Cholesterol Deficiency Research Articles

A cholesterol deficiency syndrome in humans.

A cholesterol deficiency syndrome in humans.

Induction of maturation of cumulus-oocyte complex by gonadotropin-releasing hormone analog is associated with lower progesterone secretion.

Induction of ovulation by CG in women subjected to in vitro fertilization and embryo transfer results in maturation of the cumulus-oocyte complex (COC) in terms of oocyte meiotic maturation, cumulus mucification, and an increase in progesterone (P4) secretion. Recently an alternative approach, in which the ovulatory processes are induced by the administration of GnRH analog (GnRHa), has resulted in COCs yielding viable embryos. In the present study the effect of GnRHa administration on oocyte meiotic maturation and cumulus cell steroidogenesis was evaluated in 27 women undergoing ovarian stimulation with gonadotropin for the purpose of in vitro fertilization and embryo transfer. In GnRHa- or CG-treated women, 79.5 +/- 4.2% and 72.0 +/- 8.4% of the oocytes, respectively, manifested the first polar body. The percentages of atretic oocytes and of oocytes failing to resume meiosis were 5.8 +/- 2.1% and 6.0 +/- 2.4%, respectively, in GnRHa-treated women, and were 9.3 +/- 4.7% and 7.9 +/- 4.1%, respectively, in CG-treated women. P4 was secreted in high quantity in human cumulus cells (CCs) during a 7-day culture period. However, in CCs collected from GnRHa-treated women, P4 secretion was more than 50% less than in CCs of CG-treated women (P < 0.005). Addition of 20 alpha-hydroxycholesterol significantly increased P4 secretion in CCs collected from GnRHa-treated women, similar to P4 secretion in CCs collected from CG-treated women. This study evaluated for the first time the effectiveness of GnRHa administration on COC maturation. It seems that although oocyte meiotic maturation in GnRHa-treated women proceeds as in CG-stimulated women, CC steroidogenic activity is marked by cholesterol deficiency or availability.

Homozygous Tangier disease and cardiovascular disease

Decreased levels of plasma high density lipoprotein (HDL) cholesterol have been associated with premature cardiovascular disease (CVD). Tangier disease is an autosomal co-dominant disorder in which homozygotes have a marked deficiency of HDL cholesterol and apolipoprotein (apo) A-I levels (both < 10 mg/dl), decreased low density lipoprotein (LDL) cholesterol levels (about 40% of normal), and mild hypertriglyceridemia. Homozygotes develop cholesterol ester deposition in tonsils (orange tonsils), liver, spleen, gastrointestinal tract, lymph nodes, bone marrow, and Schwann cells. Our purpose was to assess the prevalence of CVD in Tangier disease. We reviewed published clinical information on 51 cases of homozygous Tangier disease, report 3 new cases and provide autopsy information on 3 cases. Mean (±S.D.) lipid values of all cases were as follows: total cholesterol 68 ± 30 mg/dl (32% of normal), triglycerides 201 ± 118 mg/dl (162% of normal), HDL cholesterol 3 ± 3 mg/dl (6% of normal) and LDL cholesterol 50 ± 38 mg/dl (37% of normal). The most common clinical finding in these subjects ( n = 54) was peripheral neuropathy which was observed in 54% of cases versus < 1% of control subjects ( n = 3130). CVD was observed in 20% of Tangier patients versus 5% of controls ( P < 0.05), and in those that were between 35 and 65 years of age, 44% (11 of 25) had evidence of CVD (either angina, myocardial infarction or stroke) versus 6.5% in 1533 male controls and 3.2% in 1597 female controls in this age group ( P < 0.01). In 9 patients who died, 2 died prior to age 20 of probable infectious diseases, 3 of documented coronary heart disease at ages 48, 64, and 72, 2 of stroke at ages 56 and 69, one of valvular heart disease, and 1 of cancer. In three autopsy cases, significant diffuse atherosclerosis was observed in one at age 64, moderate atherosclerosis and cerebral infarction in another at age 56, but no atherosclerosis was noted in the third case who died of lymphoma at age 62. In one patient with established coronary heart disease, none of the lipid lowering agents used (niacin, gemfibrozil, estrogen or lovastatin) raised HDL cholesterol levels above 5 mg/dl. However, these agents did have significant effects on lowering triglyceride and LDL cholesterol levels. Our data indicate that there may be heterogeneity in these patients with regard to CVD risk, that peripheral neuropathy is a major problem in many patients, and that CVD is a significant clinical problem in middle aged and elderly Tangier homozygotes. These patients may be somewhat protected from strikingly premature CVD because of their low LDL cholesterol levels, but their CVD prevalence is at least six-fold higher than normal between the ages of 35 and 65 years. Both the apo A-I and apo MI genes have been noted to be normal in selected cases. The precise defect in Tangier disease remains unknown and clear guidelines for therapy have not been developed. However, it is prudent to treat CVD risk factors in these patients when present, especially hypertension, cigarette smoking, and diabetes.

