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Chylomicronemia is characterized by severe hypertriglyceridemia when chylomicrons persist in plasma despite a fasting state. The recessive monogenic form is due to homozygous or compound heterozygous loss-of-function mutations in ...
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Chylomicronemia is characterized by severe hypertriglyceridemia when chylomicrons persist in plasma despite a fasting state. The recessive monogenic form is due to homozygous or compound heterozygous loss-of-function mutations in the LPL gene or genes involved in the assembly, transport, or function of LPL, including APOC2, APOA5, GP1HBP1 , and LMF1. The multifactorial form of chylomicronemia is due to both common small-effect variants and rare heterozygous large-effect variants in genes in which mutations are associated secondarily with hypertriglyceridemia. The combined inheritance of these variants increases susceptibility to chylomicronemia, and the number of hypertriglyceridemia-associated alleles carried by an individual represents a genetic or polygenic triglyceride risk score. Among these genes associated with hypertriglyceridemia is PPARG . PPAR gamma is a nuclear transcription factor encoded by the PPARG gene expressed predominantly in adipocytes that is involved in glucose, lipid, and adipose tissue metabolism. Known rare mutations and common polymorphisms in the PPARG genes are associated with a broad range of clinical phenotypes, including hypertriglyceridemia. Here, we present multiple family members with a novel heterozygous PPARG mutation that has not been previously reported. (C) 2021 National Lipid Association. Published by Elsevier Inc. All rights reserved.
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Gpihbp1-deficient mice exhibit severe chylomicronemia, even on a low-fat diet, with grossly lipemic plasma and plasma triglyceride levels as high as 5000 mg/dl. GPIHBP1 is expressed on the luminal surface of endothelial cells of h...
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Gpihbp1-deficient mice exhibit severe chylomicronemia, even on a low-fat diet, with grossly lipemic plasma and plasma triglyceride levels as high as 5000 mg/dl. GPIHBP1 is expressed on the luminal surface of endothelial cells of heart, muscle and fat, precisely where the lipolytic processing of triglyceride-rich lipoproteins occurs. When GPIHBP1 is expressed in cultured cells, it confers upon those cells the capacity to bind both chylomicrons and lipoprotein lipase, suggesting that GPIHBP1 is a key platform for the lipolytic processing of chylomicrons in capillaries. These cell culture and mouse studies suggested the possibility that some cases of hypertriglyceridemia in humans might be caused by defects in GPIHBP1. In a recent study, the exons of GPIHBP1 were sequenced in 160 patients with severe hypertriglyceridemia, and a homozygous G56R mutation was identified in two siblings with chylomicronemia. This mutation was not encountered in 600 normolipidemic Caucasian control subjects or 610 Caucasian patients with hyperlipidemia. Although the finding of a homozygous GPIHBP1 mutation in two siblings was intriguing, recent cell culture studies have suggested that the G56R mutation may not alter GPIHBP1 function. Additional sequencing efforts in diverse populations will be required to understand the relevance of GPIHBP1 mutations to human hypertriglyceridemia.
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PURPOSE To report a case of lipemia retinalis in a patient with diabetes. CASE SUMMARY: A 27-year-old female with type 2 diabetes visited our clinic with visual disturbance in her left eye while being followed up from a pars plana...
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PURPOSE To report a case of lipemia retinalis in a patient with diabetes. CASE SUMMARY: A 27-year-old female with type 2 diabetes visited our clinic with visual disturbance in her left eye while being followed up from a pars plana vitrectomy in her right eye for proliferative diabetic retinopathy. On fundus examination of both eyes, the retinal vessels were creamy white and the retinal veins were undistinguishable from the retinal arteries. The serum triglyceride level was 2,676 mg/dL. The patient was asymptomatic except for visual impairment due to vitreous hemorrhage in her left eye. The patient was diagnosed with lipemia retinalis and chylomicronemia syndrome. After controlling the triglyceride level, funduscopic findings in the both eyes were improved. However, the visual acuity in her right eye remained unchanged. CONCLUSIONS: Lipemia retinalis can be a sign of a systemic condition although it may not affect visual acuity. Fundus examination may be a useful tool in the early diagnosis of hyperlipidemia.
