Clinical and Biochemical Features of Different Molecular Etiologies of Familial Chylomicronemia

Hegele, Robert A.; Ban, Matt; Wang, Jian; Digenio, Andrés; Alexander, Veronica J.; Arca, Marcello; Jones, Alan G.; Bruckert, Éric; Stroes, ES; Bergeron, Jean; Civeira, Fernando; Witztum, Joseph L.; Gaudet, Daniel

doi:10.1016/j.jacl.2017.04.098

Cited by 2 publications

(3 citation statements)

References 7 publications

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“…Amongst 14 individuals who consented to genetic testing, we found similar complex genetic influences as we observed previously in other severe HTG cohorts : 0/14 had bi‐allelic large‐effect mutations in LPL or related genes whilst 2/14 had heterozygous mutations in these genes ( APOA5 p.G185C and LPL p.G300R) and 7/14 had a polygenic risk score (PRS) for HTG in the top 80th percentile or higher. A high PRS for HTG is the most common genetic profile seen in adults with TG >10 mmol L −1 .…”

Section: Resultssupporting

confidence: 80%

Conservative management in hypertriglyceridemia‐associated pancreatitis

et al. 2019

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Background Severe hypertriglyceridemia (serum triglyceride >10 mmol L−1) is implicated in ~9% of acute pancreatitis cases. Certain guidelines list severe hypertriglyceridemia as an indication for plasmapheresis. Objective We assembled the natural trajectory of triglyceride levels in patients with acute pancreatitis due to severe hypertriglyceridemia who were managed conservatively without plasmapheresis to evaluate the effectiveness of this approach. Methods A retrospective chart review was performed on 22 hospital admissions for acute pancreatitis episodes considered to be caused by severe hypertriglyceridemia. Patients were managed supportively, with cessation of oral intake (NPO) and intravenous hydration. Insulin infusion was used in 12 patients to manage concurrent hyperglycaemia. Results Triglyceride levels for the group were evaluated using a mixed‐effects model. The average triglyceride level fell from 45.4 mmol L−1 on presentation to 13.3 mmol L−1 within 48 h, corresponding to a mean 69.8% decrease. Regression analysis showed a triglyceride half‐life of 30.6 h. Findings were similar for NPO‐only and insulin infusion subgroups. Conclusion Patients with severe hypertriglyceridemia and acute pancreatitis can be conservatively managed safely and effectively without plasmapheresis.

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Section: Resultssupporting

confidence: 80%

Conservative management in hypertriglyceridemia‐associated pancreatitis

et al. 2019

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“…Relatively few families worldwide with bi‐allelic mutations in these minor genes have been reported to date . Genetically defined LPL‐FCS and non‐LPL‐FCS patients were recently shown to have very similar baseline untreated clinical and biochemical phenotypes .…”

Section: Evidence Used In This Reviewmentioning

confidence: 99%

“…A marked reduction or absence of LPL activity (i.e. ≤20% of normal) was often used in the past to document LPL deficiency . However, this assay is no longer commonly available in clinical setting and is relatively unreliable, as the performance varies widely depending on the experience of the diagnostic laboratory.…”

Section: Evidence Used In This Reviewmentioning

confidence: 99%

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

et al. 2020

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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.

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Clinical and Biochemical Features of Different Molecular Etiologies of Familial Chylomicronemia

Cited by 2 publications

References 7 publications

Conservative management in hypertriglyceridemia‐associated pancreatitis

Conservative management in hypertriglyceridemia‐associated pancreatitis

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

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