HMG‐CoA reductase mRNA in the post‐implantation rat embryo studied by in situ hybridization

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) is the rate limiting step in the mevalonate pathway that produces isoprenoids and cholesterol. Inhibitors of HMG-CoA reductase are teratogenic in vivo and induce neural tube defects in rat embryo culture, effects which appear unrelated to cholesterol deficiency. This study is the first to localize HMG-CoA reductase mRNA by in situ hybridization (ISH). Expression of reductase mRNA was examined in post-implantation rat embryos, and for control purposes in rat liver and UT-1 cells, using a digoxigenin-11 (dig-11) labelled cRNA probe. Eighteen-day fetal liver showed heavy but patchy hybridization, and adult rat liver showed strong hybridization only on some periportal hepatocytes, which was absent in livers of fasted animals. UT-1 cells stimulated to overexpress HMG-CoA reductase mRNA were strongly positive with the same probe. Control hybridizations with sense strand RNA probe, or with cRNA probe on pre-RNased tissue were negative. Strong hybridization signal for HMG-CoA reductase mRNA was observed in all tissues of the post-implantation rat embryo, from egg cylinder to 30 somite stages (7 to 12 days). Heavy signal was noted in primitive ectoderm and neural tube. The wide embryonic and extraembryonic distribution and abundance of HMG-CoA reductase mRNA may reflect developmental requirements for products of the mevalonate pathway, e.g., isoprenoids for post-translational farnesylation of p21ras.

Reduced sensitivity of cultured skin fibroblasts from familial hypercholesterolemic patients to glucocorticoids

Cultured human skin fibroblasts, obtained from patients with homozygous familial hypercholesterolemia (FH), exhibited cholesterol synthesis that was 2.5–3-fold more intensive than in cells from healthy donors (normal cells). The study of the glucocorticoid [ 3H]-dexamethasone specific binding (glucocorticoid receptors, GcR) to the cells showed reduced number of binding sites (8×10 3 vs 120×10 3 binding sites/cell) and reduced Kd value (5.6±0.7 vs 10.1±2.1 nM) in FH-fibroblasts when compared with normal fibroblasts. The inhibition by 1×10 −8 and 1 × 10 −6 M dexamethasone of cholesterol synthesis was less marked in FH-cells (29.1±2.8 and 35.9±1.2%) as compared with normal cells (53.3±1.0% and 60.4±9.6, respectively). This findings indicate that the sensitivity of FH-fibroblasts to glucocorticoids is reduced. They also suggest that reduced number of GcR found in FH-fibroblasts reflects the cellular adaptation to cholesterol deficiency resulted from the absence of LDL-receptors.

A ‘Fish-eye disease’ familial condition with massive corneal opacities and hypoalphalipoproteinaemia: clinical, biochemical and genetic features

A Caucasian family of mediterranean origin comprising a patient whose parents were first cousins, his wife and their three children, and his two sisters have been studied. The patient and his two daughters were afflicted with the same corneal opacities and hypoalphalipoproteinaemia. The disease was shown to be transmitted as a non-sex-linked recessive trait. The corneal opacities develop at the end of the second decade of life and consist of numerous minute greyish dots in the entire corneal stroma that give the cornea a misty appearance. Vision slowly deteriorated from 40 years of age. At about 50 years of age, except in one of the two daughters who showed Marfanoid syndrome, the three patients had good general health and no symptoms of atherosclerosis. Biochemical investigations showed hypoalphalipoproteinaemia (with a faint fast-moving HDL band on polyacrylamide gel gradient electrophoresis and small arcs of HDL2 and HDL3 of low mobility determined by agarose gel immunoelectrophoresis), low total cholesterol (3.5-4.9 mmol l-1), slightly decreased cholesteryl ester/total cholesterol ratio (0.52-0.63), extremely low HDL cholesterol (0.20-0.21 mmol l-1), mild hypertriglyceridaemia (1.94-3.80 mmol l-1), and striking deficiency in apo A-I and apo A-II (0.45-0.72, 0.08-0.16 g l-1, respectively). The esterification of HDL cholesterol was low while that of LDL and VLDL was nearly normal. Other laboratory values were normal. The HDL subspecies and major apolipoprotein isoforms have been studied to differentiate FED from Tangier disease, LCAT deficiency, as Apo A-I, A-II, C-II, C-III deficiencies and variants.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhancement of Thyroxine Entry into Low Density Lipoprotein (LDL) Receptor-Competent Fibroblasts by LDL: An Additional Mode of Entry of Thyroxine into Cells

