Search Results (3)

Hypertriglyceridemia (HTG) is associated with a residual risk of atherosclerotic cardiovascular disease. Extremely elevated triglyceride (TG) concentrations, particularly due to familial chylomicronemia syndrome (FCS), pose a risk for acute pancreatitis. Standard therapies with statins, fibrates, omega-3 fatty acids, and niacin may be insufficient to reduce elevated TG levels and improve clinical outcomes in patients with HTG. Novel antisense oligonucleotides and small interfering ribonucleic acids target the key modulators of TG-rich lipoprotein catabolism. Among apolipoprotein C-III (apoC-III) inhibitors, olezarsen and plozasiran appear to be safer alternatives for volanesorsen regarding the risk of drug-induced thrombocytopenia in patients with FCS or severe HTG. After the failure of vupanorsen, a new angiopoietin-like protein 3 (ANGPTL3) inhibitor, zodasiran, demonstrated the potential to decrease TG levels in patients with moderate HTG. Meanwhile, the fibroblast growth factor 21 (FGF21) analog, pegozafermin, became another candidate for the treatment of severe HTG. This comprehensive review outlines pharmacological targets in TG-rich lipoprotein metabolism, discusses international guidelines, and summarizes the latest evidence from clinical trials to provide insight into the current and emerging treatment options for primary HTG. Full article

Primary hypertriglyceridemia (PHTG) is characterized by a high concentration of triglycerides (TG); it is divided between familial hyperchylomicronemia syndrome and multifactorial chylomicronemia syndrome. In Mexico, hypertriglyceridemia constitutes a health problem in which the genetic bases have been scarcely explored; therefore, our objective was to describe biochemical–clinical characteristics and variants in the APOA5, GPIHBP1, LMF1, and LPL genes in patients with primary hypertriglyceridemia. Thirty DNA fragments were analyzed using PCR and Sanger sequencing in 58 unrelated patients. The patients’ main clinical–biochemical features were hypoalphalipoproteinemia (77.6%), pancreatitis (18.1%), and a TG median value of 773.9 mg/dL. A total of 74 variants were found (10 in APOA5, 16 in GPIHBP1, 34 in LMF1, and 14 in LPL), of which 15 could be involved in the development of PHTG: 3 common variants with significative odds and 12 heterozygous rare pathogenic variants distributed in 12 patients. We report on the first Mexican patient with hyperchylomicronemia syndrome due to GPIHBP1 deficiency caused by three variants: p.R145*, p.A154_G155insK, and p.A154Rfs*152. Moreover, eleven patients were heterozygous for the rare variants described as causing PHTG and also presented common variants of risk, which could partially explain their phenotype. In terms of findings, two novel genetic variants, c.-40_-22del LMF1 and p.G242Dfs*10 LPL, were identified. Full article

(1) Background: Familial chylomicronemia syndrome (FCS) is a very rare autosomal recessive disorder characterized by severely elevated triglycerides and clinical symptoms in early childhood mainly presenting with abdominal pain, acute pancreatitis and hepatosplenomegaly. Primary treatment is a lifelong very strict low-fat diet, which might be challenging in pediatric patients. So far, data about children with FCS are rare. The aim of this study was to show the familial chylomicronemia syndrome traffic light table for pediatric patients and to assess the dietary fat intake and impact on triglycerides in children with FCS. (2) Methods: We performed a retrospective analysis in four children (50% male) affected by FCS from the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna between January 2002 and September 2020. (3) Results: The four patients presented with classical FCS symptoms and showed baseline triglycerides (TG) exceeding 30,000 mg/dL in two patients, 10,000 mg/dL and 2400 mg/dL in one patient each. After diagnosis, fat percentage of total daily caloric intake was decreased and resulted immediately in triglyceride reduction. In all patients, FCS was genetically confirmed by mutations in genes encoding lipoprotein lipase. Acute pancreatitis and hepatosplenomegaly disappeared under the fat-restricted diet. A FCS traffic light table was developed as a dietary tool for affected families. (4) Conclusions: A restriction of dietary fat between 10% to 26% of the total daily caloric intake was feasible and effective in the long-term treatment of genetically confirmed FCS in children and could reduce the risk for acute pancreatitis. The dietary tool, the pediatric FCS traffic light table and the age-appropriate portion sizes for patients between 1 to 18 years, supports children and their parents to achieve and adhere to the lifelong strict low-fat diet. Full article