Neurological deficits may include hyporeflexia, ataxia, strabismus, limitations in upward gaze, but also constriction of the visual field and profound muscle weakness [5]. Dysarthria, absence of deep tendon reflexes, loss of vibratory sensations and positive Babinski reflexes may also be encountered in vitamin E deficient individuals [2]. In most severe cases, blindness, dementia, irreversible nerve damage and cardiac arrhythmias can develop [2] [5].

• Weakness

  Affected patients may develop spinocerebellar degeneration with dysarthria, ataxia, proximal weakness, proprioceptive loss and areflexia. [ncbi.nlm.nih.gov]

  Vitamin E deficiency may cause impaired reflexes and coordination, difficulty walking, and weak muscles. Premature infants with the deficiency may develop a serious form of anemia. [merckmanuals.com]

• Asymptomatic

  This case documents a potentially reversible visual evoked potential abnormality in a visually asymptomatic patient with vitamin E deficiency. [ncbi.nlm.nih.gov]

  Early deficiency was generally asymptomatic, and intermediate deficiency produced some impairment. Ataxia, weakness, reflex changes, impaired vision, and pigment retinopathy were associated with chronic, advanced deficiency. [neurology.org]

  Two presymptomatic siblings on supplementation remained asymptomatic. Two patients, one on therapy for 15 months 10 and one for seven months, 11 showed minor improvement. [jnnp.bmj.com]

  L., Atger, V., Simon, A., Moatti, N. ( 1998 ) Erythrocyte antioxidant status in asymptomatic hypercholesterolemic men. Atherosclerosis 138 ,375-381 Crossref Medline, Google Scholar 51 Traber, M. [fasebj.org]

• Malnutrition

  Three infants are described with cystic fibrosis (CF) and malnutrition leading to severe anemia beginning as early as 6 weeks of age. [ncbi.nlm.nih.gov]

  Anyone suffering from malnutrition Adults following extremely low fat diets People more than 55 years old Anyone with liver, pancreatic or gallbladder disease Anyone under excess stress for a prolonged period of time If you have experienced recent injuries [vitamins.lovetoknow.com]

  Individuals most at-risk for vitamin E deficiency include: elderly adults, premature and/or underweight infants, those with abnormal fat absorption, people on very low-fat diets, and those with any type of malnutrition. 8 Signs You Have A Vitamin E Deficiency [powerofpositivity.com]

  "Cognitive Function of Children with Cystic Fibrosis: Deleterious Effect of Early Malnutrition." Pediatrics 113 (June 2004): 1549-1558. Laso, N., S. Mas, M. Jose Lafuente, et al. [medical-dictionary.thefreedictionary.com]

• Difficulty Walking

  Vitamin E deficiency may cause impaired reflexes and coordination, difficulty walking, and weak muscles. Premature infants with the deficiency may develop a serious form of anemia. [merckmanuals.com]

  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. [rarediseases.org]

• Nausea

  […] dietary intake of vitamin E prescribed vitamin E therapy, including drug names, dosages, frequency and schedule of administration, and duration of therapy possible adverse effects of vitamin E therapy, including muscle weakness, fatigue, headaches, nausea [quizlet.com]

  Possible vitamin E side effects include nausea, diarrhea, stomach cramps, fatigue, headache, blurred vision and rash [13]. Toxic effects of vitamin E has not been observed so far [10]. [nutrientsreview.com]

  Women who took vitamin E supplements during their first eight weeks of pregnancy showed an increase of congenital heart defects. ( 15 ) High doses of vitamin E can also sometimes lead to nausea, diarrhea, stomach cramps, fatigue, weakness, headache, blurred [draxe.com]

• Muscle Weakness

  The most prominent clinical features were abnormal eye movements, diminished reflexes, decreased vibratory and position sense, ataxia, and muscle weakness. [ncbi.nlm.nih.gov]

  Affected premature neonates have muscle weakness. [merckmanuals.com]

• Retinal Pigmentation

  Some affected individuals may experience vision loss due to damage to the back of the eye ( retinitis pigmentosa ). [rarediseases.info.nih.gov]

• Ataxia

  Abstract Ataxia with vitamin E deficiency is an autosomal recessive condition associated with a defect in the a-tocopherol transfer protein. Clinically it manifests as a progressive ataxia with a phenotype resembling that of Friedreich's ataxia. [ncbi.nlm.nih.gov]

• Areflexia

  A progressive neurological disorder comprising ataxia, areflexia, and loss of proprioception developed in their sixth and seventh decades. [ncbi.nlm.nih.gov]

• Cerebellar Ataxia

  Abstract Ataxia with vitamin E deficiency is an autosomal recessive cerebellar ataxia caused by mutations in the α-tocopherol transfer protein coding gene localized on chromosome 8q, leading to lower levels of serum vitamin E. [ncbi.nlm.nih.gov]

  Other autosomal recessive cerebellar ataxias may be considered as well (Refsum disease, ataxia telangiectasia, Charcot-Marie-Tooth disease 1A and ataxia with oculomotor apraxia types 1 and 2 (see these terms)). [orpha.net]

• Hyporeflexia

  One child, 11 years of age, had severe hyporeflexia and decreased vibratory sense. Nerve conduction was delayed. The second child, 2 years of age, was neurologically normal. [ncbi.nlm.nih.gov]

  Abnormalities relating vitamin E deficiency progress from hyporeflexia, ataxia, limitation in upward gaze, and strabismus to long-tract defects, including visual-field constriction and profound muscle weakness. [4] Complete blindness, cardiac arrhythmia [emedicine.medscape.com]

