Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder caused by mutations in genes regulating lipoprotein lipase activity, typically manifesting early in life. We describe a 7 Show more
Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder caused by mutations in genes regulating lipoprotein lipase activity, typically manifesting early in life. We describe a 70-year-old man with severe refractory hypertriglyceridemia, chronic hyperCKemia, and protein-energy malnutrition, ultimately diagnosed with FCS due to a homozygous pathogenic LPL variant (c.844G>T; p.Glu282*). Despite long-standing disease and comorbidities, treatment with volanesorsen, an antisense oligonucleotide targeting apolipoprotein C-III mRNA, produced a 74% reduction in triglyceride levels and marked clinical improvement. This case underscores that FCS may remain undetected until late adulthood, particularly when confounded by diabetes or chronic kidney disease. Recognition of characteristic biochemical profiles and family history is essential to avoid diagnostic delay and prevent irreversible pancreatic damage and malnutrition. Even in elderly patients, targeted therapy can substantially improve metabolic control and quality of life. Show less
Familial Hypercholesterolemia (FH) is a common genetic disorder characterized by elevated LDL-cholesterol levels and an increased risk of premature cardiovascular disease. While pathogenic variants in
Familial hypercholesterolemia (FH) is a genetic disease, usually with onset during childhood, characterized by elevated blood LDL cholesterol levels and potentially associated with severe cardiovascul Show more
Familial hypercholesterolemia (FH) is a genetic disease, usually with onset during childhood, characterized by elevated blood LDL cholesterol levels and potentially associated with severe cardiovascular complications. Concerning mutated genes in FH, such as Show less
The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat Familial Chylomicronemia Syndrome (FCS). Cases of decreased platelet count are reported among patients tr Show more
The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat Familial Chylomicronemia Syndrome (FCS). Cases of decreased platelet count are reported among patients treated with volanesorsen. The aim of the study was to evaluate platelet function and thrombin generation (TG) assessment in FCS patients receiving volanesorsen. We performed a cross-sectional study on FCS patients treated with volanesorsen. Changes in platelet count PLC were assessed from baseline to Tw12 and Tw36. To assess TG, samples were processed by CAT (with PPP-reagent LOW). The results were expressed by the thrombogram graphic (thrombin variation over time); LagTime; endogenous thrombin potential (ETP); peak; time to reach peak (ttpeak), StartTail and Velocity Index. Platelet aggregation was assessed by testing different agonists using the turbidimetry method. Four FCS patients and four matched healthy controls were included in the present study. Changes in PLC were 30% at Tw12 and 34% at Tw36. Thrombin generation results showed values in the normal range (for patients and controls, respectively, LagTime:10.42 ± 4.40 and 9.25 ± 0.99; ttPeak:14.33 ± 4.01 and 13.10 ± 0.67; StartTail: 32.13 ± 3.54 and 29.46 ± 1.69; Velocity Index: 20.21 ± 3.63 and 33.05 ± 13.21; ETP: 599.80 ± 73.47 and 900.2 ± 210.99; peak value: 76.84 ± 1.07 and 123.30 ± 39.45) and no significant difference between cases and controls. Platelet aggregation test showed values in range, with no significant difference compared to healthy controls. Our study showed for the first time that no significant changes in general hemostasis assessed by TG and in platelet function were observed in FCS patients receiving volanesorsen. Show less
Patients with severe hypertriglyceridaemia (sHTG) are often refractory to lipid-lowering therapy. Apolipoprotein (Apo) CIII inhibition could be promising to treat subjects with sHTG. The antisense oli Show more
Patients with severe hypertriglyceridaemia (sHTG) are often refractory to lipid-lowering therapy. Apolipoprotein (Apo) CIII inhibition could be promising to treat subjects with sHTG. The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat sHTG. We performed a systematic review and meta-analysis of RCTs on the efficacy and safety of volanesorsen as compared to placebo treatment in patients with severe HTG. Studies were systematically searched in the PubMed, Web of Science and Scopus databases according to PRISMA guidelines. The last search was performed on 7 February 2022. Four studies showed significant reduction in TG after 3 months of treatment with volanesorsen as compared with placebo (MD: -73.9%; 95%CI: -93.5%, -54.2; p < .001 I In patients with severe HTG, volanesorsen is associated with a significant reduction in TG, VLDL-C, Apo-B48 and non-HDL-C and increment of HDL-C as compared to placebo. Documented efficacy is accompanied by an acceptable safety profile. Show less