{"title":"Development of a Clinical Diagnostic Score for Familial Chylomicronemia Syndrome (FCS)","authors":"","doi":"10.1016/j.jacl.2024.04.062","DOIUrl":null,"url":null,"abstract":"<div><h3>Study Funding</h3><p>This study was sponsored by Ionis Pharmaceuticals.</p></div><div><h3>Background/Synopsis</h3><p>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.</p></div><div><h3>Objective/Purpose</h3><p>Develop a clinical diagnostic score for North American practice patterns based on signs/symptoms and biochemical traits of FCS, regardless of genetic testing results.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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.”</p></div><div><h3>Conclusions</h3><p>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<strong>.</strong></p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of clinical lipidology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1933287424001090","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
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.
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.