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Hypertriglyceridemia is a rare disorder in childhood. Familial Chylomicronemia Syndrome (FCS) is a rare genetic disease that leads to severe hypertriglyceridemia, often associated with recurrent episodes of pancreatitis. In this s...
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Hypertriglyceridemia is a rare disorder in childhood. Familial Chylomicronemia Syndrome (FCS) is a rare genetic disease that leads to severe hypertriglyceridemia, often associated with recurrent episodes of pancreatitis. In this syndrome, traditional lipid-lowering drugs are marginally effective. A 6-months-old infant with complaints of recurrent episodes of abdominal colic and pancreatitis, with S. Cholesterol 552?mg% and Triglycerides 6400?mg%, was treated with Ayurvedic medicines. After six months of medication, Serum Cholesterol levels were within normal limits, and within the three years of regular treatment, S. Triglycerides was under 2000?mg%. Recurrent episodes of acute abdominal colic and vomiting reduced significantly. The patient was treated for Kapha Pitta dushti in Rasa and Raktavah srotas (deformity of the Kapha Pitta humors in the tissue nourishment pathway of the first and the second tissue respectively). Laghoo Sootshekhar, Arogyavardhini, Tinospora cordifolia , Cyprus rotundus, Aegle marmelos , Berberis aristata , Vettiveria zizanioides , and Triphala were the medicines used frequently. The three years treatment was safe and effective. Cost-effectiveness was an added feature of this treatment. Clinical experience of this case shows that congenital hyperlipidemia can manage by Ayurvedic medicine.
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Multifactorial chylomicronemia syndrome (MCS or type V hyperlipoproteinemia) is the most frequent cause of severe hypertriglyceridemia and is associated with an increased risk of acute pancreatitis, cardiovascular disease, and non...
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Multifactorial chylomicronemia syndrome (MCS or type V hyperlipoproteinemia) is the most frequent cause of severe hypertriglyceridemia and is associated with an increased risk of acute pancreatitis, cardiovascular disease, and non-alcoholic steatohepatitis. The estimated prevalence of MCS in the North American population is 1:600–1:250 and is increasing due to the increasing prevalence of obesity, metabolic syndrome, and type 2 diabetes. Differentiating between familial chylomicronemia syndrome and MCS is crucial due to their very different treatments. In recent years, several cohort studies have helped to differentiate these two conditions, and recent evidence suggests that MCS itself is a heterogeneous condition. This mini-review will summarize recent literature on MCS, with a specific focus on the genetic determinants of the metabolic risk and the latest developments concerning the pharmacological and non-pharmacological treatment options for these patients. Possible research directions in this field will also be discussed.
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BACKGROUND: Chylomicronemia syndrome (CS) is a metabolic condition characterized by severely elevated plasma triglycerides (>880 mg/dL) and high rates of morbidity and mortality. The syndrome can be classified into two major group...
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BACKGROUND: Chylomicronemia syndrome (CS) is a metabolic condition characterized by severely elevated plasma triglycerides (>880 mg/dL) and high rates of morbidity and mortality. The syndrome can be classified into two major groups: monogenic familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS), the frequencies of which are ill-defined.
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Familial chylomicronemia is caused by deficiency of lipoprotein lipase or its co-activators. Here, we report an infant with apolipoprotein C-II (APOC2) deficiency, who developed acute pancreatitis 37 days after birth. He presented...
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Familial chylomicronemia is caused by deficiency of lipoprotein lipase or its co-activators. Here, we report an infant with apolipoprotein C-II (APOC2) deficiency, who developed acute pancreatitis 37 days after birth. He presented as abdominal sepsis with fever, irritability and abdominal distention. Amylase levels were low, but lipase levels and imaging findings were consistent with acute pancreatitis. He had severe hypertriglyceridemia (1091 mg/dl). Keeping him nil orally for two days resulted in rapid decrease in triglyceride levels and resolution of the clinical findings. APOC2 gene sequencing revealed a homozygous splice-site mutation (c.55 + 1G > C). To the best of our knowledge, this patient is not only the youngest reported patient with APOC2 deficiency, but also the youngest such patient who developed pancreatitis. Although he had a severe presentation, invasive methods to treat hypertriglyceridemia were not necessary. We emphasize that clinical findings and amylase levels are not reliable to diagnose pancreatitis in this age group. (C) 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.
