chylomicronemia syndrome

Familial chylomicronemia syndrome (FCS) is a rare lipid disorder posing significant clinical burdens on patients. Due to its rarity, variety of presentations, and lack of universal diagnostic criteria, patients see an average of five physicians before diagnosis. We screened adults for a triglyceride level ≥1000 mg/dL from September 2015 to September 2016 and a history of pancreatitis and performed a thorough chart review on those who met the criteria. An adjudication panel used a definition that also called for supportive information including history of hypertriglyceridemia or family history of pancreatitis/hypertriglyceridemia...

The intravascular processing of triglyceride-rich lipoproteins depends on lipoprotein lipase (LPL) and GPIHBP1, a membrane protein of endothelial cells that binds LPL within the subendothelial spaces and shuttles it to the capillary lumen. In the absence of GPIHBP1, LPL remains mislocalized within the subendothelial spaces, causing severe hypertriglyceridemia (chylomicronemia). The N-terminal domain of GPIHBP1, an intrinsically disordered region (IDR) rich in acidic residues, is important for stabilizing LPL's catalytic domain against spontaneous and ANGPTL4-catalyzed unfolding...

BACKGROUND: Volanesorsen, an investigational inhibitor of apoC-III synthesis, significantly reduced triglyceride levels in clinical trials in patients with familial chylomicronemia syndrome (FCS), a rare genetic disorder characterized by marked chylomicronemia leading to a spectrum of symptoms, including recurrent abdominal pain and episodes of potentially fatal acute pancreatitis (AP). OBJECTIVE: To determine the effect of volanesorsen on burden of disease on patients with FCS Methods: ReFOCUS was a retrospective global web-based survey open to patients with FCS who received volanesorsen for ≥3 months in an open-label extension study...

A spectrum of disorders, ranging from rare severe cases of homozygous null lipoprotein lipase deficiency (LPLD) -familial chylomicronemia syndrome (FCS) to heterozygous missense LPLD or polygenic causes, result in hypertriglyceridemia and pancreatitis. The effects of mutations are exacerbated by environmental factors such as diet, pregnancy and insulin resistance. Areas covered: In this review, authors discuss chronic treatment of FCS by ultra-low fat diets allied with the use of fibrates, omega-3 fatty acids, niacin, statins and insulin-sensitising therapies depending on the extent of residual LPL activity; novel therapies in development target triglyceride-rich lipoprotein particle clearance...

BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder with loss of function mutations of lipoprotein lipase resulting in hypertriglyceridemia and accumulation of chylomicrons in plasma, often leading to acute pancreatitis. The mainstay of treatment is a specialized very-low-fat diet. Even adhering to the diet, some patients may experience high triglycerides and pancreatitis. There currently are no comprehensive dietary guidelines. OBJECTIVE: To report best practices and develop comprehensive dietary guidelines for nutrition therapy in patients with FCS...

BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare genetic disorder characterized by a deficiency of lipoprotein lipase leading to extreme hypertriglyceridemia. Patients' burden of illness and quality of life have been poorly addressed in the literature. OBJECTIVE: To understand the ways in which FCS impacts patients' lives. METHODS: Investigation of Findings and Observations Captured in Burden of Illness Survey (IN-FOCUS) was a global web-based survey open to patients with FCS...

BACKGROUND: Familial chylomicronemia syndrome (FCS) is an ultra-rare phenotype that is usually caused by biallelic mutations in the LPL gene encoding lipoprotein lipase, or less often in APOC2, APOA5, LMF1, or GPIHBP1 genes encoding cofactors or interacting proteins. OBJECTIVES: We evaluated baseline phenotypes among FCS participants in a phase 3 randomized placebo-controlled trial of volanesorsen (NCT02211209). METHODS: Baseline clinical, fasting, and postfat load metabolic markers were assessed...

Plasma triglyceride concentrations are normally below 150 mg/dL in the fasting state. However, these lipids can reach values of several thousand mg/dL. Elevations in this range are due to a massive retention of chylomicrons and usually result from multiple genetic variants with superimposed influences such as diabetes and immune disorders. Less commonly, major gene defects in lipoprotein metabolism can be the cause. These may present soon after birth with strong evidence of familial penetrance. The causes of this syndrome have been discussed in a Roundtable published in the most recent issue of this Journal...

