History

Fact Explanation
Muscle weakness Vitamin E is a fat-soluble vitamin. Alfa tocoferol is the most active form of vitamin E. [1] It is important to the human body as an antioxidant and free-radical scavenger in lipophilic environments. Absorption, is bile dependent and then it is stored in adipose tissue, liver, and muscle.
Poor dietary hobbits and malnutrition Malnutrition is associated with deficiency of protein, calorie, vitamin and mineral deficiencies. Associated deficiency states of vitamins A, D, E, and K which needs appropriate supplementation. [1] Spinach, nuts, sunflower seeds, avocados, fish, shellfish, plant oils are the food that are rich in vitamin E.
Problems with walking Gait abnormalities such as ataxia may occur. [4]
Visual problems Ophthalmoplegia, may occur initially leading to blindness at later stages. [4]
Abnormalities in stool consistancy Steatorrhoea is the passage of greasy stools which are difficult to flush. This usually occur in fat malabsorption. [1]
History of cystic fibrosis, caeliac disease, betalipoproteinemia, intesianal lymphangectasia, chronic cholestatic hepatobiliary disease Absorption of vitamin E is mediated by bile. Therefore any impairment of biliary secretion or normal pancreatic biliary function will affects the absorption of vitamin E. [2]
History of bowel surgery Surgical resection will shorten the bowel leading to impaired absorption. [2]
Pale stools, dark urine, failure to thrive [3] These may be the features of biliary atresia. [3]
References
  1. FARRELL PM, BIERI JG, FRATANTONI JF, WOOD RE, DI SANT'AGNESE PA. The Occurrence and Effects of Human Vitamin E Deficiency: A STUDY IN PATIENTS WITH CYSTIC FIBROSIS J Clin Invest [online] 1977 Jul, 60(1):233-241 [viewed 28 August 2014] Available from: doi:10.1172/JCI108760
  2. LOSOWSKY MS, LEONARD PJ. Evidence of vitamin E deficiency in patients with malabsorption or alcoholism and the effects of therapy. Gut [online] 1967 Dec, 8(6):539-543 [viewed 19 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1552745
  3. KELLY DA, DAVENPORT M. Current management of biliary atresia Arch Dis Child [online] 2007 Dec, 92(12):1132-1135 [viewed 28 August 2014] Available from: doi:10.1136/adc.2006.101451
  4. RIZVI S, RAZA ST, AHMED F, AHMAD A, ABBAS S, MAHDI F. The Role of Vitamin E in Human Health and Some Diseases Sultan Qaboos Univ Med J [online] 2014 May, 14(2):e157-e165 [viewed 19 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997530

Examination

Fact Explanation
Abnormal neurological examination:-hyporeflexia, decreased proprioception, decreased vibratory sense, distal muscle weakness These are early signs of vitamin E deficiency. Muscle weakness [2] may be more in distal areas of the limbs.
Visual problems Opthalmoplegia initially occurs and may progress to total blindness [3] with continued deficiency.
Gait abnormalities:- truncal and limb ataxia, nystagmus Late signs of advanced disease. [4] Nystagmus may be upward gaze or dissociated.
Dysphagia and dysarthria May be evident at a latter stage due to muscle weakness. [1]
Irregular pulse Cardiac arrhythmias, will occur with continued deficiency of vitamin E. [6]
Impaired cognition and memory loss Later stages of the disease will have these features. Memory loss may progress to the dementia. [5]
Hepatomegaly, Splenomegaly Due to associated cholestatic disease. [1]
References
  1. KELLY DA, DAVENPORT M. Current management of biliary atresia Arch Dis Child [online] 2007 Dec, 92(12):1132-1135 [viewed 28 August 2014] Available from: doi:10.1136/adc.2006.101451
  2. FARRELL PM, BIERI JG, FRATANTONI JF, WOOD RE, DI SANT'AGNESE PA. The Occurrence and Effects of Human Vitamin E Deficiency: A STUDY IN PATIENTS WITH CYSTIC FIBROSIS J Clin Invest [online] 1977 Jul, 60(1):233-241 [viewed 28 August 2014] Available from: doi:10.1172/JCI108760
  3. RAHI JS, SRIPATHI S, GILBERT CE, FOSTER A. Childhood blindness due to vitamin A deficiency in India: regional variations. Arch Dis Child [online] 1995 Apr, 72(4):330-333 [viewed 19 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1511233
  4. SARIS NE. [Reliability of doping tests in sports]. Duodecim [online] 1975, 91(11):687-9 [viewed 19 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/1241
  5. LLEWELLYN DJ, LANG IA, LANGA KM, MELZER D. Vitamin D and Cognitive Impairment in the Elderly U.S. Population J Gerontol A Biol Sci Med Sci [online] 2011 Jan, 66A(1):59-65 [viewed 19 September 2014] Available from: doi:10.1093/gerona/glq185
  6. ALSHAHRANI F, ALJOHANI N. Vitamin D: Deficiency, Sufficiency and Toxicity Nutrients [online] , 5(9):3605-3616 [viewed 19 September 2014] Available from: doi:10.3390/nu5093605

