Chylomicronemia: Differences between familial chylomicronemia syndrome and multifactorial chylomicronemia

Paquette, Martine; Bernard, Sophie; Hegele, Robert A.; Baass, Alexis

doi:10.1016/j.atherosclerosis.2018.12.019

Cited by 77 publications

(111 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The differences in the time course change of triglyceride levels were paralleled with an increased risk of complications, namely AP, which was found to be higher in FCS than in MCS. Also Paquette et al 40 have recently reported in a cross-sectional analysis that FCS patients have higher frequency of AP than MCS. However, because of the longitudinal nature of our study, we have been able to expand these findings estimating that FCS showed a 3-fold increased risk of incident AP events in comparison with MCS patients.…”

Section: Translational Sciences -Almentioning

confidence: 91%

Spectrum of Mutations and Long-Term Clinical Outcomes in Genetic Chylomicronemia Syndromes

D’Erasmo

Costanzo

Cassandra

et al. 2019

ATVB

View full text Add to dashboard Cite

OBJECTIVE: Familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS) are the prototypes of monogenic and polygenic conditions underlying genetically based severe hypertriglyceridemia. These conditions have been only partially investigated so that a systematic comparison of their characteristics remains incomplete. We aim to compare genetic profiles and clinical outcomes in FCS and MCS. APPROACH AND RESULTS:Thirty-two patients with severe hypertriglyceridemia (triglyceride >1000 mg/dL despite lipid-lowering treatments with or without history of acute pancreatitis) were enrolled. Rare and common variants were screened using a panel of 18 triglyceride-raising genes, including the canonical LPL, APOC2, APOA5, GP1HBP1, and LMF1. Clinical information was collected retrospectively for a median period of 44 months. Across the study population, 37.5% were classified as FCS due to the presence of biallelic, rare mutations and 59.4% as MCS due to homozygosity for nonpathogenic or heterozygosity for pathogenic variants in canonical genes, as well as for rare and low frequency variants in noncanonical genes. As compared with MCS, FCS patients showed a lower age of hypertriglyceridemia onset, higher levels of on-treatment triglycerides, and 3-fold higher incidence rate of acute pancreatitis. CONCLUSIONS:Our data indicate that the genetic architecture and natural history of FCS and MCS are different. FCS expressed the most severe clinical phenotype as determined by resistance to triglyceride-lowering medications and higher incidence of acute pancreatitis episodes. The most common genetic abnormality underlying FCS was represented by biallelic mutations in LPL while APOA5 variants, in combination with high rare polygenic burden, were the most frequent genotype of MCS. VISUAL OVERVIEW:An online visual overview is available for this article.

show abstract

Section: Translational Sciences -Almentioning

confidence: 91%

Spectrum of Mutations and Long-Term Clinical Outcomes in Genetic Chylomicronemia Syndromes

D’Erasmo

Costanzo

Cassandra

et al. 2019

ATVB

View full text Add to dashboard Cite

show abstract

“…Whilst occasional instances of ASCVD have been reported in FCS patients [22,23], these are considered exceptions that prove the rule. In contrast, other forms of severe HTG, such as multifactorial chylomicronemia or dysbetalipoproteinemia, appear to be associated with ASCVD [4,6,24].…”

Section: What Is the Clinical Presentation Of Fcs?mentioning

confidence: 93%

“…Indeed, a higher prevalence of metabolic abnormalities (elevated body mass index, high fasting glucose or high blood pressure) and ASCVD (prevalence of 17% in MCM vs 0% in FCS) were observed in the MCM group, whereas the FCS group had higher frequency of pancreatitis (prevalence of 60% in FCS vs 6% in MCM), multiple pancreatitis (prevalence of 48% in FCS vs 3% in MCM) and abdominal pain [6]. However, the mean triglycerides levels were similar between groups [6]. Whilst lifetime risk of pancreatitis is lower in MCM compared to FCS, the higher prevalence of MCM means that it underlies most cases of HTG-associated pancreatitis.…”

