Familial Chylomicronemia Syndrome: Clinical and Molecular Data From a Portuguese Cohort

Familial Chylomicronemia Syndrome (FCS) is a rare autosomal recessive disorder caused by biallelic variants in LPL, APOC2, GPIHBP1, APOA5, or LMF1. These defects impair triglyceride-rich lipoprotein hydrolysis, leading to xanthomas, abdominal pain, hepatomegaly, lipemia retinalis, and recurrent pancreatitis. Multifactorial Chylomicronemia Syndrome (MCS) often results from monoallelic variants in these genes and/or a high polygenic risk score, presenting a similar phenotype; thus, genetic testing is required for accurate differentiation. This study aimed to clinically and genetically characterize 45 individuals with severe hypertriglyceridemia in Portugal. Lipid profile and molecular analysis of the five canonical genes were performed. Moulin’s score was applied in 17 cases. The mean pretreatment triglyceride level was 2570 mg/dL. Sixteen individuals had pancreatitis, four had hepatomegaly, and three both conditions. Ten cases carried biallelic variants: five in LPL (three identical, two compound heterozygous), one in APOC2, one frameshift in LMF1, one frameshift and one stop in APOA5, and one total exon 4 deletion in GPIHBP1 (all identical variants). All were classified as “very likely FCS” by Moulin’s score. Twenty-one individuals had heterozygous variants in LPL, APOA5, LMF1, and GPIHBP1 and were considered MCS; three of them also scored as “very likely FCS.” Ten patients had negative genetic studies (five scored as “unlikely FCS”), and four remain under investigation. Early recognition of FCS is crucial to prevent life-threatening complications. A confirmed molecular diagnosis enables precise distinction between FCS and MCS, improving management and prognosis. These findings underscore the importance of incorporating genetic testing into the diagnostic workup of severe hypertriglyceridemia in Portugal.

Palavras-chave

Familial Chylomicronemia Syndrome Familial chylomicronemia Dyslipidemia Triglycerides Doenças Cardio e Cérebro-vasculares

URI

http://hdl.handle.net/10400.18/11101

Coleções

DPSPDNT - Apresentações orais em reuniões nacionais

Licença CC

Sem licença CC

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