Vitamin E Deficiency

Pathogenesis

The term vitamin E denotes a group of 8 compounds with similar structures and antioxidant activity. The most potent member of these compounds is α-tocopherol , which is also the main form in humans. The best dietary sources of vitamin E are vegetable oils, seeds, nuts, green leafy vegetables, and margarine (see Table 64.1 ).

The majority of vitamin E is located within cell membranes, where it prevents lipid peroxidation and the formation of free radicals. Other antioxidants, such as ascorbic acid, enhance the antioxidant activity of vitamin E. The importance of other functions of vitamin E is still being delineated.

Premature infants are particularly susceptible to vitamin E deficiency, because there is significant transfer of vitamin E during the last trimester of pregnancy. Vitamin E deficiency in premature infants causes thrombocytosis, edema, and hemolysis, potentially causing anemia. The risk of symptomatic vitamin E deficiency was increased by the use of formulas for premature infants that had a high content of polyunsaturated fatty acids (PUFAs). These formulas led to a high content of PUFAs in red blood cell membranes, making them more susceptible to oxidative stress, which could be ameliorated by vitamin E. Oxidative stress was augmented by aggressive use of iron supplementation; iron increases the production of oxygen radicals. The incidence of hemolysis as a result of vitamin E deficiency in premature infants decreased secondary to the use of formulas with a lower content of PUFAs, less-aggressive use of iron, and provision of adequate vitamin E.

Because vitamin E is plentiful in common foods, primary dietary deficiency is rare except in premature infants and in severe, generalized malnutrition. Vitamin E deficiency does occur in children with fat malabsorption secondary to the bile acid needed for vitamin E absorption. Although symptomatic disease is most common in children with cholestatic liver disease, it can occur in patients with cystic fibrosis, celiac disease, short bowel syndrome, and Crohn disease. The autosomal recessive disorder abetalipoproteinemia causes fat malabsorption, and vitamin E deficiency is a common complication (see Chapter 104 ).

In ataxia with isolated vitamin E deficiency (AVED) , a rare autosomal recessive disorder, there are mutations in the gene for α-tocopherol transfer protein ( TTPA ). Patients with this disorder are unable to incorporate vitamin E into lipoproteins before their release from the liver, leading to reduced serum levels of vitamin E. There is no associated fat malabsorption, and absorption of vitamin E from the intestine occurs normally.

Clinical Manifestations

A severe, progressive neurologic disorder occurs in patients with prolonged vitamin E deficiency. Clinical manifestations do not appear until after 1 yr of age, even in children with cholestasis since birth. Patients may have cerebellar disease, posterior column dysfunction, and retinal disease. Loss of deep tendon reflexes is usually the initial finding. Subsequent manifestations include limb ataxia (intention tremor, dysdiadochokinesia), truncal ataxia (wide-based, unsteady gait), dysarthria, ophthalmoplegia (limited upward gaze), nystagmus, decreased proprioception (positive Romberg test), decreased vibratory sensation, and dysarthria. Some patients have pigmentary retinopathy. Visual field constriction can progress to blindness. Cognition and behavior can also be affected. Myopathy and cardiac arrhythmias are less common findings.

In premature infants, hemolysis as a result of vitamin E deficiency typically develops during the 2nd mo of life. Edema may also be present.