Dysbetalipoproteinemia: an extreme disorder of remnant metabolism.

PURPOSE OF REVIEW: Lipoprotein metabolism and the role of apolipoprotein E in the pathogenesis of dysbetalipoproteinemia. RECENT FINDINGS: Remnant lipoproteins, modulated by lifestyle and genetic factors, are atherogenic. Dysbetalipoproteinemia could be viewed as a monogenic disorder of remnant metabolism. SUMMARY: Elevated plasma triglyceride and cholesterol concentrations (mixed hyperlipidemias) are commonly encountered and dysbetaliproteinemia should be considered in this setting. Dysbetalipoproteinemia (remnant clearance disease, Fredrickson type III hyperlipidemia) is an uncommon dyslipoproteinemia related to mutations in apolipoprotein E that disrupt the clearance of remnants of triglyceride-rich lipoproteins; it may be overlooked because xanthomata of the skin and/or tendons occur in a minority of patients. The diagnosis ideally requires the demonstration of remnant lipoprotein accumulation and a genetic cause. Genotyping for apolipoprotein E2 may not prove the diagnosis as it may be associated with low plasma lipid values. The recent association of remnant lipoproteins with atherosclerosis along with many factors that modulate remnant lipoprotein metabolism underscores the importance of recognising dysbetalipoproteinemia as an extreme state of remnant lipoprotein accumulation. Although there may be some differences between remnants in the general population and dysbetalipoproteinemia, it is clear that remnants promote atherosclerosis. Current treatment strategies are adequate but new strategies could also be of benefit in dysbetalipoproteinemia.

A dynamic model of calcific nodule destabilization in response to monocyte- and oxidized lipid-induced matrix metalloproteinases.

Vulnerable plaque remains clinically undetectable, and there is no accepted in vitro model. We characterize the calcific nodules produced by calcifying vascular cells (CVC) in ApoE-null mice, demonstrating increased destabilization of cultured nodules in the presence of oxidized low-density lipoprotein (oxLDL) and monocytes under pulsatile shear stress. CVC implanted in the subcutaneous space of hyperlipidemic mice produced nodules revealing features of calcific atherosclerotic plaque including a fibrous cap, cholesterol clefts, thin shoulder, lipids, and calcium mineral deposits. CVC nodules seeded in the pulsatile flow channel (τ(avg) = 23 dyn/cm(2), ∂τ/∂t = 71 dyn·cm(-2)·s(-1)) underwent deformation and destabilization. Computational fluid dynamics revealed distinct shear force profiles on the nodules. Presence of oxLDL or monocytic THP-1 cells significantly increased the numbers of nodules destabilized from the substrate. Both oxLDL and THP-1 increased matrix metalloproteinase (MMP) activity in CVC. The MMP inhibitor GM6001 significantly reversed oxLDL- and THP-1-induced nodule destabilization, whereas overexpression of MMP-9 increased destabilization. These findings demonstrate that CVC-derived nodules resembled calcific atherosclerotic plaque and were destabilized in the presence of active lipids and monocytes via induction of MMPs.

Xanthomata and diabetes in an adolescent with familial dysbetalipoproteinemia 9 yr after valproate-induced pancreatitis.

A 14-yr-old girl presented with eruptive xanthomata and hypertriglyceridemia. This rare presentation led to diagnoses of diabetes and familial dysbetalipoproteinemia. Type 1 diabetes is a common childhood illness often presenting in adolescence. However, this patient's past medical history revealed valproate-induced severe acute pancreatitis with necrosis at the age of 5 yr. Diabetes, in this case, developed 9 yr later as a result of inadequate pancreatic tissue to support increasing insulin requirements during growth and adolescence. Diabetes was discovered only after the appearance of cutaneous eruptive xanthomata, which appeared due to the previously undiagnosed genetic dyslipidemia. Although the relationship between xanthomata, hypertriglyceridemia, and diabetes may be well known in adults, in children, xanthomata are very rarely the presenting feature of diabetes of any cause. The patient was treated with insulin which induced rapid resolution of hypertriglyceridemia and gradual disappearance of xanthomata. This case acknowledges the rarity of diabetes presenting with xanthomata in adolescence, highlights the importance of searching for an underlying dyslipidemia in such a case, and presents diabetes as a long-term complication of acute pancreatitis in children.

