The Ongoing Utility of lipoprotein lipase activity in diagnosing familial Chylomicronemia Syndrome

TL;DR

This study shows that measuring lipoprotein lipase activity can help diagnose a rare genetic disorder called Familial Chylomicronemia Syndrome, especially when genetic tests are unclear.

Contribution

The study establishes a specific cut-off for lipoprotein lipase activity to differentiate between two types of chylomicronemia syndrome.

Findings

A LPL activity cut-off of 25% of the median of normotriglyceridemic controls effectively identifies FCS patients.

LPL activity aids diagnosis when genetic results are inconclusive.

Specialized lab support is crucial for accurate FCS diagnosis.

Abstract

Given that lipoprotein lipase (LPL) activity assays are not standardized for clinical use, we aimed to define reference values applicable to our clinical setting and identify a cut-off point to help distinguish Familial Chylomicronemia Syndrome from Multifactorial Chylomicronemia Syndrome, particularly in patients with inconclusive genetic findings.

We evaluated 28 patients with a history of TG levels above 880 mg/dL (10 mmol/L), and assessed their likelihood of FCS using the Moulin score. LPL activity was measured in post-heparin plasma using a radiometric assay. Thirty normotriglyceridemic controls were used to define reference values. Genetic testing for FCS canonical genes and lipid profile was performed in all sHTG patients.

The reference value for LPL activity was 33.3 (18.7–70.3) mIU, with a cut-off of 8.42 mIU (25 % of the median of NTG) to distinguish FCS from MCS. Eighteen patients without genetic variants in canonical genes, a Moulin score <9 and LPL activity >25 % of NTG, were classified as MCS. Five genetic diagnosed FCS patients, with a Moulin score>10 presented LPL activity <25 % of NTG. Four patients with inconclusive genetic results and a Moulin score>10 were classified as FCS according to LPL activity.

LPL activity in patients with sHTG could be useful for differentiating FCS and MCS, particularly in patients with ambiguous or negative genetic findings, highlighting the need for specialized laboratory support in diagnostics.

•LPL activity helps distinguish FCS from multifactorial causes of sHTG.•LPL cut-off value of 25 % of the median of NTG identifies FCS patients with high accuracy.•LPL activity aids diagnosis when genetic results are inconclusive.•Specialized lab support is crucial for accurate FCS diagnosis.

LPL activity helps distinguish FCS from multifactorial causes of sHTG.

LPL cut-off value of 25 % of the median of NTG identifies FCS patients with high accuracy.

LPL activity aids diagnosis when genetic results are inconclusive.

Specialized lab support is crucial for accurate FCS diagnosis.

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