Having demonstrated that plasma low density lipoproteins (LDL) bind T4 through a specific interaction with their sole apolipoprotein, apoB-100, we tested the hypothesis that cells could internalize the LDL-T4 complex via cell surface LDL receptors. These receptors are down-regulated by cholesterol loading and up-regulated by cholesterol deficiency. We, therefore, studied the uptake of [125I]T4 or [125I]T3 by human skin fibroblasts grown in 10% lipoprotein-deficient serum in the absence or presence of LDL. At concentrations of LDL (12.5 and 22 micrograms protein/ml) that gave significant binding of T4 but did not exceed LDL receptor capacity, both the initial rate of saturable T4 uptake and the uptake at equilibrium increased by 27-63%. No significant increase occurred at a LDL concentration of 1.6 micrograms protein/ml (less than 3% occupancy), whereas there was a 20 to 31% reduction at 125 micrograms/ml (approximately 5 times the saturation dose for the LDL receptor). These changes were confirmed with several different LDL preparations and were mimicked by isolated apoB-100 and apoE, the sole ligands for the LDL receptors (apoB/E receptors). T4 uptake did not increase in normal fibroblasts with down-regulated LDL receptors or in LDL receptor-deficient fibroblasts from a patient with familial hypercholesterolemia. In the latter cell line the uptake of T4 (and T3) in the absence of LDL was indistinguishable from that of normal fibroblasts. T3 uptake in normal fibroblasts was not enhanced by LDL. The specificity of the LDL effect was shown by the finding that T4-binding globulin, prealbumin, or serum albumin, at concentrations giving 10-90% T4 bound, failed to increase T4 uptake. Instead, each of these major thyroid hormone-binding plasma proteins caused a dose-dependent decrease in T4 entry. It is concluded that at least two modes of entry into fibroblasts are available for T4. The first is the cell surface thyroid hormone-binding sites, which recognize the free hormone and are present in both normal and LDL receptor-negative fibroblasts. The second, and additional, mode of entry is via the LDL receptors, which recognize the T4-LDL complex, are absent in LDL receptor-negative fibroblasts, are reduced in down-regulated fibroblasts, and are unavailable for T3, owing to the low affinity of T3 for LDL.

The role of substrate supply in the regulation of cholesterol biosynthesis in rat hepatocytes.

1. Compactin, (-)-hydroxycitrate and dexamethasone gave rise to a decrease in the rate of cholesterol production in hepatocytes from fed rats by interfering with the flow of substrate into the sterol biosynthetic pathway. The cells responded to the deficit of biosynthetic sterol by increasing the activity of hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase). 2. Compactin and (-)-hydroxycitrate gave similar results in hepatocytes from rats starved for 24 h but in this case dexamethasone had no significant effect. 3. Exogenous oleate interferes with the production of carbohydrate-derived acetyl-CoA and also gives rise initially to opposing effects on the rate of sterol synthesis and HMG-CoA reductase activity. Over a longer period, however, oleate itself was capable of replacing carbohydrate as the major source of carbon for sterol synthesis. 4. The increase in HMG-CoA reductase activity observed when liver cells were incubated in the presence of compactin, (-)-hydroxycitrate or oleate could be partially reversed by the simultaneous presence of glucagon. 5. Under some physiological conditions, a deficiency of biosynthetic cholesterol or of a related precursor may lead to an increase in the activity of HMG-CoA reductase.

