
Targeted DNA sequencing in 193 patients with severe hypertriglyceridemia has shone new light on differences and similarities between familial chylomicronaemia syndrome (FCS) and multifactorial chylomicronaemia syndrome (MCS).
The study showed that patients with FCS were significantly younger than those with MCS (31.4±16.7 vs. 51.0±11.3 years; p=0.003), with earlier age at symptom onset (15.0±15.8 vs. 37.8±8.8 years; p=0.00066), lower body mass index (23.3±3.1 vs. 30.7±5.0 kg/m2; p=0.000016), and higher prevalence of pancreatitis events (81.8% vs. 35.2%; p=0.003). Those with FCS also had a higher ratio of TG to total cholesterol than those with MCS (4.18±0.92 vs 1.08±0.51, p<0.0001) and lower plasma apolipoprotein B ( 0.56±0.15 vs 1.02±0.43 g/L, p<0.0001).
Patients with MCS with heterozygous pathogenic variants had a relatively more severe clinical presentation than those in other MCS genetic sub-groups.
Professor Rob Hegele (pictured, above), Robarts Research Institute, Ontario, Canada, and colleagues concluded that patients with FCS have notable phenotypic differences compared to those with MCS, although there is overlap. They pointed out that, while genetic analysis of patients with persistent severe hypertriglyceridemia can definitively diagnose FCS, 8.2% of those with MCS with sustained refractory hypertriglyceridemia behave functionally as if they have FCS. This is something that should influence their eligibility for novel therapies for severe hypertriglyceridemia, added the researchers.
Reference
- Spagnuolo CM, Wang J, McIntyre AD, Kennedy BA, Hegele RA. Comparison of patients with familial chylomicronemia syndrome and multifactorial chylomicronemia syndrome. J Clin Endocrinol Metab. 2024 Sep 6:dgae613. doi: 10.1210/clinem/dgae613. Epub ahead of print. PMID: 39238074.