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

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.