[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.

Severe hypercholesterolemia associated with decreased hepatic triglyceride lipase activity and pseudohyponatremia in patients after allogeneic stem cell transplantation.

A 55-year-old woman with Ph-negative acute lymphoblastic leukemia in primary induction failure received allogeneic peripheral blood stem cell transplantation from her HLA-compatible sister. Pseudohyponatremia developed due to extreme hypercholesterolemia of 4091 mg/dL accompanied by lipoprotein X and lipoprotein Y. The hypercholesterolemia was caused by cholestasis due to chronic GVHD and ischemic cholangiopathy. In addition, we found that hepatic triglyceride lipase (HTGL) activity was severely decreased, which could be another novel factor causing extreme hypercholesterolemia after allogeneic transplantation. The total cholesterol has been gradually decreasing followed by the improvement of cholestasis with bezafibrate, ursodeoxycholic acid and prednisone treatments, and by a slight increase in HTGL-protein. To our knowledge, this is the first report to describe the association of decreased HTGL with extreme hypercholesterolemia after allogeneic transplantation.

[Analysis of small dense LDL in patients with type 2 diabetic mellitus by the modified Krauss method using an internal standard].

In patients with Type 2 diabetes mellitus (Type 2 DM), the relationship between the prevalence rate of small dense LDL (sdLDL) and parameters of lipid metabolism was analyzed using the method devised by modified Krauss method using apoferritin as an internal standard. The prevalence rate of sdLDL was 34% compared with it of normal subjects in this study. When the severity of Type 2 DM was classified into three groups of the HbA1c value, neither the sdLDL size nor its prevalence rate differed significantly depending upon the severity of the Type 2 DM. Also, when the prevalence rate of sdLDL was analyzed in relation to the severity of complications, i.e., of microangiopathy (retinopathy and nephropathy) or macroangiopathy (cerebral infarction), there was no significant difference in the prevalence rate of sdLDL depending on the severity of any of these complications. On the other hand, the prevalence rate of sdLDL was found to be correlated with the serum TG level. The serum level of TG-rich remnants (metabolites of TG) was also high in patients with sdLDL. It should take notice that the assessment of sdLDL should be used the authorized method for the evaluation. Thus it is concluded that the levels of sdLDL were important in evaluation of Type 2 DM. The prevalence rate of sdLDL did not correlate with the severity, nor the modalities for the complications of Type 2 DM.

Simplified method for the diameter sizing of serum low-density lipoprotein using polyacrylamide gradient gel electrophoresis.

The appearance of small, dense, low-density lipoprotein in serum has been demonstrated to be associated with increased risk of coronary artery disease. The molecular diameter of low-density lipoprotein is usually measured on the basis of mobility differences on polyacrylamide gel electrophoresis. However, since mobility assessed by this method is seriously affected by the increased levels of serum free fatty acids associated with hypertriglyceridemia, we used polyacrylamide gradient gel electrophoresis to eliminate the interference by fatty acids and devised a simple, precise method of polyacrylamide gradient gel electrophoresis to measure the diameter of small, dense, low-density lipoproteins in serum. We used apoferritin and thyroglobulin, which have a molecular diameter of 12.2 nm and 17.0 nm, respectively, and standard low-density lipoprotein particles having a diameter of 25.7 and 27.0 nm as calibrators, estimated by measurement of negative staining of electron microscopy. We also included apoferritin as an internal standard for polyacrylamide gradient gel electrophoresis. The only stain used was Coomassie brilliant blue, and it was used for lipoprotein staining. When we used low-density lipoprotein of 25.73 nm in diameter as a quality control specimen, the coefficient of variation of the size measurements obtained by our method was less than 1.2%. The new method markedly improved the laboratory procedure for measuring the diameter of low-density lipoproteins.

Abetalipoproteinemia-like lipid profile and acanthocytosis in a young woman with anorexia nervosa.

We report the case of a 17-year-old woman with anorexia nervosa (AN) who developed an abetalipoproteinemia-like lipid profile and acanthocytosis. These abnormalities resolved slowly as her nutritional status improved. We considered 3 possible causes of an abetalipoproteinemia-like lipid profile in AN: (1) depletion of hepatic substrate for apolipoprotein B synthesis, (2) lack of exogenous fatty acids with exhaustion of endogenous stores of triglycerides in adipose tissue, and (3) preservation of the lipoprotein lipase (LPL) mass. This unusual case provides important clues that enhance our understanding of lipid metabolism under exogenous and endogenous fat deprivation and highlights the pivotal role of LPL as a gatekeeper of the energy source.