Spinocerebellar Degeneration Associated with a Selective Defect of Vitamin E Absorption

Harding, A. E.; Matthews, Susan; Jones, Samantha K.; Ellis, Charles J.; Booth, I W; Muller, D. P. R.

doi:10.1056/nejm198507043130107

Cited by 165 publications

(58 citation statements)

References 18 publications

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“…However, in that study the only test of absorption was the measurement of plasma levels of tocopherol after a 2-g dose of a-tocopheryl acetate. Similar to the results of the oral vitamin E tolerance test carried out in the four patients studied here (8), the plasma tocopherol levels in the patient described by Harding et al (5) were found to increase to normal levels after 4 hours and remained elevated for 24 h. It is our contention that the absorption and secretion of tocopherol in chylomicrons is not impaired in these patients and that the catabolism ofchylomicrons following a large oral dose of vitamin E will provide the other plasma lipoproteins with tocopherol. However, if the dose of vitamin E is small, similar to dietary levels or the amounts fed in the present study, the amounts of tocopherol distributed to the lipoproteins during chylomicron catabolism is insufficient to maintain the plasma tocopherol at normal levels.…”

Section: Resultssupporting

confidence: 86%

“…Recently, nine patients worldwide have been described who exhibit similar neurologic abnormalities and vitamin E deficiency, but have no evidence of fat malabsorption (2)(3)(4)(5)(6)(7)(8). These patients all have normal lipid absorption, gastrointestinal, pancreatic, and intestinal function, and lipoproteins, but when consuming a normal diet, they have exquisitely low plasma vitamin E levels and develop neurologic abnormalities characteristic of vitamin E deficiency.…”

Section: Introductionmentioning

confidence: 99%

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Impaired ability of patients with familial isolated vitamin E deficiency to incorporate alpha-tocopherol into lipoproteins secreted by the liver.

Traber¹,

Sokol²,

Burton³

et al. 1990

J. Clin. Invest.

228

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Plasma and lipoprotein a-tocopherol concentrations of four patients with familial isolated vitamin E deficiency and six control subjects were observed for 4 d after an oral dose (-15 mg) of RRR-a-tocopheryl acetate labeled with six deuterium atoms (d6-tocopherol). Chylomicron d6-tocopherol concentrations were similar in the two groups. d6-Tocopherol concentrations of plasma, very low (VLDL), low (LDL), and high (HDL) density lipoproteins were similar in the two groups only during the first 12 h; then these were significantly lower, and the rate of disappearance faster, in the patients. The times (t.u) of the maximum chylomicron d6-tocopherol concentrations were similar for the two groups, but t1.,,, values in the controls increased in the order: chylomicrons < VLDL . LDL -HDL, while the corresponding values in the patients were similar to the chylomicron t,. Thus, plasma d4-tocopherol in controls increased during chylomicron and VLDL catabolism, whereas in patients it increased only during chylomicron catabolism, thereby resulting in a premature and faster decline in the plasma tocopherol concentration due to a lack of d6-tocopherol secretion from the liver. We suggest that these patients are lacking or have a defective liver "tocopherol binding protein" that incorporates a-tocopherol into nascent VLDL. (J. Clin. Invest. 1990. 85:397-407.) deuterated a-tocopherol * tocopherol binding protein Introduction Humans do not readily become vitamin E deficient. It has been generally accepted that the quantities of vitamin E in the diet are adequate and that the vitamin E stores in the body are sufficient to prevent any symptoms of vitamin E deficiency from occurring even in the face of a prolonged absence of dietary vitamin E. However, vitamin E deficiency does occur in humans as a consequence ofa variety oflipid malabsorption syndromes, most notably as a result of cholestatic liver disease in children, and in the genetic disorders, abetalipoproteinemia and homozygous hypobetalipoproteinemia (as reviewed in 1).

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Section: Resultssupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Impaired ability of patients with familial isolated vitamin E deficiency to incorporate alpha-tocopherol into lipoproteins secreted by the liver.