The topography of filipin-cholesterol complexes in the plasma membrane of cultured hepatocytes and their relation to cell junction formation

The present study, employing freeze-fracture and filipin as a cytochemical marker for cholesterol or cholesterol-like components in cell membranes, shows that there is an apparent heterogeneity in the distribution of filipin-cholesterol complexes in the plasma membranes of cultured hepatocytes, thus indicating differences in their cholesterol content. A high number of filipin-cholesterol complexes are uniformly and randomly distributed over the entire plasma membrane of isolated hepatocytes. A similar pattern was observed in the upper and lower plasma membranes of cultured hepatocytes, whereas the plasma membrane areas between adjoining hepatocytes contained far fewer filipin-cholesterol complexes. Tight junction and gap junction formation zones show a nearly complete absence of filipin-cholesterol complexes. It is suggested that changes in membrane fluidity due to the low cholesterol content may play a role in the recognition and adhesion of cultured hepatocytes. The localized deficiency of cholesterol in specialized domains of the plasma membranes recognized as early junction formation zones may facilitate the essential adhesion between cell surfaces and may alter lipid-protein interactions which further affect assembly of tight or gap junctions.

Receptor-mediated uptake of low density lipoprotein reconstituted with 25-hydroxycholesteryl oleate suppresses 3-hydroxy-3-methylglutaryl-coenzyme A reductase and inhibits growth of human fibroblasts

The free and esterified cholesterols of plasma low density lipoprotein (LDL) were extracted with heptane and replaced with 25-hydroxycholesteryl oleate. The resulting particle, designated r-[25-HC oleate]LDL, bound to LDL receptors on human fibroblasts, was taken up by adsorptive endocytosis and was hydrolyzed in lysosomes in a manner similar to that of native LDL. The r-[25-HC oleate]LDL suppressed 3-hydroxy-3-methylglutaryl-coenzyme A reductase [mevalonate:NADP(+) oxidoreductase (CoA-acylating), EC 1.1.1.34], the enzyme catalyzing the rate-limiting step in cholesterol biosynthesis. This suppression did not occur when lysosomal hydrolysis of r-[25-HC oleate]LDL was inhibited by chloroquine. When fibroblasts were incubated with r-[25-HC oleate]LDL in the absence of a source of cholesterol, the cells developed an abnormal morphology, their growth was inhibited, and the cells died. The toxic effects of r-[25-HC oleate]LDL were prevented when the growth medium was supplemented with cholesterol in ethanol or with mevalonate, the product of the reductase reaction. These data suggest that the toxicity of r-[25-HC oleate]LDL was due to its suppression of reductase, which in turn caused cellular cholesterol deficiency. The r-[25-HC oleate]LDL did not suppress reductase activity nor did it alter the growth or morphology of mutant fibroblasts lacking LDL receptors, which were obtained from a patient with homozygous familial hypercholesterolemia. These experiments demonstrate the feasibility of using reconstituted LDL to selectively deliver hydrophobic compounds other than typical cholesteryl esters to cells possessing LDL receptors.

Membrane lipid changes associated with malignant transformation and normal maturation of human lymphocytes

Human lymphocytes from normal blood, normal thymus, chronic lymphocytic leukaemia blood and lymphoblasts from continuous cell lines were studied as representative of normal, immature and transformed lymphocytes in an attempt to determine whether a relationship exists between the lipid composition of the plasma membrane and the maturity or malignant transformation of the lymphocyte. Normal mature lymphocytes from peripheral blood contain more phospholipid and cholesterol per cell than immature thymocytes or chronic lymphocytic leukaemia cells suggesting that the normal maturation of lymphocytes is associated with an increase in the content of these lipids. Analysis of plasma membrane preparations from the four populations of lymphocytes showed that, when assayed on a per cell basis, the cholesterol : phospholipid molar ratio of malignant and transformed lymphocyte membranes is substantially lower than that from normal lymphocytes. In the case of chronic lymphocytic leukaemia cells this deficiency of membrane cholesterol may be due to a decreased ability of the cells to synthesise sterols. The fatty acid composition of the major membrane phospholipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) also differed between the four lymphocyte populations studied. These observations of membrane phospholipid and cholesterol composition are consistent with previous assessments of the fluidity of the lipid core of normal and leukaemic lymphocyte membranes, but do not correlate with measurements of membrane dynamics using fluorescent antibody or lectins. This discrepancy is discussed.