Correlation of atherosclerosis between different topographic sites is highly dependent on the type of hyperlipidemia.

There is a surprising paucity of studies that provide quantitative correlative data on the extent of atherosclerosis between different topographic sites. The impact of cardiovascular risk factors is dependent on the vascular bed, which underlies site-selective effects on progression of atherosclerosis. Therefore, the intraindividual correlation of atherosclerosis between different topographic sites may be dependent on the specific cardiovascular risk profile. The focused objective of the current study is to evaluate whether the correlation of the extent of atherosclerosis between different topographic sites is dependent on the type of hyperlipidemia. Atherosclerosis was quantified at four different topographic locations in the aorta of rabbits with type II or type III hyperlipidemia. Correlation coefficients and semi-partial correlation coefficients adjusted for plasma lipoproteins and sex were determined to compare the degree of atherosclerosis at different topographic sites. Semi-partial correlations adjusted for total plasma cholesterol, plasma triglycerides, and sex of the intima/media ratio between different topographic sites were highly dependent on the type of hyperlipidemia. E.g., the semi-partial correlation coefficient between the intima/media ratio at the level of the ascending aorta and at the level of the descending thoracic aorta was 0.87 (p < 0.0001) in the model of type II hyperlipidemia and was only 0.10 (p = NS) in the model of type III hyperlipidemia. This divergent pattern was also observed for other intersite correlations. Semi-partial Pearson correlation coefficients were very similar to unadjusted Pearson correlation coefficients. Correlation of atherosclerosis between different topographic sites may vary importantly in relation to the type of hyperlipidemia.

[Connections between apolipoprotein E genotypes and the development of cardiovascular diseases]. / Az apolipoprotein E genotípusok összefüggése cardiovascularis betegségek kialakulásával.

Elevated plasma lipid level is one of the main risk factors for cardiovascular diseases, which are considered to be primary causes of death. Apolipoprotein E plays a part in the lipid transport in the blood, thus polimophisms of that affect the lipid composition of the plasma. The three most common alleles of apolipoprotein E are e2, e3, e4. Out of the two non-wild type alleles, the e2 and e4, the latter was shown to play a role in the development of cardiovascular diseases and Alzheimer's disease. Some studies mention the e2/e2 homozygote genotype as one of the causes of hyperlipoproteinemia type III. Besides lipid metabolism, apolipoprotein E also influences the manifestation of cardiovascular diseases through other biochemical pathways, therefore it is essential to explore the molecular background of these metabolic pathways.

Dysbetalipoproteinemia Is Associated With Increased Risk of Coronary and Peripheral Vascular Disease.

CONTEXT: Dysbetalipoproteinemia (DBL) is a disorder in which remnant lipoproteins accumulate in the plasma due to a genetic apolipoprotein E dysfunction in conjunction with the presence of secondary metabolic factors. An increased risk of both coronary and peripheral vascular disease (PVD) has been observed in these patients in retrospective studies. OBJECTIVE: The primary objective was to compare the incidence of atherosclerotic cardiovascular disease (ASCVD) and PVD in a cohort of patients with DBL compared with normolipidemic controls. As a secondary objective, the incidence of ASCVD and PVD was compared between patients with DBL and patients with familial hypercholesterolemia (FH). METHODS: A total of 221 patients with DBL, 725 patients with FH, and 1481 normolipidemic controls were included in the study. The data were obtained by review of medical records. RESULTS: In patients with DBL, there was an overall excess risk of PVD (hazard ratio [HR] 13.58, 95% CI 4.76-38.75) and ASCVD (HR 3.55, 95% CI 2.17-5.83) (P < .0001) when compared with normolipidemic controls. When compared with patients with FH, an increased risk of PVD (HR 3.89, 95% CI 1.20-12.55, P = .02) was observed in patients with DBL. CONCLUSION: We demonstrated that the risks of ASCVD and PVD in DBL are >3-fold and >13-fold higher, respectively, than normolipidemic controls. Furthermore, the risk of PVD is ∼4-fold higher in DBL than in FH. Adequate screening of DBL is imperative to improve the clinical care of these patients by preventing the development of ASCVD.

