JuneK. Lloyd

VITAMIN E AND NEUROLOGICAL FUNCTION

Three lines of evidence indicate that vitamin E is important for normal neurological function in man. First, in abetalipoproteinaemia early therapy with vitamin E delays, and may prevent, the development of neurological complications, and in patients with established lesions treatment can arrest or reverse the neuropathy. Secondly, in other chronic disorders of fat absorption with severe vitamin E deficiency, neurological manifestations can be improved by vitamin E. Thirdly, the neuropathological changes observed in vitamin-E-deficient states in man (such as abetalipoproteinaemia, chronic liver disease, and cystic fibrosis) are similar to those reported in vitamin-E-deficient rats and monkeys.

INTESTINAL ENTEROKINASE DEFICIENCY

Abstract An infant presenting with diarrhœa, failure to thrive, and hypoproteinaemic œdema was shown to have deficiency of intestinal enterokinase which resulted in failure to activate pancreatic proteolytic enzymes.

Long-term follow-up of children with familial hypercholesterolaemia treated with cholestyramine.

35 children with the heterozygous form of familial hypercholesterolaemia (FH) who were followed for up to 8 years after starting on cholestyramine treatment showed a progressive decrease in compliance with therapy with time, so that only 55% remained on treatment after 6 years and only 48% after 8 years. Long-term compliance was significantly better in those starting treatment before age 10. Plasma-cholesterol was lowered in all children taking cholestyramine: for the group the mean reduction in plasma-cholesterol ranged from 26 to 44% during the years of the study, on a mean cholestyramine dose of around 0.4 g/kg/day. Cholestyramine thus effectively lowers plasma-cholesterol in FH, but for long-term use compliance is a problem in many children.

Diagnosing familial hypercholesterolaemia in childhood by measuring serum cholesterol.

The serum cholesterol concentrations of 134 children aged 1-16 years who had at least one first-degree relative with presumed familial hypercholesterolaemia showed a bimodal distribution, and, using the maximum likelihood technique, two overlapping curves could be fitted. The mean value of the affected children (heterozygotes) was 8-9 mmol/l and that of the unaffected 4-9 mmol/l. The two curves intersected at 6-77 mmol/l, and at this point 5% of the unaffected children had values over 6-77 mmol/l and 3-5% of the heterozygotes had values under 6-77 mmol/l. If this cholesterol concentration is used as a cut-off point 4-25% of cases would be misdiagnosed.

FAMILIAL α-LIPOPROTEIN DEFICIENCY (TANGIER DISEASE) WITH NEUROLOGICAL ABNORMALITIES

Abstract A patient with α-lipoprotein deficiency presented with widespread dissociated loss of pain and temperature sensation and progressive focal muscle wasting and weakness. Electrical and histological investigations revealed disordered function and structure of the peripheral nerves. The typical pharyngeal appearance was present, and cholesterol ester was demonstrated in the sternal marrow and rectal mucosa. The small amount of α-lipoprotein present contained an excessive proportion of triglyceride. An increased proportion of triglyceride was also present in β-lipoprotein. Studies of the serum-lipoproteins in relatives confirmed the familial nature of the defect.

The Role of Vitamin E in the Treatment of the Neurological Features of Abetalipoproteinaemia and Other Disorders of Fat Absorption

Studies in patients with abetalipoproteinaemia and other chronic and severe fat malabsorptive states, and neuropathological studies in the vitamin E-deficient human, monkey and rat indicate that vitamin E is important for normal neurological function. Appropriate vitamin E supplementation is, therefore, advisable for all patients with chronic fat malabsorption who have low serum vitamin E concentrations.

Treatment of familial hypercholesterolaemia in children.

Abstract Thirteen children with the heterozygous form of familial hypercholesterolaemia were treated by a diet low in ordinary fat (largely saturated) and supplemented with cornoil foods (rich in polyunsaturated fatty acids). A mean reduction in serum-cholesterol of 24% was achieved: the greater the amount of ordinary fat in the diet the smaller was the reduction in serum-cholesterol, but there was no correlation between the amount of corn oil and the reduction in serum-cholesterol. It seems that corn oil has no specific hypocholesterolaemic action in familial hypercholesterolaemia, but it is still important in treatment since it greatly improves the palatability of a diet low in ordinary fat. It also avoids the need for a high-carbohydrate intake which may lead to hypertriglyceridaemia. Clofibrate, given in addition to diet, decreased the serum-cholesterol further, and resulted in a mean total reduction of 33%. One child with the homozygous form has been treated for 2 years with diet, clofibrate, and cholestyramine. Serum-cholesterol fell by 32% and her xanthomas decreased both in size and number.