Effect of cholesterol deficiency on the composition of phospholipids and fatty acids of the housefly, Musca domestica

The housefly larvae were grown in the aseptic diet containing 0.56 μmole cholesterol/g wet weight of diet (control) and 0.05 μmole cholesterol/g wet weight of diet (deficient). The effects of cholesterol deficiency upon the phospholipid composition and fatty acids of the total phospholipid and triglyceride fractions from the lipid extract of the various larval tissues, whole larva, and in both sexes of adults 4 days after eclosion were examined. The total sterol and phospholipid contents (expressed relative to the wet weight of the insect) of the control and deficient insects at the larval and adult stages were analysed and molar ratios compared. The results suggest that cholesterol deficiency reduced the free sterol content of the larvae and adult insects to approximately 25% of the content of the control insects. However, cholesterol deficiency did not effect the phospholipid content during larval and adult stages when compared to that of control insects. Though the larvae reared on the cholesterol deficient diets did not show a profound alteration in the phospholipid composition, a marked increase in the ratio of phosphatidylcholine to phosphatidylethanolamine of the larval fat body and composite gut fraction were noticed. The cholesterol deficiency induced significant changes in the fatty acid composition of the phospholipid fraction of the insect. The ratio of unsaturated fatty acids to saturated fatty acids of the phospholipid fractions decreased significantly due to cholesterol deficiency in the whole larvae and in both sexes of adult flies. The data indicates that cholesterol deficient insects compensated for the lack of cholesterol by increasing saturated fatty acids preferentially in the phospholipid fraction of the lipids for the maintenance of proper membrane fluidity.

Effect of dietary cholesterol deficiency upon its distribution in the larvae of the housefly, Musca domestica

The free sterol, total phospholipids and protein content of the various tissues and haemolymph lipoproteins obtained from the larvae of Musca domestica, reared on the diets containing 0.56 μmole cholesterol/g wet weight of diet (normal) and 0.05 μmole cholesterol/g wet weight of diet (deficient) have been determined. The cholesterol in the diet was found to be taken up by the larvae and distributed between all the tissues examined. About 60% of the free sterol in the larvae was recovered from the composite gut fraction and muscle. Cholesterol deficiency reduced both the growth of larvae and the free sterol content of the various tissues and haemolymph when compared to that of normal larvae. Cholesterol deficiency resulted in a slightly higher proportion of sterol and protein of the larval haemolymph being associated with the lipoproteins having slower electrophoretic mobility. Most of the different tissues from the cholesterol deficient larvae contained a much smaller proportion of their normal free sterol content than of their phospholipid or protein; the brain tissue however contained a higher percentage of free sterol and the haemolymph a much lower percentage than would be expected from the lowering of phospholipid and protein content as a result of the deficiency. When the sterol content was expressed relative to the protein, the ratio was higher in the brain tissue of both the normal and deficient larvae than the ratio present in the remaining tissues, apart from the composite gut fraction of the normal larvae. The results suggest that a disproportionate amount of available cholesterol was being concentrated into the nervous system of the cholesterol deficient insect. A rather higher proportion of the total sterol fraction recovered from the various tissues and haemolymph lipoproteins of cholesterol deficient larvae behaved as ‘polar metabolites’ of cholesterol when compared with that of normal larvae.

Cholesterol Requirements of Juvenile American Lobster (Homarus americanus)

In preliminary feeding trials with juvenile American lobsters (Homarus americanus) there were some differences in growth and survival that appeared to be related to deletion or addition of cod liver oil, mineral salts, vitamins, and glucosamine. However, the results were questionable due to deficiency of dietary cholesterol. Only when 1% cholesterol was added to the control diet was growth and survival achieved similar to that of lobsters fed brine shrimp. The optimum or required level of cholesterol was found to be approximately 0.5% of the dry weight of the diet.

Cholesterol as a bioregulator in the development and inhibition of leukemia.

Leukemia in mice and humans is accompanied by a marked deficiency of unesterified cholesterol in the surface membrane of leukemic cells as compared to normal leukocytes. This deficiency induces a significant reduction in their membrane microviscosity. Since cholesterol in the cell surface membrane is exchangeable with cholesterol in the serum lipoproteins, concomitant to the cellular deficiency of cholesterol, the average level of cholesterol in the blood serum of leukemic patients is substantially below the average normal level. Based on these observations and the effect of membrane microviscosity on biological functions, a working hypothesis that describes the role of cholesterol in the development and inhibition of leukemia is suggested. This hypothesis can also account for the effect of cholesterol and membrane microviscosity on various other cellular activities of leukocytes.