Prospective Registry Study of Primary Dyslipidemia (PROLIPID): Rationale and Study Design.

INTRODUCTION: Primary dyslipidemias are inherited disorders in plasma lipoprotein metabolism that lead to serious cardiovascular and other complications. The Japanese Ministry of Health, Labor and Welfare (MHLW) covers medical expenses, under the Research Program on Rare and Intractable Diseases, for homozygous familial hypercholesterolemia (FH), familial chylomicronemia, sitosterolemia, cerebrotendinous xanthomatosis, lecithin:cholesterol acyltransferase deficiency, Tangier disease, and abetalipoproteinemia. Apolipoprotein A1 deficiency, heterozygous FH, and type III hyperlipoproteinemia are covered by the MHLW Pediatric Chronic Disease Program. Heterozygous FH and type III hyperlipoproteinemia are also important for their relatively common prevalence and, accordingly, high impact on Japanese public health by significant contribution to the overall prevalence of cardiovascular diseases. Therefore, a systemic survey of these diseases is mandatory to estimate their actual situation, such as prevalence, clinical manifestations, and prognoses among the Japanese population. The impact of these rare and intractable diseases on cardiovascular and other complications will likely be higher among Japanese people than other ethnicities because the general Japanese population has many cardioprotective aspects. The current study intends to conduct a multicenter registry of these diseases to assess their demographics and clinical features comprehensively. METHODS AND ANALYSIS: The Prospective Registry Study of Primary Dyslipidemia is a registry-based prospective, observational, multicenter cohort study in Japan, enrolling patients who fulfill the Japanese clinical criteria of the primary dyslipidemias listed above, from 26 participating institutes from August 2015 to March 2023. A total of 1,000 patients will be enrolled in the study and followed for 10 years. Clinical parameters are collected, including physical and laboratory findings, genetic analysis, drugs, lifestyle management, and clinical events, especially cardiovascular events. The primary endpoint of this study is the new onset of cardiovascular disease and acute pancreatitis, and the secondary endpoint is death from any causes. ETHICS AND DISSEMINATION: This study complies with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, and all other applicable laws and guidelines in Japan. The institutional review boards have approved this study protocol at all participating institutes. The final results are to be published at appropriate international conferences and in peer-reviewed journals.

[Orange skin and xanthomas associated with lycopenaemia in a setting of type III dyslipoproteinemia]. / Coloration orangée des téguments et des xanthomes au cours d'une lycopénémie associée à une dyslipoprotéinémie de type III.

BACKGROUND: Type III hyperlipoproteinaemia (HLP) is a rare form of dyslipidaemia characterized by skin lesions such as palmar crease xanthoma and tuberous xanthomas. To our knowledge, there have been no previous reports of yellow-orange discoloration of the skin and xanthomas associated with this disease. CASE REPORT: A 61-year-old woman consulted for palmar crease xanthoma and tuberous xanthomas of the elbows with odd yellow-orange discoloration. Laboratory investigations demonstrated type-III HLP and a high serum lycopene level. After 14 weeks of lipid-lowering treatment, the xanthomas and discoloration showed improvement. In addition, lipid levels and serum lycopene had returned to normal. DISCUSSION: All cases of lycopenaemia reported in the literature followed excessive ingestion of lycopene in foods. We describe the first case of lycopenaemia with orange discoloration of xanthomas following raised serum lycopene but not involving excessive dietary intake. Type-III HLP was doubtless instrumental in the physiopathogenesis of these orange lesions.

