A-250 Familial Chylomicronemia Syndrome: A Case Report Highlighting the Critical Role of Clinical Biochemistry Laboratories in Diagnosis

Background Familial chylomicronemia syndrome (FCS), a rare autosomal recessive disorder (1-3 per million), is characterized by severe hypertriglyceridemia (HTGs) due to impaired chylomicron catabolism, primarily linked to lipoprotein lipase (LPL) deficiency. Diagnosis remains challenging, as genetic testing fails to identify causal variants in ∼30% of cases, necessitating complementary biochemical approaches. Methods Ten HTGs patients (TG >880 mg/dL) underwent LPL activity measurement using a standardized post-heparin plasma assay. Biochemical parameters (total cholesterol, TG, ApoB) were analyzed on a Mindray BS360E autoanalyzer (intra-assay CV =1.5%). LPL activity was quantified via [³H]-triolein hydrolysis, with reference values established from 22 normotriglyceridemic controls. Genetic testing (Illumina NovaSeq) targeted five canonical FCS genes. Moulin scores were calculated for clinical stratification. Results Reference LPL activity (median: 33.3 mIU/mL) showed no cofactor dependency in controls. Three FCS-confirmed cases exhibited LPL activity <20% of controls (0.0-5.2 mIU/mL), correlating with homozygous/double heterozygous mutations in APOA5 or LPL. Two patients with APOC2/APOE variants showed partial LPL restoration (+49-63% activity) upon cofactor addition. Moulin scores =10 showed 57% sensitivity for FCS, while 3/7 high-score patients had non-FCS genotypes (APOE). Mindray-based TG/ApoB ratios varied significantly between FCS (2.06-5.68) and non-FCS cases (7.43-30.45). Conclusion LPL activity measurement using standardized Mindray platforms enhances FCS diagnosis, particularly in genetically ambiguous cases. A 20% LPL activity threshold reliably differentiates FCS from multifactorial chylomicronemia. Clinical biochemistry laboratories play pivotal roles in validating functional assays and bridging genetic diagnostic gaps, enabling targeted therapies to reduce pancreatitis risk.