BACKGROUND: Extreme hypertriglyceridemia (eHTG; serum triglycerides ≥ 2000 mg/dL) poses a significant risk for acute pancreatitis. There is paucity of data regarding the prevalence and etiology of eHTG in children. OBJECTIVE: To determine the prevalence, clinical features and etiologies of patients with eHTG at a tertiary children's hospital in the United States and in the United States National Health and Nutrition Examination Survey (NHANES). METHODS: A retrospective analysis was conducted of the electronic medical records of the Children's Medical Center, Dallas, from 2000-2015, and the NHANES data from 2005-2014 for eHTG...

No abstract text is available yet for this article.

Familial chylomicronemia syndrome is characterized by severe elevation in serum triglycerides and an increased risk of acute pancreatitis. Although familial chylomicronemia syndrome is mainly caused by mutations in the lipoprotein lipase (LPL) gene, few causal mutations in other genes (ie, APOC2, APOA5, LMF1, and GPIHBP1) have also been reported. In this case report, we present the discovery of a novel mutation in the glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) gene and discuss its pathogenicity through a familial segregation study...

No abstract text is available yet for this article.

BACKGROUND AND AIMS: Type I hyperlipoproteinemia, also known as familial chylomicronemia syndrome (FCS), is a rare autosomal recessive disorder caused by variants in LPL, APOC2, APOA5, LMF1 or GPIHBP1 genes. The aim of this study was to identify novel variants in the LPL gene causing lipoprotein lipase deficiency and to understand the molecular mechanisms. METHODS AND RESULTS: A total of 3 individuals with severe hypertriglyceridemia and recurrent pancreatitis were selected from the Lipid Clinic at Sahlgrenska University Hospital and LPL was sequenced...

No abstract text is available yet for this article.

The examples from the history, as well as the recent view, clearly demonstrate a great change in the perception of hyperlipoprotienemias and dyslipidemias (HLP and DLP) at the end of 20th and at the beginning of 21st century. Our aim is not a complex overview about HLP and DLP. We just want to describe the changing position and importance of these diseases in clinical medicine. We will touch cardiology, angiology, but also diabetology, hepatology and gastroenterology (pancreas). HLP and DLP, which started as a research topic in laboratory became clinically interesting as risk factors of atherosclerosis...

Familial chylomicronemia syndrome (FCS) is a rare genetic disorder that is associated with severe hypertriglyceridemia and complications that often include recurrent pancreatitis beginning in childhood. Patients with FCS frequently struggle to maintain normality in their lives as a consequence of the necessity to severely restrict their intake of dietary fat coupled with the constant threat of recurrent pancreatitis. Patients typically face a high level of psychological stress and anxiety in association with reduced measures of quality of life...

BACKGROUND AND AIMS: Familial chylomicronemia syndrome is a rare autosomal recessive disorder leading to severe hypertriglyceridemia (HTG) due to mutations in lipoprotein lipase (LPL)-associated genes. Few data exist on the clinical features of the disorder or on comprehensive genetic approaches to uncover the causative genes and mutations. METHODS: Eight patients diagnosed with familial hyperchylomicronemia with recessive inheritance were included in this study (two males and six females; median age of onset 23...

PURPOSE OF REVIEW: Apolipoprotein CIII (ApoCIII) is now recognized as a key regulator in severe hypertriglyceridemia, chylomicronemia, and conditions of triglyceride-rich lipoprotein (TRL) remnant excess due to its inhibition of lipoprotein lipase (LPL) and hepatic lipase, leading to decreased hepatic reuptake of TRLs, as well as enhanced synthesis and secretion of VLDL from the liver. ApoCIII gain-of-function mutations are associated with atherosclerosis and coronary heart disease (CHD), and contribute to the development of cardiometabolic syndrome, hypertriglyceridemia, and type 2 diabetes mellitus...

PURPOSE OF REVIEW: This article reviews current knowledge concerning diabetic dyslipidemia and cardiovascular disease (CVD). It reviews strategies to reduce diabetes-associated CVD, including reducing low-density lipoprotein levels, lowering triglycerides, and increasing high-density lipoproteins (HDL). Special considerations, such as the multifactorial chylomicronemia syndrome and partial lipodystrophy, and the role of glucose-lowering strategies in the management of diabetic dyslipidemia are discussed...

BACKGROUND: The incidental finding of severe hypertriglyceridemia (HyperTG) in a child may suggest the diagnosis of familial chylomicronemia syndrome (FCS), a recessive disorder of the intravascular hydrolysis of triglyceride (TG)-rich lipoproteins. FCS may be due to pathogenic variants in lipoprotein lipase (LPL), as well as in other proteins, such as apolipoprotein C-II and apolipoprotein A-V (activators of LPL), GPIHBP1 (the molecular platform required for LPL activity on endothelial surface) and LMF1 (a factor required for intracellular formation of active LPL)...