74 THE EFFICACY OF TPGS TREATMENT ON THE PERIPHERAL NERVOUS SYSTEM FUNCTION, LIPID PEROXIDES AND POLYUNSATURATED FATTY ACIDS IN CHILDREN WITH CHRONIC CHOLESTASIS

Abstract

Prolonged Vitamin E deficiency in childhood induced by chronic cholestasis leads to a degenerative neurologic disorder. We studied the effect of long-term water-soluble α-tocopherol polyethylene glycol succinate (TPGS) therapy on serum α-tocopherol levels, plasma lipid peroxides (expressed as TBARS, nmol/ml), plasma phospholipid fatty acid profile and neurological function quantitated by EMG examination in 15 children with chronic cholestasis aged 9 month to 3;5 years (median 1,4 year). All children presented with low vitamin E serum concentrations [1.95(0.8-3.7) mg/l; median (1st-3rd quartile)]. The previous supplementation of α-tocopherol was replaced by a 20% solution of TPGS in a daily dose of 20 IU/kg. The biochemistry was done at the beginning of the study, after 1 month and after 1 year of TPGS treatment. EMG was measured correspondingly at the beginning, 3 months and 1 year later. The results of fatty acid levels, TBARS and EMG were related to own normal values. α-tocopherol levels were significantly increased after 1 months [6.9(4.4-8.4) mg/l; P=0.008] and rose further after a year [9.7(7.2-14.9)]. Similar results were obtained for the ratio vit.E/total lipids. TBARS were increased in cholestatic patients at baseline [2.9 (1.5-3.32) vs 1.2(1.1-1.3); P<0.001] and did not change significantly during 1 year TPGS therapy [2.34 (1.9-3.0)]. The contributions of fatty acids to total phospholipid fatty acids (%w/w) showed significant deficiency of polyunsaturated fatty acids (PUFA) at the beginning [27.7(22.4-31.5) vs 36.9(34.5-39.0); P=0.001], which did not change during the therapy [after 1 y 24.75(20.73-32.5); P>0.05]. Electrophysiological studies of nerves and muscles reveled at baseline slight signs of neuroaxonal neuropathy, especially sensory, located mainly in the lower limbs and muscular denervation pattern, both in the upper and lower limbs. Subsequent clinical and electrophysiological investigations displayed imperceptible recovery after 3 months but marked recovery after 12 months. Conclusions: Oral TPGS supplementation of cholestatic children can quickly normalise serum vitamin E levels and it has influence on the nervous system function but this does not improve increased lipid peroxidation and poor polyunsaturated fatty acid status. This study was carried out within a research project financed by the KBN, Warsaw (s4 405 00 405), Deutsche Forschungsgemeinschaft, Bonn (Ko.912/4-2) and Nestec Ltd., Vevey (S.85/93).