Traber¹,

Sokol²,

Burton³

et al. 1990

J. Clin. Invest.

228

View full text Add to dashboard Cite

show abstract

“…Acting as a chain reaction terminator by donating a hydrogen atom, a-tocopherol has the ability to inhibit generation of singlet oxygen, free radicals, lipid radicals and lipid hydroperoxides [5] and thereby protect polyunsaturated fatty acids as components of phospholipids in cell membranes. Clinical symptoms of vitamin E deficiency, mainly affecting the nervous sys tem, have been described in patients with different lipid malabsorption syndromes [6][7][8], Another factor in the antioxidant defence system is glutathione peroxidase. This en zyme uses selenium as cofactor and gluta thione as a proton donor when inactivating lipid peroxidation products and oxygen in termediates in cytosol [9).…”

Section: Introductionmentioning

confidence: 99%

“…Increased lipid peroxidation and en hanced activity of free radicals have been reported in alcoholics [10,11] and may be important factors in development of liver diseases [12], neurological dysfunction [7,13], cardiovascular diseases [14] and cancer [15,16].…”

Section: Introductionmentioning

confidence: 99%

Diminished Serum Concentration of Vitamin E in Alcoholics

Bjørneboe¹,

Johnsen²,

Bjørneboe³

et al. 1988

Ann Nutr Metab

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The effect of heavy alcohol consumption on serum concentrations of vitamin E (α-tocopherol) and selenium was studied in 13 alcoholics and 19 control subjects. Ethanol intake during the year previous to the study was in the range from 22 to 354 g/day and from 0 to 16 g/day among the alcoholics and controls, respectively. Of the 13 alcoholics, 6 had a serum concentration of α-tocopherol below the lower limit of reference (14 µmol/l) and mean serum concentration of α-tocopherol was reduced by 37% as compared to controls (p < 0.002). Estimated dietary intake of α-tocopherol during the year previous to the study was approximately 40% lower for the alcoholics (p < 0.05). During hard-drinking periods the alcoholics had a markedly reduced intake of α-tocopherol as compared to moderate-drinking and abstinent periods. Mean serum concentration of selenium was significantly reduced in the alcoholics (1.2 ± 0.3 µmol/l) as compared to the controls (1.6 ± 0.2 µmol/l) (p < 0.002). The reduced serum levels of α-tocopherol and selenium may influence the maintenance of normal cell structure and function, and contribute to development of diseases frequently observed in alcoholics.

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“…Vitamin E deficiency affects both the central and peripheral nervous systems (11). The associated peripheral neuropathy is most often axonal (11), although demyelinating neuropathy also occurs (12).…”

Section: Vesterhus and Associatesmentioning

confidence: 99%

Neurological Features and Enzyme Therapy in Patients With Endocrine and Exocrine Pancreas Dysfunction Due to CEL Mutations

et al. 2008

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OBJECTIVE -To further define clinical features associated with the syndrome of diabetes and pancreatic exocrine dysfunction due to mutations in the carboxyl-ester lipase (CEL) gene and to assess the effects of pancreatic enzyme substitution therapy.RESEARCH DESIGN AND METHODS -Nine patients with CEL gene mutation, exocrine deficiency, and diabetes were treated and followed for 30 months.RESULTS -Treatment improved symptoms in seven of nine patients. Exocrine and endocrine function assessed by fecal elastase and A1C were not affected, although fecal lipid excretion was reduced. Vitamin E was low in all patients but increased with treatment (P Ͻ 0.001 at 30 months) and improved in five subjects. A predominantly demyelinating neuropathy was seen in a majority of patients, and carpal tunnel syndrome was common.CONCLUSIONS -Pancreatic enzyme substitution alleviated symptoms and malabsorption and normalized vitamin E levels. Glycemic control was not significantly affected. The CEL syndrome seems associated with a demyelinating neuropathology.

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Spinocerebellar Degeneration Associated with a Selective Defect of Vitamin E Absorption

Cited by 165 publications

References 18 publications

Impaired ability of patients with familial isolated vitamin E deficiency to incorporate alpha-tocopherol into lipoproteins secreted by the liver.

Impaired ability of patients with familial isolated vitamin E deficiency to incorporate alpha-tocopherol into lipoproteins secreted by the liver.

Diminished Serum Concentration of Vitamin E in Alcoholics

Neurological Features and Enzyme Therapy in Patients With Endocrine and Exocrine Pancreas Dysfunction Due to CEL Mutations

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