Vitamin E

Overview

• Fat soluble vitamin
• Antioxidant function
• Vitamin E denotes 8 different compounds
• most potent/main form in humans = alpha tocopherol

Clinical Manifestations  (do not appear until after 1 year of age)

• Severe progressive neurological disorder with prolonged deficiency
• loss of deep tendon reflexes -usually the initial finding
• limb ataxia (intention tremor, dysdiadochokinesia)
• truncal ataxia (wide-based, unsteady gait)
• dysarthria
• ophthalmoplegia (limited upward gaze)
  
• nystagmus
  
• decreased proprioception (positive romberg test)
• descreased vibratory sensation
• +/- pigmentary retinopathy
• Visual field constriction can progress to blindness
• Congnition and behavior can be affected
• myopathy and cardiac arrhythmias less common
• cerebellar disease
• posterior column dysfunction
• retinal disease
  
• Premature infants
• hemolysis during 2nd month of life
• +/- edema
• Altered prostaglandin synthesis
  

Diagnosis

• Serum Vit E levels increase with high serum lipid levels. (even in deficient states)
• Use ratio of vit E to serum lipids

• Ratio of Vitamin E to Serum Lipids	Abnormal value in this age group
  <0.8 mg/g	Older children and adults
  <0.6 mg/g	Infants <1yr

  
  

• Premature infants with hemolysis caused by Vitamin E deficiency also have elevated platelets
• Somatosensory evoked potentials and nerve conduction studies may reveal neurological abnormalities
• Electroretinography can reveal abnormalities before physical exam findings are present if patient has retinal involvement
  

DDx

• Premature infants with unexplained hemolytic anemia after the 1st mo (esp if thrombocytosis present) should be empirically treated with Vitamin E or have Vit E/Serum lipid ratio measured
• Children with Neurological findings and a disease that causes fat malabsorption should have vitamin E status evaluated
• Ataxia with Vitamin E deficiency (AVED) will not have symptoms of malabsorption and may be misdiagnosed as Fredreich ataxia.
• Unexplained Ataxia should be screened for Vit E deficiency

Tx

• Group	Dose	Notes
  Neonates	25-50 Units/day for 1 wk	follow with adequate dietary intake
  Children w/ malabsorption	1 Unit/kg/d	adjust dose based on levels
  AVED	high dose	ongoing treatment required

  
  
• hemolytic anemia in infants resolves with vit E correction
  
• Some neuro Sx may be reversible with early treatment - but many have little improvment; however, treatment does prevent progression

Dietary Sources

• Vegetable oils
• margerine
• wheat germ
• nuts
• green leafy vegetables
  

Biomechanics

• Absorbed in Jejunum (nonsaturable passive diffusion)
• Most Vitamin E is located within cell membranes
• Vitamin E prevents lipid peroxidation preventing the formation of free radicals.
  
• Vitamin E donates an electron to a lipid peroxy radical, it is converted to a free radical form that is stabilized by resonance (Marks Basic Medical Biochemistry, 2nd Ed). It will actually dontate an electron and become a free radical itself but then it will preferentially donate a second electron to become the stable tocopherol quinone thus terminating the free radical chain reaction.
  
• Ascorbic acid enhances the antioxidant activity of Vitamin E
• Other functions of Vitamin E are still under investigation
• Neuro Sx are thought to occur in Vit E deficiency due to the inability to prevent free radical formation. polyunsaturated lipids in myelin and other membranes of CNS/PNS are particularly susceptible to free radical injury. Vitamin E circulates in the blood in lipoprotein molecules
  
• Premature Infants
• Most Vitamin E is transferred from mother to fetus in the last trimester
• Prematurity increased risk of deficiency
• Risk is increased with the use of formulas containing a high content of polyunsaturated fatty acids (PUFAs) - PUFAs enter RBC membrane and increase oxidative stress. Iron supplementation augments this stress and produces oxygen free radicals --> hemolysis
  
• Vit E Deficiency causes:
• thrombocytosis
• edema
• hemolysis
• anemia
• Because Vitamin E is plentiful in foods primary dietary deficiency is rare except in premature infants and severe generalized malnutrition
• Fat malabsorption can produce vit E deficiency as well because the bile acid is needed for Vit E absorption
• Cholestatic liver disease (most common player)
  
• Cystic fibrosis
• Celiac disease
• Short bowel syndrome
• Crohn disease
• Abetalipoproteinemia (autosomal recessive) -causes fat malabsorption and Vit E deficiency is common
• Ataxia with isolated Vitamin E deficiency (AVED) - rare autosomal recessive disorder
• mutations in the gene for alpha tocopherol transfer protein
• patients cannot incorporate Vit E into lipoproteins before their release from the liver
• In this case there is no associated fat malabsoption, Vit E is absorbed from the intestine

• Impairment of neutrophil function
• Coagulopathy
• Thrombocytopenia
• Cerebral hemorrhages
  

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2. Tortora, Gerard J. Principles of Anatomy and Physiology. 15th ed. Hoboken, NJ: J. Wiley, 2009. Print.
3. Moore, Keith L.,, Arthur F. Dalley, II, and Keith L Moore. Clinically Oriented Anatomy. Fifth edition. Baltimore: Wolters Kluwer Health, 2009. Print.
4. Kleinman RE, Goulet O, Mieli-Vergani G, et al, eds. Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, and Management. 5th ed. Hamilton, Ontario: BC Decker; 2008.
5. The NASPGHAN fellows concise review of pediatric gastroenterology, hepatology, and nutrition. 1st edition (2011)
6. Wyllie, Robert & Hyams, J.S.. (2011). Pediatric Gastrointestinal and Liver Disease. 10.1016/C2009-0-53242-4.  (Accessed online Feb 2020)
7. Coran, Arnold G, and N S. Adzick. Pediatric Surgery. Philadelphia, PA: Elsevier Mosby, 2012. Internet resource.