Familial apolipoprotein E deficiency.

A unique kindred with premature cardiovascular disease, tubo-eruptive xanthomas, and type III hyperlipoproteinemia (HLP) associated with familial apolipoprotein (apo) E deficiency was examined. Homozygotes (n = 4) had marked increases in cholesterol-rich very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL), which could be effectively lowered with diet and medication (niacin, clofibrate). Homozygotes had only trace amounts of plasma apoE, and accumulations of apoB-48 and apoA-IV in VLDL, IDL, and low density lipoproteins. Radioiodinated VLDL apoB and apoE kinetic studies revealed that the homozygous proband had markedly retarded fractional catabolism of VLDL apoB-100, apoB-48 and plasma apoE, as well as an extremely low apoE synthesis rate as compared to normals. Obligate heterozygotes (n = 10) generally had normal plasma lipids and mean plasma apoE concentrations that were 42% of normal. The data indicate that homozygous familial apoE deficiency is a cause of type III HLP, is associated with markedly decreased apoE production, and that apoE is essential for the normal catabolism of triglyceride-rich lipoprotein constituents.

Case of familial hyperlipoproteinemia type III hypertriglyceridemia induced acute pancreatitis: Role for outpatient apheresis maintenance therapy.

Hypertriglyceridemic pancreatitis (HTGP) accounts for up to 10% of acute pancreatitis presentations in non-pregnant individuals and is the third most common cause of acute pancreatitis after alcohol and gallstones. There are a number of retrospective studies and case reports that have suggested a role for apheresis and insulin infusion in the acute inpatient setting. We report a case of HTGP in a male with hyperlipoproteinemia type III who was treated successfully with insulin and apheresis on the initial inpatient presentation followed by bi-monthly outpatient maintenance apheresis sessions for the prevention of recurrent HTGP. We also reviewed the literature for the different inpatient and outpatient management modalities of HTGP. Given that there are no guidelines or randomized clinical trials that evaluate the outpatient management of HTGP, this case report may provide insight into a possible role for outpatient apheresis maintenance therapy.

Effects of fenofibrate on apolipoprotein kinetics in patients with coexisting dysbetalipoproteinemia and heterozygous familial hypercholesterolemia.

Dysbetalipoproteinemia (dysb) and familial hypercholesterolemia (FH) are two genetic disorders giving rise to severe disturbances of lipid homeostasis and premature atherosclerosis. The co-occurrence of both metabolic abnormalities is very rare and is estimated to affect 1 individual per 2,500,000 in the general population. However, the relative contribution of these two dyslipidemias to the combined lipoprotein phenotype is unknown. The two objectives of this study were (1) to compare the in vivo kinetics of triglyceride-rich lipoprotein (TRL) apolipoprotein (apo) B48, VLDL, IDL and LDL apo B100 as well as plasma apo A-l labelled with a stable isotope (l-(5,5,5-D3) leucine) in two subjects presenting both heterozygous FH and dysbetalipoproteinemia (FH+/dysb+), in six FH heterozygotes and in five normolipidemic controls, and (2) to examine the impact of a 6-week treatment with micronized fenofibrate 200 mg/d on apolipoprotein kinetics in FH+/dysb+. As compared with FH heterozygotes and controls, the two FH+/dysb+ subjects showed elevated TRL apo B48 and VLDL, IDL apo B100 pool sizes (PS) mainly due to lower fractional catabolic rates (FCR). Moreover, as compared with FH heterozygotes, FH+/dysb+ subjects presented lower LDL apo B100 PS due to a higher FCR. Pool size, FCR and production rate (PR) of apo A-l were higher in FH+/dysb+ subjects than in FH heterozygotes. In FH+/dysb+ subjects, fenofibrate treatment was associated with a decreased TRL apo B48 PS (-52 and -61%), VLDL apo B100 (-61 and -63%) and IDL apo B100 (-37 and -16%) and an increased FCR of TRL apo B48 (10 and 67%), VLDL apo B100 (123 and 57%) and IDL apo B100 (29 and 10%). Fenofibrate also increased LDL apo B100 PS (3 and 57%) due to an increase in PR (80 and 26%) but had divergent effects on LDL apo B100 FCR. These results indicate that the coexistence of dysbetalipoproteinemia and heterozygous FH results in a mixed lipoprotein phenotype that is intermediate between the two pure phenotypes and that fenofibrate treatment partially reverses lipoprotein abnormalities, mostly through changes in PR and FCR of apo B48- and B100-containing lipoproteins.