Differential Diagnoses

Fact Explanation
Biliary Disease Cholestasis due to various reasons may predisposes to fat-soluble vitamin (FSV) deficiencies. [2] Biliary atresia is one such condition that results in vitamin E deficiency specially in infants and young children.There is an obstruction of the extrahepatic biliary tree leading to decreased bile flow. They will have features of chronic liver disease as well. Treatment is by surgical hepatoportoenterostomy (HPE) to restores bile flow. Other diseases causing cholestatic liver disease are primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune cholangiopathy. [3]
Neurological disorders Abnormal neurological examination is present in advanced state of vitamin E deficiency manifesting as hyporeflexia, decreased proprioception, decreased vibratory sense and muscle weakness. Muscle weakness may be more distal in this condition making it different from other proximal myopathies. Other causes of distal myopathy include welander (Late onset type I) distal myopathy, late onset type IIa; Udd) distal myopathy, markesbery (late adult onset type IIb) distal myopathy, and hereditary inclusion body myopathy. On the other hand as these are inherited by an autosomal dominant or recessive pattern, they might have a family history. [1]
References
  1. LAING NG, LAING BA, MEREDITH C, WILTON SD, ROBBINS P, HONEYMAN K, DOROSZ S, KOZMAN H, MASTAGLIA FL, KAKULAS BA. Autosomal dominant distal myopathy: linkage to chromosome 14. Am J Hum Genet [online] 1995 Feb, 56(2):422-427 [viewed 28 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1801149
  2. KOWDLEY KRIS V.. LIPIDS AND LIPID-ACTIVATED VITAMINS IN CHRONIC CHOLESTATIC DISEASES. Clinics in Liver Disease [online] 1998 May, 2(2):373-389 [viewed 28 August 2014] Available from: doi:10.1016/S1089-3261(05)70013-1

Investigations - for Diagnosis

Fact Explanation
Vitamin E/alpha-tocopherol level plasma level Usually reduced in an deficiency. [1] Usual reference range of vitamin E in adults is 5.5-17 µg/mL and in children, it is 3-18.4 µg/mL. There can be overestimation of the level of vitamin E by 10-20% in this measurement. [2]
Urinary creatinine levels Vitamin E deficiency is associated with excess creatinine excretion in urine. [1]
References
  1. LOSOWSKY MS, LEONARD PJ. Evidence of vitamin E deficiency in patients with malabsorption or alcoholism and the effects of therapy. Gut [online] 1967 Dec, 8(6):539-543 [viewed 28 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1552745
  2. FARRELL PM, BIERI JG, FRATANTONI JF, WOOD RE, DI SANT'AGNESE PA. The Occurrence and Effects of Human Vitamin E Deficiency: A STUDY IN PATIENTS WITH CYSTIC FIBROSIS J Clin Invest [online] 1977 Jul, 60(1):233-241 [viewed 28 August 2014] Available from: doi:10.1172/JCI108760

Investigations - Fitness for Management

Fact Explanation
Haemoglobin level There can be haemolysis of red blood cells on exposure to the hydrogen peroxide due to the vitamin E deficiency. [1]
Reticulocyte count Will be below the normal range. [1]
Red cell survival May be decreased due to haemolysis. This is done by assessing the half life of using 51 Cr labelled red blood cells. [2]
References
  1. LOSOWSKY MS, LEONARD PJ. Evidence of vitamin E deficiency in patients with malabsorption or alcoholism and the effects of therapy. Gut [online] 1967 Dec, 8(6):539-543 [viewed 28 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1552745
  2. FARRELL PM, BIERI JG, FRATANTONI JF, WOOD RE, DI SANT'AGNESE PA. The Occurrence and Effects of Human Vitamin E Deficiency: A STUDY IN PATIENTS WITH CYSTIC FIBROSIS J Clin Invest [online] 1977 Jul, 60(1):233-241 [viewed 28 August 2014] Available from: doi:10.1172/JCI108760

