α-tocopherol concentrations, including those in the nervous tissues (Burton et al., 1998). Importantly, the lower dose, even though given for more than a year and a half, did not increase tissue tocopherol concentrations.

Vitamin E deficiency occurs only rarely in humans, and overt deficiency symptoms in normal individuals consuming diets low in vitamin E have never been described. Vitamin E deficiency occurs only as a result of genetic abnormalities in α-TTP, as a result of various fat malabsorption syndromes (Rader and Brewer, 1993; Sokol, 1993), or as a result of protein-energy malnutrition (Kalra et al., 1998; Laditan and Ette, 1982).

Only a handful of families with clinically evident vitamin E deficiency due to a mutation of the α-TTP have been described (Cavalier et al., 1998). The prevalence of less drastic abnormalities in TTP, or the occurrence of heterozygotes for α-TTP gene defects, is not known. It is important to note that symptoms associated with TTP defects and malabsorption syndromes can be reversed by vitamin E supplementation if it is provided before irreversible neurological injury occurs (Kohlschütter et al., 1988; Muller et al., 1985; Schuelke et al., 1999; Sokol et al., 1985, 1988).

The primary human vitamin E deficiency symptom is a peripheral neuropathy characterized by the degeneration of the large-caliber axons in the sensory neurons (Sokol, 1988). Other vitamin E deficiency symptoms observed in humans include spinocerebellar ataxia, skeletal myopathy, and pigmented retinopathy (Sokol, 1993). Typical symptoms of vitamin E deficiency are given in Table 6-2.

A distinct pattern in the progression of neurologic symptoms resulting from vitamin E deficiency in humans has been described (Sokol, 1993). By the end of the first decade of life untreated patients with chronic cholestatic hepatobiliary disease have a combination of spinocerebellar ataxia, neuropathy, and ophthalmoplegia. However, the progression of neurological symptoms is slower in children with cystic fibrosis and abetalipoproteinemia. The symptomatology of vitamin E deficiency in AVED is similar to that found in these latter patients (Amiel et al., 1995; Sokol et al., 1988). These