Clomiphene-associated combined hyperlipidemia: a case report.

BACKGROUND: Hyperlipidemia associated with clomiphene use is an uncommon but potentiallly serious complication of this therapy. Clomiphene is structurally similar to other synthetic estrogen analogs, which are known to induce marked hypertriglyceridemia. There is a paucity of data regarding the effects of clomiphene on lipid metabolism in humans. CASE: A 33-year-old woman with obesity, polycystic ovary syndrome and a long history of amenorrhea was treated with clomiphene therapy to induce ovulation. Baseline lipids were suggestive of an underlying lipid disorder, but there was a marked deterioration in her lipid profile in association with the use of clomiphene. On cessation of the clomiphene therapy her lipid profile slowly improved, and specific lipid-lowering therapy was not used. Further investigation for the possibility of an underlying lipid disorder confirmed the diagnosis of familial dysbetalipoproteinemia. CONCLUSION: Clomiphene should be used cautiously in women known to have dyslipidemia. We recommend that patients with predisposing risk factors have their lipids measured prior to ovulation induction with clomiphene.

[Apolipoprotein E deficiency associated with type III hyperlipoproteinemia--analysis of apolipoprotein E].

CASE REPORT: The patient was a 50-year old male who was found to have a high cholesterol level during a routine health check up at work 5 years before and was examined at Keio University Hospital. Lipoprotein electrophoresis on agarose gel revealed type III hyperlipidemia, and a screening test yielded the following values (mg/dl): total cholesterol, 420; TG, 138; and HDL-cholesterol, 105. Turbidimetric immunoassay showed that the apolipoprotein E (apoE) level was below the limit of detection. Since he was 25 years old, the patient had sometimes noticed xanthomas on his knees and eyelids, and for that reason we made a diagnosis of apoE deficiency associated with type III hyperlipidemia. We tried using SDS-polyacrylamide gel electrophoresis, Western blot, and the protein chip method to detect apoE in this case, but the level was below the limit of detection by the first two methods, and it was so low that it was detected near the sensitivity limit of the protein chip method. Diet therapy, statin therapy, and fibrate therapy have been continued, and the latest data are: total cholesterol, 373; TG, 95; and HDL-cholesterol, 83. No manifestations associated with arteriosclerotic disease other than mild xanthomas have been observed.

High frequency of Fredrickson's phenotypes IV and IIb in Brazilians infected by human immunodeficiency virus.