Cholesterol—Bile Acid Interactions in Gallstone Pathogenesis

A technique for direct sampling of gallbladder and hepatic bile in humans provides strong support for the view that gallstones develop when bile becomes lithogenic—i.e., when the bile acid-phospholipid to cholesterol ratio exceeds 10: 1. Lithogenic bile may develop in normal persons through diurnal variation in bile lipid composition or result from excess secretion of biliary cholesterol and/or bile acid deficiency.

Nutritional Status and Intestinal Function Among Rural Populations of the West Indies: II. Barrio Nuevo, Puerto Rico

Dietary intake, nutritional status, and intestinal structure and function were evaluated in 96 representative adult residents of a rural barrio in Puerto Rico. Deficiencies noted included mild anemia in 4, reduced serum concentrations of iron in 10, folate in 6, vitamin B12 in 1, albumin in 4, carotene in 6, and cholesterol in 7. Thirty-two persons had a single abnormal determination, and 11 had multiple abnormal determinations of intestinal function. These included xylose in 24, folic acid in 1, fat in 4, nitrogen in 1, and vitamin B12 in 28. Intestinal morphology was normal in 17 and showed mild changes in 48, moderate changes in 24, and severe abnormalities in 4. The incidence of certain intestinal abnormalities present during the winter months was double that noted during the summer. In 2 cases, malabsorption was clearly responsible for the development of nutritional deficiencies, but vitamin B12 deficiency was present in only 1 of the 28 subjects with malabsorption of this vitamin and xylose absorption was reduced in only 7 of the 21 persons who had a deficiency of either folate, albumin, carotene, or cholesterol. These observations indicate that the mildly compromised intestinal function found present in nearly one-half of the subjects evaluated does not, in most instances, result in the development of deficiency states in the presence of an adequate dietary intake.

The Role of Bile Acids in the Overall Regulation of Steroid Metabolism

Bile acids, themselves end products of cholesterol catabolism, act to regulate virtually every step in cholesterol metabolism, including dietary absorption, endogenous synthesis, excretion, and bile acid formation. Although many aspects of the interaction between bile acids and cholesterol are poorly understood, in regard to bile acid synthesis the effect of bile acids is homeostatic. On the one hand, bile acid formation increases following bile acid deprivation in order to provide adequate bile acids to maintain fat absorption, whereas bile acid excess in the diet or circulation is compensated by diminished bile acid synthesis. Furthermore, the net effect of bile acid on cholesterol metabolism is to maintain a balance in which synthesis and absorption tend to equal excretion and degradation under diverse physiological conditions and, thus, to minimize either cholesterol accrual or cholesterol deficiency.

The role of bile acids in the overall regulation of steroid metabolism

Bile acids, themselves end products of cholesterol catabolism, act to regulate virtually every step in cholesterol metabolism, including dietary absorption, endogenous synthesis, excretion, and bile acid formation. Although many aspects of the interaction between bile acids and cholesterol are poorly understood, in regard to bile acid synthesis the effect of bile acids is homeostatic. On the one hand, bile acid formation increases following bile acid deprivation in order to provide adequate bile acids to maintain fat absorption, whereas bile acid excess in the diet or circulation is compensated by diminished bile acid synthesis. Furthermore, the net effect of bile acid on cholesterol metabolism is to maintain a balance in which synthesis and absorption tend to equal excretion and degradation under diverse physiological conditions and, thus, to minimize either cholesterol accrual or cholesterol deficiency.

Familial hypo-β-lipoproteinaemia

A family with partial deficiency of serum β-lipoprotein and serum cholesterol is reported, in which 7 of the 8 members examined presented with a similar biochemical abnormality. The pedigree indicated an autosomal dominant inheritance for this abnormality. None of the family members presented acanthocytosis. The profile of the concentrations of serum lipids in this family was somewhat different from those of the reported families with hypo-β-lipoproteinaemia. Only one patient in this family presented neurological manifestations consisting of polyneuritis and papilloedema, which were dissimilar to those of the patients seen in the reported families. The clinical manifestations of this patient resemble the Guillain-Barré syndrome except for the very chronic evolution of the symptoms. The lack of neurological symptoms in other members of this family suggested that the neurological manifestations of the propositus could be a fortuitous association and that only the unusual chronic evolution of the symptoms was related to the hypo-β-lipoproteinaemia. However, it cannot be excluded also that the neurological manifestations were a direct consequence of the familial metabolic error.