The most important factor influencing the response to treatment is the duration of symptoms; age, sex, and the degree of anemia are of lesser importance. The greatest improvements occur in patients whose disturbance of gait has been present for less than 3 months and recovery is usually complete if therapy is instituted within a few weeks after the onset of symptoms. All neurologic symptoms and signs may improve, mostly during the first 3 to 6 months of therapy, and then at a slower tempo during the ensuing year or even longer. In practically all instances, there is some degree of improvement after treatment, although in cases of longest duration, the best that can be accomplished is an arrest of progression.
This occurs in 2 types: a defect in intestinal absorption and an inherent hepatic enzyme deficiency that blocks incorporation of vitamin E into lipoprotein. A rare neurologic disorder of childhood, sometimes later in life, consisting essentially of spinocerebellar degeneration in association with polyneuropathy and pigmentary retinopathy, has been attributed to a deficiency of vitamin E consequent to prolonged intestinal fat malabsorption (Muller et al;
Satya-Murti et al). The same mechanism has been proposed to explain the neurologic disorders that sometimes complicate abetalipoproteinemia (see Chap. 36), fibrocystic disease (Sokol et al), celiac sprue disease, and extensive intestinal resections, intrinsic bowel syndromes, or cholestatic liver disease that cause malabsorption, even decades after the onset of surgery or of the medical disorder (Harding et al). Vitamin E deficiency has also been observed in young children with chronic cholestatic hepatobiliary disease (Rosenblum et al).
Ataxia, loss of tendon reflexes, ophthalmoparesis, proximal muscle weakness with elevated serum creatine kinase, and decreased sensation are the usual manifestations of vitamin E deficiency. These symptoms are referable to parts of the nervous system and musculature that are found to be diseased in animals deprived of vitamin E: degeneration of Clark columns, spinocerebellar tracts, posterior columns, nuclei of Goll and Burdach, and sensory roots (Nelson et al). Local differences in the natural concentration of vitamin E in various parts of the nervous system and musculature are believed to account for the distribution of the lesions. In affected children, neurologic function improves after long-term daily supplementation with high doses of vitamin E.
In addition to abetalipoproteinemia, there exists a form of spinocerebellar degeneration attributable to an inherited but conditioned deficiency of vitamin E that may closely mimic the phenotype of Friedreich ataxia (“familial isolated vitamin E deficiency” as discussed in Chap. 38). The onset is usually in early adolescence, but there is variability, particularly among different families. In these patients, absorption and transport of vitamin E to the liver is normal, but hepatic incorporation of tocopherol (the active form of vitamin E) into very-low-density lipoproteins is defective (Traber et al). The abnormality has been traced to a mutation in TTPA, the gene encoding α-tocopherol transfer protein (Gotoda et al). In a sense, this is a vitamin deficiency conditioned by a genetic mutation. The mutations and clinical manifestations have been variable, as pointed out in a study of 41 patients in 27 families carried out by Cavalier and colleagues. The age of onset ranged from 2 to 52 year, but generally before age 20. Unexpected features such as head titubation and dystonia occurred in some cases but unlike Friedreich ataxia, cardiomyopathy was rare. An important feature of these cases is that chronic oral administration of large doses of vitamin E can halt and even reverse progression of the ataxia (Gabsi et al).