BACKGROUND: Human immunodeficiency virus (HIV) infection is very prevalent in Brazil. HIV therapy has been recently associated with coronary heart disease (CHD). Dyslipidemia is a major risk factor for CHD that is frequently described in HIV positive patients, but very few studies have been conducted in Brazilian patients evaluating their lipid profiles. METHODS: In the present work, we evaluated the frequency and severity of dyslipidemia in 257 Brazilian HIV positive patients. Two hundred and thirty-eight (93%) were submitted to antiretroviral therapy (224 treated with protease inhibitors plus nucleoside reverse transcriptase inhibitors, 14 treated only with the latter, 12 naive and 7 had no records of treatment). The average time on drug treatment with antiretroviral therapy was 20 months. None of the patients was under lipid lowering drugs. Cholesterol, triglyceride, phospholipid and free fatty acids were determined by enzymatic colorimetric methods. Lipoprotein profile was estimated by the Friedewald formula and Fredrickson's phenotyping was obtained by serum electrophoresis on agarose. Apolipoprotein B and AI and lipoprotein "a" were measured by nephelometry. RESULTS: The Fredrickson phenotypes were: type IIb (51%), IV (41%), IIa (7%). In addition one patient was type III and another type V. Thirty-three percent of all HIV+ patients presented serum cholesterol levels >or= 200 mg/dL, 61% LDL-cholesterol >or= 100 mg/dL, 65% HDL-cholesterol below 40 mg/dL, 46% triglycerides >or= 150 mg/dL and 10% have all these parameters above the limits. Eighty-six percent of patients had cholesterol/HDL-cholesterol ratio >or= 3.5, 22% increased lipoprotein "a", 79% increased free fatty acids and 9% increased phospholipids. The treatment with protease inhibitors plus nucleoside reverse transcriptase inhibitors increased the levels of cholesterol and triglycerides in these patients when compared with naïve patients. The HDL-cholesterol (p = 0.01) and apolipoprotein A1 (p = 0.02) levels were inversely correlated with the time of protease inhibitor therapy while total cholesterol levels had a trend to correlate with antiretroviral therapy (p = 0.09). CONCLUSION: The highly varied and prevalent types of dyslipidemia found in Brazilian HIV positive patients on antiretroviral therapies indicate the urgent need for their early diagnosis, the identification of the risk factors for CHD and, when needed, the prompt intervention on their lifestyle and/or with drug treatment.

Unmasking of type III hyperlipoproteinemia by hypothyroidism: a dramatic illustration of altered lipoprotein metabolism in a postpartum woman.

OBJECTIVE: To illustrate the potential abnormalities in lipoprotein metabolism associated with type III hyper-lipoproteinemia and the modulation of their clinical expression by thyroid hormone and estrogenic status. METHODS: An illustrative case, with associated clinical and laboratory data, is presented, and relevant clinical and pathophysiologic studies from the literature are reviewed. RESULTS: A 35-year-old woman, at 7 months after delivery of her first child, presented to her family physician with a complaint of painful eruptions on the palms of her hands. On evaluation, she was found to have new hypothyroidism and severe hypertriglyceridemia (>1,569 mg/dL). Thyroxine replacement was initiated, and she was referred to the lipid clinic. When seen in the lipid clinic shortly thereafter, her triglyceride level had normalized, but her low-density lipoprotein (LDL) fraction was strikingly elevated (representing a combination of elevated intermediate-density lipoprotein and LDL cholesterol). On physical examination, palmar xanthomas were noted, suggestive of type III hyperlipoproteinemia. This diagnosis was further supported by homozygosity at the apolipoprotein E (apo E) gene locus for the apo E2 allele implicated in this condition. Ultimately, with attainment of euthyroidism in the subsequent weeks, the lipid profile normalized, with the LDL cholesterol concentration particularly reduced at 55 mg/dL. CONCLUSION: Clinical expression of type III hyperlipoproteinemia necessitates interaction between an underlying genetic defect of lipoprotein metabolism (apo E2 homozygosity) and a secondary metabolic insult such as, in the current case, hypothyroidism and possibly breast-feeding-mediated hypoestrogenemia. As such, in patients with type III hyperlipoproteinemia, it is essential to search for exacerbating factors, particularly because the amelioration of such factors may rectify the effects of the underlying dyslipidemia.

Primary hypertriglyceridemia in children and adolescents.