Investigations - Followup

Fact Explanation
Serum level of vitamin E Patients, at risk of deficiency needs to undergo regular assessment of the serum vitamin E levels. [1] With the treatment plasma levels will come back to normal.
References
  1. LOSOWSKY MS, LEONARD PJ. Evidence of vitamin E deficiency in patients with malabsorption or alcoholism and the effects of therapy. Gut [online] 1967 Dec, 8(6):539-543 [viewed 28 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1552745

Investigations - Screening/Staging

Fact Explanation
Electrocardiogram Cardiac arrhythmias are a potential complication at an latter stage. [1]
Electromyogram (EMG) To evaluate the muscle weakness in vitamin E deficency. [3]
Faecal fat output May be increased in cases of fat mal absorption. [2]
References
  1. LOSOWSKY MS, LEONARD PJ. Evidence of vitamin E deficiency in patients with malabsorption or alcoholism and the effects of therapy. Gut [online] 1967 Dec, 8(6):539-543 [viewed 28 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1552745
  2. HASAN FM, KAZEMI H. Dual contribution theory of regulation of CSF HCO3 in respiratory acidosis. J Appl Physiol [online] 1976 Apr, 40(4):559-67 [viewed 19 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/6420
  3. RIZVI S, RAZA ST, AHMED F, AHMAD A, ABBAS S, MAHDI F. The Role of Vitamin E in Human Health and Some Diseases Sultan Qaboos Univ Med J [online] 2014 May, 14(2):e157-e165 [viewed 19 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997530

Management - General Measures

Fact Explanation
Prevention in high risk groups After surgical treatment, for biliary atresia it is advised to administer vitamin supplementation to prevent biochemical and clinical deficiency states of vitamins A, D, E, and K. [1] Recomended doses may vary according to the disease condition
Nutrition Advice should be given on having a diet rich in essential vitamins. Spinach, nuts, sunflower seeds, avocados, fish, shellfish, plant oils are the food that are rich in vitamin E.
Treat the associated vitamin deficiencies In conditions with fat soluble vitamin deficiency, there can be associated deficiency states of vitamins A, D, E, and K which needs appropriate supplementation. [1]
Management of complications Complications like cardiac arrhythmias, limb weakness, visual problems may need specific management.
References
  1. SHNEIDER BL, MAGEE JC, BEZERRA JA, HABER B, KARPEN SJ, RAGHUNATHAN T, ROSENTHAL P, SCHWARZ K, SUCHY FJ, KERKAR N, TURMELLE Y, WHITINGTON PF, ROBUCK PR, SOKOL RJ. Efficacy of Fat-Soluble Vitamin Supplementation in Infants With Biliary Atresia Pediatrics [online] 2012 Sep, 130(3):e607-e614 [viewed 28 August 2014] Available from: doi:10.1542/peds.2011-1423

Management - Specific Treatments

Fact Explanation
Supplementation of vitamin E Fat-soluble vitamins (FSVs) supplementation to provide vitaminsis done in deficient states. It is given either orally or intramuscularly. Usually high doses are required in individual vitamin supplimentaion. A liquid multiple FSV preparation made with d-α tocopheryl polyethylene glycol-1000 succinate is usually used. [1] Vitamin E overdose is extremely uncommon.
Use of multiple vitamin preparations This is another way of supplying deficient vitamins specially in a case of multiple vitamin deficiency as in cholestatic liver disease. [1] People with total bilirubin at or above 2 mg/dL remain at high risk for fat soluble vitamin insufficiency and thus needs supplements with additional vitamin K. Development of more effective multiple vitamin supplements for childhood cholestasis is
References
  1. SHNEIDER BL, MAGEE JC, BEZERRA JA, HABER B, KARPEN SJ, RAGHUNATHAN T, ROSENTHAL P, SCHWARZ K, SUCHY FJ, KERKAR N, TURMELLE Y, WHITINGTON PF, ROBUCK PR, SOKOL RJ. Efficacy of Fat-Soluble Vitamin Supplementation in Infants With Biliary Atresia Pediatrics [online] 2012 Sep, 130(3):e607-e614 [viewed 28 August 2014] Available from: doi:10.1542/peds.2011-1423