Development of a Clinical Diagnostic Score for Familial Chylomicronemia Syndrome (FCS)

IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Journal of clinical lipidology Pub Date : 2024-07-01 DOI:10.1016/j.jacl.2024.04.062
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Abstract

Study Funding

This study was sponsored by Ionis Pharmaceuticals.

Background/Synopsis

Familial chylomicronemia syndrome (FCS) is an ultrarare, inherited disorder caused by impaired lipolysis leading to pathological accumulation of chylomicrons with severe hypertriglyceridemia (HTG) and systemic manifestations, the most serious of which is acute pancreatitis. FCS is challenging to manage, with lifelong implications for patients and their care providers. Genetic testing is the standard to confirm diagnosis but is not always feasible. Clinical FCS can be defined as both classical (autosomal recessive monogenic) and functional (signs/symptoms and biochemical traits of classical FCS without the classical variants or indeterminate genetic results). In 2017, European clinicians (Moulin et al.) developed a “FCS score” to differentiate between FCS and multifactorial chylomicronemia syndrome (MCS), a more common condition with some overlapping features. However, the applicability of this scoring system to North American FCS patients is unclear.

Objective/Purpose

Develop a clinical diagnostic score for North American practice patterns based on signs/symptoms and biochemical traits of FCS, regardless of genetic testing results.

Methods

The panel (9 United States and 1 Canadian physician with experience treating patients with FCS; 1 adult patient with FCS) followed the RAND/UCLA modified Delphi process by reviewing evidence on the diagnosis of FCS and developing 248 clinical scenarios of patients with varying characteristics such as age, triglyceride (TG) levels, and clinical history. Before and after a virtual meeting, panelists rated whether patients described in scenarios were likely to have classical or functional FCS or neither. Median post-meeting ratings were used to conduct linear regression analyses to develop a Clinical FCS Score. We assessed the score's face validity by totaling the Clinical FCS Score for each scenario and are calculating its sensitivity and specificity in a registry of patients.

Results

The final FCS score included age, HTG onset, body mass index, history of abdominal pain/pancreatitis, presence of secondary factors contributing to HTG, TG levels, ratio of TG/total cholesterol, and apolipoprotein B level (Figure). Experts agreed that scores ≥60 could be considered “Clinical FCS.”

Conclusions

We developed the first North American Clinical FCS Score that used a combination of signs/symptoms and biochemical traits. This score may aid clinicians in diagnosing patients with FCS who might otherwise be undiagnosed or misdiagnosed.

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制定家族性乳糜微粒血症综合征(FCS)临床诊断评分标准
研究经费本研究由 Ionis 制药公司赞助。背景/简介家族性乳糜微粒血症综合征(FCS)是一种超罕见的遗传性疾病,由脂肪分解功能受损导致乳糜微粒病理性积聚,并伴有严重的高甘油三酯血症(HTG)和全身表现,其中最严重的是急性胰腺炎。FCS 的治疗极具挑战性,会对患者及其护理人员造成终生影响。基因检测是确诊的标准,但并非总是可行。临床 FCS 可定义为经典性(常染色体隐性单基因遗传)和功能性(经典性 FCS 的体征/症状和生化特征,但没有经典变异或不确定的遗传结果)。2017 年,欧洲临床医生(Moulin 等人)制定了 "FCS 评分",以区分 FCS 和多因素乳糜微粒血症综合征(MCS),后者是一种更常见的病症,具有一些重叠的特征。目标/目的根据 FCS 的体征/症状和生化特征,不论基因检测结果如何,为北美的临床实践模式制定临床诊断评分。方法该小组(9 名美国和 1 名加拿大医生,他们都有治疗 FCS 患者的经验;1 名成年 FCS 患者)遵循兰德大学/加州大学洛杉矶分校修改过的德尔菲流程,回顾了有关 FCS 诊断的证据,并为具有不同特征(如年龄、甘油三酯 (TG) 水平和临床病史)的患者制定了 248 种临床方案。在虚拟会议前后,专家组成员对情景中描述的患者是否可能患有典型或功能性 FCS 或两者皆无进行评分。会后评分的中位数被用来进行线性回归分析,以得出临床 FCS 评分。结果最终的 FCS 评分包括年龄、高血压发病时间、体重指数、腹痛/胰腺炎病史、是否存在导致高血压的继发因素、总胆固醇水平、总胆固醇/总胆固醇比率和脂蛋白 B 水平(图)。专家们一致认为,得分≥60 分可被视为 "临床 FCS"。"结论我们制定了首个北美临床 FCS 评分标准,该评分标准结合了体征/症状和生化特征。该评分可帮助临床医生诊断可能未被诊断或误诊的 FCS 患者。
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来源期刊
CiteScore
7.00
自引率
6.80%
发文量
209
审稿时长
49 days
期刊介绍: Because the scope of clinical lipidology is broad, the topics addressed by the Journal are equally diverse. Typical articles explore lipidology as it is practiced in the treatment setting, recent developments in pharmacological research, reports of treatment and trials, case studies, the impact of lifestyle modification, and similar academic material of interest to the practitioner. While preference is given to material of immediate practical concern, the science that underpins lipidology is forwarded by expert contributors so that evidence-based approaches to reducing cardiovascular and coronary heart disease can be made immediately available to our readers. Sections of the Journal will address pioneering studies and the clinicians who conduct them, case studies, ethical standards and conduct, professional guidance such as ATP and NCEP, editorial commentary, letters from readers, National Lipid Association (NLA) news and upcoming event information, as well as abstracts from the NLA annual scientific sessions and the scientific forums held by its chapters, when appropriate.
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