Use of medium-chain triglyceride diets in children with malabsorption.

Medium-chain triglyceride (MCT) contains fatty acids with 8 or 10 carbon atoms and differs from long-chain triglyceride (LCT, containing fatty acids with 12 or more carbon atoms) in its water miscibility, its faster hydrolysis by pancreatic lipase, its ability to enter the intestinal mucosal cell unhydrolyzed and to undergo hydrolysis within the cell, and in the subsequent transport of its fatty acids, which are carried in an albumin complex in the portal blood stream. These properties form the basis for the use of MCT in situations in which the absorption of ordinary dietary fat (predominantly LCT) is impaired, and MCT diets have been described in the treatment of various malabsorptive states: in obstructive jaundice (Burke and Danks, 1966; Linscheer et al., 1966) and cystic fibrosis (Kuo and Huang, 1965; Anderson, 1968), where there is defective intraluminar digestion; in tropical sprue (Cancio and MenendezCorrada, 1964) and after intestinal resection (Zurier et al., 1966; Winawer et al., 1966; Burke and Anderson, 1967), where the absorptive area is decreased; in a-3-lipoproteinaemia (Isselbacher et al., 1964; Lloyd, 1968), where chylomicrons cannot be formed; and in intestinal lymphangiectasia (Holt, 1964; Holt, Hashim, and Van Itallie, 1965; Yssing, Jensen, and Jarnum, 1967; Poley et al., 1967), where chyle flow is obstructed. Because of its calorific value of 83 cal./g. (Kaunitz et al., 1958), MCT is likely to be particularly useful in the treatment of malabsorption in childhood when growth failure is often a problem. Encouraging results in this respect have been reported in cystic fibrosis (Kuo and Huang, 1965; Anderson, 1968), in liver disease (Burke and Danks, 1966), and after intestinal resection (Burke and Anderson, 1967). We describe our experience with MCT in the

RED-CELL LIPIDS IN FAMILIAL ALPHALIPOPROTEIN DEFICIENCY (TANGIER DISEASE)

Abstract Studies of red-cell lipids in a patient with familial alphalipoprotein deficiency (Tangier disease) showed normal concentrations of total cholesterol and phospholipid but increased proportions of phosphatidyl choline and decreased proportions of sphingomyelin. The red-cell phospholipid abnormalities were similar to those present in the plasma-phospholipids and are the opposite of those found in the red-cells and plasma in a-betalipoproteinaemia.

THE NATURE AND OCCURRENCE OF PRE-BETA-LIPOPROTEIN IN DIABETIC CHILDREN AND PREGNANT WOMEN. AN ELECTROPHORETIC AND ULTRACENTRIFUGAL STUDY OF SERUM LIPOPROTEINS.

A marked increase in pre-beta-lipoprotein was found in eleven of twenty-one untreated diabetic children and six of twenty treated diabetic children. In both diabetic and nondiabetic pregnant women there was a steady increase in the amount of this lipoprotein after the sixteenth week of pregnancy whereas earlier in pregnancy a marked increase was found only in a small group of diabetic women (five of fifty-two). A detailed study of the nature of pre-beta-lipoprotein showed that the protein moiety is immunochemically the same as that of beta-lipoprotein, but that the lipid moiety contains more triglyceride and less cholesterol than that of beta-lipoprotein. Pre-beta-lipoprotein as defined by paper electrophoresis was found, on ultracentrifugal separation using the salt density gradient method, to have a flotation rate of Sf15–100. Paper electrophoresis provides a useful though rough means of recognizing excessive amounts of this lipoprotein. A marked pre-beta band suggests the presence of more than 125 mg. per 100 ml. of Sf15–100 lipoprotein-lipid. Studies of the lipid composition of Sf15–100, 10–15, 3–9 and high-density lipoproteins showed that, for each fraction, the lipid composition remains constant irrespective of the amount of total lipid within the fraction and irrespective of whether the individual is diabetic or nondiabetic, pregnant or nonpregnant.