Primary disorders of lipid metabolism causing hypertriglyceridemia (HyperTG) result from genetic defects in triglyceride synthesis and metabolism. With the exception of lipoprotein lipase deficiency, these primary HyperTG disorders usually present in adulthood. However, some are unmasked earlier by precipitating factors, such as obesity and insulin resistance, and can be diagnosed in adolescence. Physical findings may be present and can include eruptive, palmer, or tuberoeruptive xanthomas. Triglyceride levels are very high to severe and can occur in the absence or the presence of other lipid abnormalities. Each of the causes of HyperTG is associated with an increased risk to develop recurrent pancreatitis and some may increase the risk of premature cardiovascular disease. Adoption of a healthy lifestyle that includes a low-fat diet, optimizing body weight, smoking avoidance/cessation, and daily physical activity is the first line of therapy. Pharmacologic therapies are available and can be beneficial in select disorders. Here, we review the causes of primary HyperTG in children and adolescents, discuss their clinical presentation and associated complications including the risk of pancreatitis and premature cardiovascular disease, and conclude with management and novel therapies currently in development. The goal of this article is to provide a useful resource for clinicians who may encounter primary HyperTG in the pediatric population.

Increased frequency of lipoprotein disorders similar to type III hyperlipoproteinemia in survivors of myocardial infarction in Japan.

We have investigated serum lipids, lipoproteins and apolipoprotein levels in 97 survivors of acute myocardial infarction in order to clarify the characteristics of lipid and lipoprotein disorders in coronary artery disease among Japanese. Although the HDL cholesterol level was lower and the atherogenic index was higher in the myocardial infarction (MI) group than in the control group, in agreement with previous papers, there was no significant difference in total serum cholesterol level between the MI and the control groups. On the other hand, the triglyceride level was significantly higher in the MI group. The MI group also had higher levels of both cholesterol and triglyceride in the VLDL fraction (d less than 1.006) with a statistically significant increase in the ratio of cholesterol to triglyceride compared with the control group. Levels of both lipids in the IDL fraction (1.006 less than d less than 1.019) were higher in the MI group than in the control group. Lipoprotein analysis with PAG disc electrophoresis revealed a more frequent occurrence of a "midband", which appeared as an additional band between the LDL and VLDL positions, in the MI group than in the control group (MI:51% versus control: 25%, P less than 0.02). The midband-positive subgroup had a higher ratio of cholesterol to triglyceride in the VLDL fraction and higher levels of both lipids in the IDL fraction. Isoelectric focusing of apo VLDL revealed that the incidence of the suspected apo E-ND (E3/2 or E4/2) constitution, which was determined by a low ratio (less than 1.1) of the peak area of E3 to that of E2, was three times higher in the MI group than in the control group (MI:25% versus control: 7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of plasmapheresis on familial type III hyperlipoproteinemia associated with glomerular lipidosis, nephrotic syndrome and diabetes mellitus.

A 59-year-old woman, one of 5 cases with familial type III hyperlipoproteinemia reported at our clinic to date, had nephrotic syndrome and diabetes mellitus, but had neither coronary atherosclerosis nor xanthoma. A renal biopsy specimen revealed a massive cluster of foam cells containing apolipoprotein B and E in the mesangial region of the kidney. A restricted diet intake combined with lipid-lowering drugs such as cholestyramine, clinofibrate, and bezafibrate, in addition to methylprednisolone was not very effective in lowering serum triglyceride and cholesterol levels within physiological ranges. Therefore, plasmapheresis, using a dextran sulfate-cellulose column, was performed. Repeated plasmapheresis resulted in a marked decrease in both serum total cholesterol and triglyceride. A second renal biopsy specimen performed 2 years later revealed a marked reduction in foam cells with concurrent improvement in her nephrotic syndrome and glucose intolerance. These results suggest that familial type III hyperlipoproteinemia may be responsible for glomerular lipidosis resulting in nephrotic syndrome. They also indicate that plasmapheresis using a dextran sulfate-cellulose column is very effective in the removal of abnormal lipoproteins such as beta-very low density lipoprotein and intermediate density lipoprotein in a case of familial type III hyperlipoproteinemia.