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Abstract Type V hypertriglyceridemia in children is a rare condition since it has often been associated with obesity, type II diabetes, metabolic syndrome and hormone therapy. We encountered a case of massive hypertriglyceridemia ...
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Abstract Type V hypertriglyceridemia in children is a rare condition since it has often been associated with obesity, type II diabetes, metabolic syndrome and hormone therapy. We encountered a case of massive hypertriglyceridemia (1900?mg/dl) in a 6?years old boy with complains of acute pancreatitis but no physical manifestations. There was no family history of sudden cardiac death, father and younger male sibling were found to be normal. The mother however had hypertriglyceridemia. The child was managed by dietary changes, omega 3 capsules and low dose fenofibrate. On follow up showed there was reduction in lipid profile and lipoprotein electrophoretic pattern showed bands for VLDL and chylomicron indicating type V hyperlipidemia. Early diagnosis via screening for lipid profile of such patients and their family can improve prognosis and quality of life of these children.
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Severe hypertriglyceridemia (HTG), characterized by triglycerides (TG) permanently over 10 mmol/L, may correspond to familial chylomicronemia syndrome (FCS), a rare disorder. However, hypertriglyceridemic patients more often prese...
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Severe hypertriglyceridemia (HTG), characterized by triglycerides (TG) permanently over 10 mmol/L, may correspond to familial chylomicronemia syndrome (FCS), a rare disorder. However, hypertriglyceridemic patients more often present multifactorial chylomicronemia syndrome (MCS), characterized by highly variable TG. A few nonsense variants of LMF1 gene were reported in literature in FCS patients. In this study, we described a woman with an intermittent severe HTG. NGS analysis and the sequencing of a long range PCR product revealed a homozygous deletion of 6507 base pairs in LMF1 gene, c.730-1528_898-3417del, removing exon 6, predicted to create an in-frame deletion of 56 amino acids, p.(Thr244_Gln299del). Despite an exon 6 homozygous deletion of LMF1, the patient's highly variable lipid phenotype was suggestive of MCS diagnosis. (C) 2020 National Lipid Association. All rights reserved.
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Context Differentiation between familial chylomicronemia syndrome (FCS, type 1 hyperlipoproteinemia), a rare metabolic disorder, and the more common multifactorial severe hypertriglyceridemia (sHTG, type 5 hyperlipoproteinemia) is...
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Context Differentiation between familial chylomicronemia syndrome (FCS, type 1 hyperlipoproteinemia), a rare metabolic disorder, and the more common multifactorial severe hypertriglyceridemia (sHTG, type 5 hyperlipoproteinemia) is challenging because of their overlapping symptoms but important in patient management. Objective To assess whether readily obtainable clinical information beyond triglycerides can effectively diagnose and differentiate patients with FCS from those with sHTG, based on well-curated data from two intervention studies of these conditions. Methods The analysis included 154 patients from two phase 3 clinical trials of patients with sHTG, one cohort with genetically confirmed FCS (n = 49) and one with multifactorial sHTG (n = 105). Logistic regression analyses were performed to determine the ability of variables (patient demographics, medical history, and baseline lipids, individually or in sets) to differentiate the patient populations. Receiver operating characteristics were used to determine the variable sets with the highest accuracy (percentage of times actual values matched predicted) and optimal sensitivity and specificity. Results The primary model diagnosed 45 of 49 patients with FCS and 99 of 105 patients with sHTG correctly. Optimal sensitivity for all available parameters (n = 17) was 91.8%, optimal specificity was 94.3%, and accuracy was 93.5%. Fasting low-density lipoprotein cholesterol (LDL-C) provided the highest individual predictability. However, a three-variable set of ultracentrifugally measured LDL-C, body mass index, and pancreatitis history differentiated the diseases with a near similar accuracy of 91.0%, and adding high-density lipoprotein cholesterol and very low-density lipoprotein cholesterol for a five-variable set provided a small incremental increase in accuracy (92.2%). Conclusions In the absence of genetic testing, hypertriglyceridemic patients with FCS and sHTG can be differentiated with a high degree of accuracy by analyzing readily obtainable clinical information.
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