Spagnuolo Catherine M, Wang Jian, McIntyre Adam D, Kennedy Brooke A, Hegele Robert A
Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada, N6A 5B7.
Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada, N6A 5B7.
J Clin Endocrinol Metab. 2025 Mar 17;110(4):1158-1165. doi: 10.1210/clinem/dgae613.
Patients with rare familial chylomicronemia syndrome (FCS) and relatively common multifactorial chylomicronemia syndrome (MCS) both express severe hypertriglyceridemia, defined as plasma triglyceride concentration ≥10 mmol/L (≥885 mg/dL). Clinically there can be confusion between the 2 conditions.
To compare clinical and biochemical phenotypes in patients with genotypically characterized FCS and MCS.
We performed targeted sequencing of DNA from 193 patients with severe hypertriglyceridemia, classified them as having either FCS or MCS, and compared clinical and biochemical characteristics.
Patients with FCS were significantly younger than patients with MCS (31.4 ± 16.7 vs 51.0 ± 11.3 years; P = .003), with earlier age at symptom onset (15.0 ± 15.8 vs 37.8 ± 8.8 years; P = .00066), lower body mass index (23.3 ± 3.1 vs 30.7 ± 5.0 kg/m2; P = .000016), and higher prevalence of pancreatitis events (81.8% vs 35.2%; P = .003). Furthermore, patients with FCS had a higher ratio of triglyceride to total cholesterol (ie, 4.18 ± 0.92 vs 1.08 ± 0.51; P < .0001) and lower plasma apolipoprotein B (ie, 0.56 ± 0.15 vs 1.02 ± 0.43 g/L; P < .0001) than patients with MCS. Patients with MCS with heterozygous pathogenic variants had a relatively more severe clinical presentation than other MCS genetic subgroups.
Patients with FCS have notable phenotypic differences from patients with MCS, although there is overlap. While genetic analysis of patients with persistent severe hypertriglyceridemia can definitively diagnose FCS, 8.8% of patients with MCS with sustained refractory hypertriglyceridemia behave functionally as if they have FCS, which should influence their eligibility for novel therapies for severe hypertriglyceridemia.
患有罕见的家族性乳糜微粒血症综合征（FCS）和相对常见的多因素乳糜微粒血症综合征（MCS）的患者均表现出严重的高甘油三酯血症，定义为血浆甘油三酯浓度≥10 mmol/L（≥885 mg/dL）。临床上这两种情况可能会混淆。
比较基因分型明确的FCS和MCS患者的临床和生化表型。
我们对193例严重高甘油三酯血症患者的DNA进行了靶向测序，将他们分类为患有FCS或MCS，并比较了临床和生化特征。
FCS患者比MCS患者明显年轻（31.4±16.7岁对51.0±11.3岁；P = 0.003），症状出现的年龄更早（15.0±15.8岁对37.8±8.8岁；P = 0.00066），体重指数更低（23.3±3.1对30.7±5.0 kg/m2；P = 0.000016），胰腺炎事件的发生率更高（81.8%对35.2%；P = 0.003）。此外，FCS患者的甘油三酯与总胆固醇的比值更高（即4.18±0.92对1.08±0.51；P < 0.0001），血浆载脂蛋白B更低（即0.56±0.15对1.02±0.43 g/L；P < 0.0001）。具有杂合致病变异的MCS患者的临床表现比其他MCS基因亚组相对更严重。
FCS患者与MCS患者有显著的表型差异，尽管存在重叠。虽然对持续性严重高甘油三酯血症患者进行基因分析可以明确诊断FCS，但8.8%的持续性难治性高甘油三酯血症MCS患者在功能上表现得好像患有FCS，这应该会影响他们接受严重高甘油三酯血症新疗法的资格。
