorders of bile secretion. These disorders include cholestasis a syndrome of various causes characterized by impaired bile secretion ; cystic fibrosis primarily a lung wobblers syndrome and vitamin c supplementation that may also affect bile secretion ; primary biliary cirrhosis a liver disorder that results in cholestasis ; and abetalipoproteinemia a digestive disorder characterized by fat malabsorption.
Premature infants may have a low vitamin E reserve because only small amounts of vitamin E cross the placenta, and therefore they may become deficient if fed a formula high in unsaturated fats and low in vitamin E. In rare cases, vitamin E deficiency may be caused by a poor diet. For more information on the above disorders, choose the specific disorder name your search term in the Rare Disease Database.
AVED affects the central nervous system resulting in peripheral neuropathy and ataxia. Peripheral neuropathy is a general term that denotes a disorder of the peripheral nervous system. The peripheral nervous system consists of all the motor and sensory nerves that connect the brain and spinal cord to the rest of the body i.
Individuals with AVED develop progressive weakness of the legs, wobblers syndrome and vitamin c supplementation, which may appear as a staggering, lurching way of walking gait or trembling when an affected individual is standing still.
Ataxia is defined as a failure of muscle coordination that generally results in an unsteady gait. Without treatment, AVED may progress to cause significant difficulties walking and, potentially over the course of many years, can result in an affected individual becoming wheelchair bound.
Additional neurological findings include partial loss wobblers syndrome and vitamin c supplementation the sense of touch or sensitivity to pain and temperature may also occur. Wobblers syndrome and vitamin c supplementation time, reflexes in the legs may slow or be absent areflexiaand an abnormally high-arched foot pes cavus may develop with overextension hyperextension of the big toe.
Involvement of the throat muscles may lead to impaired swallowing and choking and may cause difficulty in eating. Slurred speech dysarthria may also be present.
Some affected individuals may develop a tremor or shaking of the head titubation. Intellect and emotions are rarely affected. In addition to neurological symptoms, individuals with AVED may develop symptoms affecting other systems of the body including eye abnormalities such as retinitis pigmentosa RPwhich is one name for a large group of vision disorders that cause progressive degeneration of the membrane lining the eyes retina resulting in visual impairment, wobblers syndrome and vitamin c supplementation.
Some individuals with AVED may experience a form of dystonia. Dystonia is the name for a group of movement disorders that is generally characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions postures, wobblers syndrome and vitamin c supplementation.
Genetic diseases are determined by two genes; one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. Researchers have determined that AVED results from mutations of a gene on the long arm q of chromosome 8 8q The gene regulates production of a protein alpha-tocopherol transfer protein that binds vitamin E into fatty proteins very-low-density lipoprotein or VLDL produced and secreted by the liver.
The symptoms of AVED occur because of a deficiency of vitamin E, a fat-soluble vitamin that the body needs in very small amounts. Therefore, it is not necessary to consume vitamin E daily, as long as adequate amounts are stored in the body from a well balanced diet. Vitamin E is found in various foods including vegetable oils, wheat germ, whole-grain cereals, egg yolk, and liver.
The liver stores the vitamin E-containing fat. Bile breaks down dietary fat in the small intestine so that vitamins can be absorbed.
Vitamin E is an antioxidant, a substance used by the body to protect cells from free radicals, which are atoms that are normal by-products of metabolism. Free radicals damage the cells of the body. AVED affects males and females in equal numbers, wobblers syndrome and vitamin c supplementation. The disorder is estimated to occur in fewer than 1 in 1 million people. In Tunisia, the disorder is estimated to occur in 1 inpeople.
The onset of AVED may occur during childhood or adulthood with cases reported in children as young as two and adults as old as The disorder was first described in the medical literature in Symptoms of the following disorders can be similar to those of AVED. Comparisons may be useful for a differential diagnosis:. Initial symptoms may include unsteady posture, frequent falling, wobblers syndrome and vitamin c supplementation, and progressive difficulties walking due to an impaired ability to coordinate voluntary movements ataxia.
Affected individuals may also develop abnormalities of certain reflexes; characteristic foot deformities; increasing incoordination of the arms and hands; slurred speech dysarthriaand rapid, involuntary eye movements nystagmus. Refsum syndrome is a rare disorder of lipid metabolism inherited as a recessive trait. Symptoms may include a degenerative nerve disease peripheral neuropathyfailure of muscle coordination ataxiaretinitis pigmentosa a progressive vision disorderand bone and skin changes.
This wobblers syndrome and vitamin c supplementation is believed to be due to the absence of phytanic acid hydroxylase in the blood, an enzyme needed for the metabolism of phytanic acid found in dairy products, beef, lamb and some seafoods.
Refsum syndrome is characterized by a marked accumulation of phytanic acid in the plasma and tissues. Prolonged treatment with a diet deficient in phytanic acid can be beneficial.
This slowly progressive disorder is most common in children and young adults of Scandinavian heritage. Phytanic acid is a derivative of phytol, a component of chlorophyll. Abetalipoproteinemia is a rare inherited disorder of fat metabolism. Abnormalities in fat metabolism result in malabsorption of dietary fat and vitamin E. Affected individuals experience progressive neurological deterioration, muscle weakness, difficulty waling and blood abnormalities including a condition where the red blood cells are malformed acanthocytosis resulting in low levels of circulating red blood cells anemia.
Affected individuals may also develop degeneration of the retina of the eyes potentially resulting in loss of vision retinitis pigmentosa. Abetalipoproteinemia is inherited as an autosomal recessive trait. The following disorders may be associated with AVED as secondary characteristics. They are not necessary for a differential diagnosis: For more information on these conditions, choose the specific name as your search term in the Rare Disease Database.
A diagnosis of AVED is made based upon a thorough clinical evaluation, a detailed patient history and a variety of tests and characteristic findings e. Vitamin E treatment has often halted the progression of the disorder and, in some cases, improved existing neurological symptoms. Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
Information on current clinical trials is posted on the Internet at www. All studies receiving U. Wobblers syndrome and vitamin c supplementation note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder e.
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Myoclonic dystonia as unique presentation of isolated vitamin E deficiency in a young patient. Benomar A, et al. Feki M, et al. Etiopathogenesis, clinical, histopathologic, and electrical features, and main etiologies. Gabsi S, et al. Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency. Alex G, et al. Ataxia with isolated vitamin E deficiency: J Paediatr Child Health. Martinello F, et al. Supplemental therapy in isolated vitamin E deficiency improves the peripheral neuropathy and prevents the progression of ataxia, wobblers syndrome and vitamin c supplementation.
Cavalier L, et al. Am J Hum Genet. Yokota T, et al. Friedreich-like ataxia with retinitis pigmentosa caused by the HisGln mutation of the alpha-tocopherol transfer protein gene. Ben Hamida M, et al. Ben Hamida C, et al. Localization of Friedreich ataxia phenotype with selective vitamin E deficiency to chromosome 8q sugarloaf house plan and pictures homozygosity mapping. Trager MG, et al. Impaired ability of patients with familial isolated vitamin E deficiency to incorporate alpha-tocopheral into lipoproteins secreted by the liver.