• Neurologic Manifestation

  A gluten-free diet and vitamin E supplementation reversed both the clinical neurological manifestations and the abnormalities in the muscle biopsy. Anti-gliadin antibodies were no longer present. [ncbi.nlm.nih.gov]

  In abetalipoproteinemia, retinopathy and neurologic manifestations may be prevented by vitamin E supplementation (1). In infants with very low birthweight, vitamin E deficiency may present as hemolytic anemia and edema (2). [annals.org]

  manifestation, 054078, 症状, ｼｮｳｼﾞｮｳ, symptom, 040039, 神経系疾患, ｼﾝｹｲｹｲｼｯｶﾝ, nervous system disease, 023401, 酸素複素環化合物, ｻﾝｿﾌｸｿｶﾝｶｺﾞｳﾌﾞﾂ, oxygen heterocyclic compound, 022640, 複素環化合物, ﾌｸｿｶﾝｶｺﾞｳﾌﾞﾂ, heterocyclic compound, 036132, 脂溶性ビタミン, ｼﾖｳｾｲﾋﾞﾀﾐﾝ, fat-soluble [togodb.biosciencedbc.jp]

  Discussion Secondary vitamin E deficiency (precipitated by abetalipoproteinaemia or other fat malabsorptive states) is known to be associated with neurological manifestations including ataxia. [jnnp.bmj.com]

A thorough neurological examination to assess the extent of symptoms is vital in the diagnostic workup [5], but to confirm vitamin E deficiency, serum levels of α-tocopherol should be determined and values of < 5 µg/mL (or < 11.6 µmol/L) are diagnostic for this hypovitaminosis [4]. A lipid profile should also be obtained and a reduced α-tocopherol to lipid ration can also provide an accurate diagnosis. The search for an underlying cause should start with a thorough abdominal examination through ultrasonography or more invasive procedures (such as endoscopy) if there is valid clinical suspicion toward fat malabsorption [4].

Supplementation of α-tocopherol, either in oral or parenteral formulations, is the mainstay of treatment [5] [6]. A dose of 15-25 mg/kg is given every day in the setting of oral supplementation, while parenteral dosages may be higher in order to overcome the inability to utilize vitamin E from the gut [4].

Early recognition of the disease carries a good prognosis, but profound nerve damage may be irreversible without timely identification of the underlying cause and appropriate treatment.

Various diseases have shown to induce vitamin E deficiency. Abetalipoproteinemia, chronic cholestatic liver disease, pancreatitis, short bowel syndrome, but also cystic fibrosis may cause fat malabsorption in the gut and thus impair normal vitamin E utilization from the gastrointestinal tract [4] [5].

The exact rates of vitamin E deficiency in the world are unknown, but isolated reports showed that more than 50% of individuals in Thailand suffer from this hypovitaminosis [6]. Additionally, it is estimated that more than 90% of individuals living in the United States do not meet the recommended dietary intake of vitamin E (15 mg/day) [1], suggesting that the issue of insufficient ingestion of vitamin E is on a global scale.

α-tocopherol is one of the most potent free radical scavengers in the human body and it is absorbed from the gastrointestinal tract as a fat-soluble vitamin [4]. Under physiological conditions, vitamin E is the primary defense against lipid peroxidation that can cause severe damage to cell membranes and neurons [7]. In its absence, fragility of red blood cells and degeneration of neurons is the main cause of symptom development [4].

Ensuring sufficient dietary intake is an effective preventive strategy. Edible oils are abundant with vitamin E and the the richest source of this nutrient, whereas almonds, hazelnuts, peanuts, spinach, broccoli, mango and tomato are also sources of α-tocopherol [2].

Vitamin E is a lipid-soluble vitamin considered to be one of the most important antioxidant nutrients in the body, as it prevents cell membrane lipid peroxidation [1]. The form which is considered to be most active, α-tocopherol, acts as a peroxyl radical scavenger in lipid environments and possesses numerous beneficiary roles in the body, including prevention of oxidative stress, but also regulation of platelet aggregation, protein kinase C activation and preservation of the cardiovascular and immune systems [1] [2]. Its deficiency can stem from inadequate dietary intake, the most common cause in the developed world, or from gastric surgery and diseases that induce fat malabsorption (cystic fibrosis, abetalipoproteinemia) [3] [4]. Hemolytic anemia and a myriad of neurological symptoms (due to neuronal death induced by free radicals that are not scavenged by α-tocopherol) are principal symptoms and the diagnosis can be made by determining levels of α-tocopherol in blood together with serum lipids [2] [4]. Vitamin E supplementation and diet correction (when possible) are two main methods of treatment [2].

Vitamin E deficiency is a condition that stems either from inadequate dietary intake or due to diseases that impede its absorption from the gastrointestinal tract, such as abetalipoproteinemia, cholestatic liver disease, cystic fibrosis, short bowel syndrome or cystic fibrosis. Vitamin E, in its most biologically active form, α-tocopherol, is an essential part of defense against free radicals that can cause cell membrane damage and in its absence, the neurons and the red blood cells are most severely affected, leading to anemia and various neurological symptoms. Attenuated reflexes, visual deficits, muscle weakness, difficulties with speech and dementia are some of the most common symptoms, whereas severe deficiencies can lead to blindness and cardiac arrhythmias. To diagnose vitamin E deficiency, it is necessary to measure its concentrations in blood and to obtain a full lipid profile. Treatment comprises supplementation with vitamin E, either through tablets or injections, depending on the underlying cause. Many studies have concluded that inadequate dietary intake of vitamin E is a global issue, which is why vitamin E-rich foods - edible oils, almonds, hazelnuts, peanuts, spinach and broccoli must be taken on a regular basis.

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