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Chylomicron retention disease is a recessive inherited disorder characterized by fat malabsorption and steatorrhea and is associated with failure to thrive in infancy. We describe a kindred carrying a mutation of Sara2 gene causing a chylomicron retention phenotype. The proband was a 5-month-old baby, born of consanguineous, apparently healthy parents from Morocco, with failure to thrive. There was a large quantity of fats in feces and malabsorption of fat-soluble vitamins. Intestinal biopsies showed a diffused enterocyte vacuolization with large cytosolic lipid droplets. Chylomicron retention disease or Anderson disease was hypothesized, and the Sara2 gene was analyzed by direct sequencing. Analysis of the Sara2 gene in the proband identified a 2-nucleotide homozygous deletion in exon 3 leading to a premature stop codon (c.75-76 del TG-L28fsX34). The father was heterozygous for the same mutation, whereas the proband's mother was homozygous, suggesting a variable phenotypic expression of the molecular defect. More studies are needed to understand the reasons of the phenotypic variability of the same molecular defect in the same family., (Copyright 2010 Elsevier Inc. All rights reserved.)

Triglyceride-rich lipoproteins generated during the postprandial phase are atherogenic. Large very low-density lipoproteins (LDLs) or chylomicrons (CMs) are not as atherogenic as their remnants (Rem). Small and dense LDLs are associated with cardiovascular disease. Low-density lipoprotein size is partly under genetic control and is considered as a relatively stable LDL feature. In this article, we present data on retinyl palmitate kinetics correlated with the modification of LDL features in terms of size, density, and in vitro receptor binding affinity after an oral fat load. Six nondiabetic, hypertriglyceridemic (HTG) patients and 6 healthy controls were examined. Low-density lipoprotein size was assessed by gradient gel electrophoresis, and LDL density by density gradient ultracentrifugation. Low-density lipoprotein binding affinity was tested by in vitro competition binding assay on normal human skin fibroblasts (HSFs) and hepatoma cells (HepG2). Kinetic parameters were estimated in CM and Rem fractions by compartmental modeling. Hypertriglyceridemic patients showed significantly higher triglyceride area and a slower CM fractional catabolic rate. Postprandial LDL density increased both in HTG patients and in the control group with a significant difference between groups at 6 hours. Fasting LDL size was lower in HTG patients vs controls but decreased similarly in the postprandial phase. Low-density lipoprotein size and density postprandial modifications were not correlated with any investigated parameter. Postprandial LDLs were internalized more efficiently by HSF than baseline LDL only in the HTG group. In conclusion, postprandial LDLs are smaller and denser compared with fasting LDLs after an oral fat load. Postprandial LDLs also slightly increased their affinity to the HSF cell receptors.

Triglycerides (TGs) are vehicled by multiple particles with different abilities to promote atherosclerosis. Among plasma TG-rich lipoproteins (TRLs), subspecies may or may not contain apolipoprotein E (apoE) molecules: in this study, we evaluated the relative contribution of apoE-rich and apoE-poor TRLs to coronary atherosclerosis. We selected a group of males with premature coronary artery disease (CAD) without any of the classical nonlipid risk factors and/or high plasma lipid levels and evaluated the plasma concentration of TRL subspecies in comparison with healthy controls. Patients with CAD and controls had total cholesterol and TG levels within the normal range (despite slightly, even if significantly, higher TG levels in patients with CAD) and low-density lipoprotein cholesterol levels near optimal values. Nevertheless, patients with CAD had significantly lower high-density lipoprotein cholesterol, smaller low-density lipoprotein peak particle size, and a reduced HDL2b subfraction than controls. In addition, we observed higher concentrations of total TRL in patients with CAD together with a selective increase in apoE-rich particles. All these data were confirmed after correction for TG levels. We also investigated which parameters were associated with the spread of coronary atherosclerosis. Subjects with a single-vessel disease had selectively lower levels of apoE-rich fractions than patients with a multivessel disease. This was confirmed by multivariate analysis. Patients with a premature CAD free of nonlipid conventional risk factors, despite not having elevated lipid levels, show several lipoprotein abnormalities. Besides known atherogenic alterations, the accumulation of apoE-rich TRL subfractions may represent an additive factor that can potentially promote and initiate the atherosclerotic process.

Thyroid status in humans is an important factor in the regulation of lipoprotein metabolism. There are several data on hypothyroidism in the adult population, but less information is available about congenital hypothyroidism. Since lipid metabolism at birth is substantially different from that of adults, it is not likely that the same abnormalities that occur in adult hypothyroidism are also present when this is diagnosed at early life. We studied 16 subjects with congenital hypothyroidism, seven at the time of diagnosis and also after normalization of thyroid hormone levels over a period of 2.0 +/- 1.0 months of substitution therapy with L-thyroxine (5.9 +/- 1.2 micrograms/kg/d) and nine already on L-thyroxine therapy for a period of 4.7 +/- 3.2 months. Thirty-nine apparently healthy subjects matched for age were selected as controls. In all subjects, total cholesterol (CHO), triglycerides (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol (HDL-C), apolipoproteins (apo) A-I and B, lipoprotein(a) [Lp(a)] thyrotropin (TSH), (LDL-C), total and free thyroxine (T4), and triiodothyronine (T3) were determined. CHO, HDL-C, and apo A-I levels were significantly higher in patients at the time of diagnosis than in controls (respectively, P = .0079, .0007, and .0004), whereas TG, LDL-C, apo B, and Lp(a) levels were not significantly different. During L-thyroxine substitution therapy in these subjects, HDL-C and apo A-I levels significantly decreased (respectively, by a mean of -36.2% and -24.4%), with similar behavior in all subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty-three patients with chronic renal failure (CRF) and uremic hypertriglyceridemia (HTG) on hemodialysis were compared with 33 type IV hyperlipoproteinemic patients matched for age, body mass index (BMI), and triglyceride (TG) levels. The two forms of hypertriglyceridemia showed different apolipoprotein profiles: apo AI, AII, and B levels and apo CII:CIII and TG:apo CIII ratios of CRF-HTG patients were lower and apo CIII levels were higher than the levels of type IV subjects.