Section: Comparison With Other Causes Of Hypertriglyceridaemiamentioning

confidence: 96%

Familial chylomicronemia syndrome: an under‐recognized cause of severe hypertriglyceridaemia

et al. 2020

View full text Add to dashboard Cite

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder of chylomicron metabolism causing severe elevation of triglyceride (TG) levels (>10 mmol L−1). This condition is associated with a significant risk of recurrent acute pancreatitis (AP). AP caused by hypertriglyceridaemia (HTG) has been associated with a worse prognosis and higher mortality rates compared to pancreatitis of other aetiology. Despite its association with poor quality of life and increased lifelong risk of HTG‐AP, few healthcare providers are familiar with FCS. Because this condition is under‐recognized, the majority of FCS patients are diagnosed after age 20 often after consulting several physicians. Although other forms of severe HTG such as multifactorial chylomicronemia have been associated with high atherosclerotic cardiovascular disease (ASCVD) risk and metabolic abnormalities, ASCVD and metabolic syndrome are not usually observed in FCS patients. Because FCS is a genetic condition, the optimal diagnosis strategy remains genetic testing. The presence of bi‐allelic pathogenic mutations in LPL, APOC2, GPIHBP1, APOA5 or LMF1 genes confirms the diagnosis. However, some cases of FCS caused by autoantibodies against LPL or GPIHBP1 proteins have also been reported. Furthermore, a clinical score for the diagnosis of FCS has been proposed but needs further validation. Available treatment options to lower triglycerides such as fibrates or omega‐3 fatty acids are not efficacious in FCS patients. Currently, the cornerstone of treatment remains a lifelong very low‐fat diet, which prevents the formation of chylomicrons. Finally, inhibitors of apo C‐III and ANGPTL3 are in development and may eventually constitute additional treatment options for FCS patients.

show abstract

“…While the relative risk is higher in monogenic chylomicronaemia, in absolute terms hyper-triglyceridaemia-induced pancreatitis is seen much more frequently with multifactorial or polygenic chylo-micronaemia. 48 Whatever the genetic basis, the severity of hypertriglyceridaemia (and thus propensity to develop pancreatitis) is increased by consumption of highfat foods, alcohol, oestrogen-containing medications, pregnancy, obesity and insulin resistance, diabetes, hypothyroidism, or medications that increase VLDL secretion (eg, steroids). 38 Because both parents will be obligate heterozygotes for any of these genes, screening of siblings of an affected child is obligatory; a quarter of siblings will also have biallelic or homozygous mutations.…”

Section: Clinical Presentationmentioning

confidence: 99%

“…39 The absence of secondary factors, and diagnosis at a very early age, are suggestive of monogenic chylomicronaemia, particularly if hypertriglyceridaemia is associated with pancreatitis. 48 Low plasma concentrations of plasma apolipoprotein B (<0·75 g/L) might help differentiate patients with monogenic versus multifactorial chylomicronaemia. 48 A history of severe hypertri glyceridaemia in a sibling also suggests a strong genetic basis for this disorder.…”

Section: Reviewmentioning

confidence: 99%

Rare dyslipidaemias, from phenotype to genotype to management: a European Atherosclerosis Society task force consensus statement

Hegele

Borén

Ginsberg

et al. 2020

The Lancet Diabetes & Endocrinology

137

101

View full text Add to dashboard Cite

Genome sequencing and gene-based therapies appear poised to advance the management of rare lipoprotein disorders and associated dyslipidaemias. However, in practice, underdiagnosis and undertreatment of these disorders are common, in large part due to interindividual variability in the genetic causes and phenotypic presentation of these conditions. To address these challenges, the European Atherosclerosis Society formed a task force to provide practical clinical guidance focusing on patients with extreme concentrations (either low or high) of plasma low-density lipoprotein cholesterol, triglycerides, or high-density lipoprotein cholesterol. The task force also recognises the scarcity of quality information regarding the prevalence and outcomes of these conditions. Collaborative registries are needed to improve health policy for the care of patients with rare dyslipidaemias.

show abstract

Chylomicronemia: Differences between familial chylomicronemia syndrome and multifactorial chylomicronemia

Cited by 77 publications

References 13 publications

Spectrum of Mutations and Long-Term Clinical Outcomes in Genetic Chylomicronemia Syndromes

Spectrum of Mutations and Long-Term Clinical Outcomes in Genetic Chylomicronemia Syndromes

Familial chylomicronemia syndrome: an under‐recognized cause of severe hypertriglyceridaemia

Rare dyslipidaemias, from phenotype to genotype to management: a European Atherosclerosis Society task force consensus statement

Contact Info

Product

Resources

About