Monogenic Familial Chylomicronemia Syndrome in Children: Clinical Divergences and Management Paradigms

Monogenic familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder caused by disrupted intravascular lipoprotein lipase (LPL) pathways. Phenotypic variation often leads to diagnostic delays. We contrast two unique pediatric presentations of FCS, highlighting distinct pathophysiology. Case 1 describes a 21-month-old girl with eruptive xanthomas, which was initially misdiagnosed as an infectious rash, later revealed to be secondary to severe hypertriglyceridemia of 100.6 mmol/L (reference range < 0.8 mmol/L). Molecular testing confirmed a genetic mutation in the GPIHBP1 gene. Case 2 describes a 2-day-old neonate with incidental finding of lipemia during jaundice evaluation, subsequently revealing a fasting triglyceride level of 8.5 mmol/L. Genetic analysis identified compound heterozygous mutations in the LPL gene. Case 1 required intensive insulin therapy, strict dietary fat restriction and adjunctive gemfibrozil. Case 2 was managed via dietary restriction and medium-chain triglyceride formula supplementation. This two-case series illustrates the diagnostic challenges of FCS in pediatric practice and the contribution of molecular confirmation to establishing the underlying aetiology and informing counselling and long-term management.