Key Differences Between Familial and Multifactorial Chylomicronemia Syndromes Identified

A recent study analyzing clinical and biochemical characteristics in patients with severe hypertriglyceridemia found distinct phenotypic differences between familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS). Patients with FCS were significantly younger at diagnosis and symptom onset, had a lower body mass index (BMI), and experienced pancreatitis more frequently than those with MCS. These findings highlight key distinctions between the two conditions, which may help refine diagnostic and treatment approaches.

FCS and MCS both present with severe hypertriglyceridemia, defined as plasma triglyceride levels of at least 10 mmol/L (≥885 mg/dL). However, clinical differentiation between these syndromes can be challenging, and misclassification may impact patient management. This study aimed to clarify distinguishing features by evaluating clinical and biochemical profiles of genetically confirmed FCS and MCS cases.

Researchers performed targeted genetic sequencing on 193 patients with severe hypertriglyceridemia, classifying them into FCS or MCS groups. They then compared demographic, clinical, and biochemical characteristics to identify differentiating factors between the two conditions.

Patients with FCS were younger than those with MCS (31.4 ± 16.7 vs. 51.0 ± 11.3 years; P = .003) and had an earlier age at symptom onset (15.0 ± 15.8 vs. 37.8 ± 8.8 years; P = .00066). Patients with FCS also had a significantly lower BMI (23.3 ± 3.1 vs. 30.7 ± 5.0 kg/m²; P = .000016) and were more likely to have experienced pancreatitis (81.8% vs. 35.2%; P = .003) compared with those with MCS. Biochemical differences included a higher triglyceride-to-total cholesterol ratio in FCS compared with MCS (4.18 ± 0.92 vs. 1.08 ± 0.51; P < .0001) and lower plasma apolipoprotein B levels (0.56 ± 0.15 vs. 1.02 ± 0.43 g/L; P < .0001). Among patients with MCS, those with heterozygous pathogenic variants had more severe clinical presentations than other MCS subgroups.

“While genetic analysis of patients with persistent severe hypertriglyceridemia can definitively diagnose FCS, 8.2% of MCS patients with sustained refractory hypertriglyceridemia behave functionally as if they have FCS, which should influence their eligibility for novel therapies for severe hypertriglyceridemia,” the study authors concluded.

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:dgae613. doi:10.1210/clinem/dgae613