Familial chylomicronemia syndrome. A sixty year follow-up in two siblings and their kindreds. Nosological and clinical considerations


      • Four subjects with familial chylomicronemia syndrome were identified.
      • Sixty-year clinical/biochemical follow-up was performed in 2 affected patients.
      • Genetic analysis disclosed a single LPL gene defect (c.984 G>T) in homozygosity.
      • Cardiovascular disease/pancreatitis prevalence and long-term survival are discussed.


      Familial chylomicronemia syndrome (FCS) is a rare and severe genetic disorder, characterized by marked elevation of plasma triglycerides, often diagnosed in infancy. We describe the long-term follow-up (almost 60 years), the diagnostic assessment and the management of two siblings with severe hypertriglyceridemia and a history of pancreatitis who also developed cardiovascular complications later in life. We recently disclosed that the surviving index case was homozygous for a pathogenic LPL gene variant (c.984 G>T, p.M328I). The same variant was also found in two apparently unrelated siblings with FCS living in the same geographical area as the index case.

      Graphical abstract


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        • Brunzell JD
        • Deeb SS.
        • et al.
        Familial lipoprotein lipase deficiency, apo C-II deficiency, and hepatic lipase deficiency.
        in: Scriver CR The Metabolic & Molecular Bases of Inherited Disease. Mc Graw Hill, New York2001: 2789-2816
        • Chyzhyk V
        • Brown AS.
        Familial chylomicronemia syndrome: a rare but devastating autosomal recessive disorder characterized by refractory hypertriglyceridemia and recurrent pancreatitis.
        Trends Cardiovasc Med. 2020; 30: 80-85
        • Dron JS
        • Hegele RA.
        Genetics of hypertriglyceridemia.
        Front Endocrinol. 2020; 11: 455
        • Davidson M
        • Stevenson M
        • Hsieh A
        • Ahmad Z
        • Roeters van Lennep J
        • et al.
        The burden of familial chylomicronemia syndrome: Results from the global IN-FOCUS study.
        J Clin Lipidol. 2018; 12: 898-907
        • Fellin R
        • Baggio G
        • Poli A
        • Augustin J
        • Baiocchi MR
        • Baldo G
        • et al.
        Familial lipoprotein lipase and apolipoprotein C-II deficiency. Lipoprotein and apoprotein analysis, adipose tissue and hepatic lipoprotein lipase levels in seven patients and their first degree relatives.
        Atherosclerosis. 1983; 49: 55-68
        • Manzato E
        • Zambon S
        • Marin R
        • Baggio G
        • Crepaldi G.
        Modifications of plasma lipoproteins after lipase activation in patients with chylomicronemia.
        J Lipid Res. 1986; 27: 1248-1258
        • Greten H
        • De Grella R
        • Klose G
        • Rascher W
        • De Gennes JL
        • Gjone E.
        Measurement of two plasma triglyceride lipases by an immunochemical method. Studies in patients with hypertriglyceridemia.
        J Lipid Res. 1976; 14: 203-210
        • Rabacchi C
        • Pisciotta L
        • Cefalù AB
        • Noto D
        • Fresa R
        • Tarugi P
        • et al.
        Spectrum of mutations of the LPL gene identified in Italy in patients with severe hypertriglyceridemia.
        Atherosclerosis. 2015; 241: 79-86
        • Mailly F
        • Palmen J
        • Muller DPR
        • Gibbs T
        • Lloyd J
        • Brunzell J
        • et al.
        Familial lipoprotein lipase (LPL) deficiency: a catalogue of LPL gene mutations identified in 20 patients from the UK, Sweden and Italy.
        Human Mutat. 1997; 10: 465-473
        • Wood S
        • Schertzer M
        • Hayden M
        • Ma Y.
        Support for founder effect for two lipoprotein lipase (LPL) gene mutations in French Canadians by analysis of GT microsatellites flanking the LPL gene.
        Hum Genet. 1993; 91: 312-316
        • Vigna GB
        • Fellin R.
        Hyperchylomicronemia: a neglected disease?.
        Italian J Med. 2009; 3: 189-190
        • Warden BA
        • Minnier J
        • Duel PB
        • Fazio S
        • Shapiro MD.
        Chylomicronemia syndrome: Familial or not?.
        J Clin Lipidol. 2020; 14: 201-206
        • Brahm AJ
        • Hegele RA.
        Combined hyperlipidemia: familial but not (usually) monogenic.
        Curr Opin Lipidol. 2016; 27: 131-140
        • Valdivielso P
        • Ramirez-Bueno A
        • Ewald N.
        Current knowledge of hypertriglyceridemic pancreatitis.
        Eur J Intern Med. 2014; 25: 689-694
        • Sandhu S
        • Al-Sarraf A
        • Taraboanta C
        • Frohlich J
        • Francis GA.
        Incidence of pancreatitis, secondary causes, and treatment of patients referred to a specialty lipid clinic with severe hypertriglyceridemia: a retrospective cohort study.
        Lipids Health Dis. 2011; 10: 157
        • Xiao AY
        • Tan MLY
        • Wu LM
        • Asrani VM
        • Windsor JA
        • Yadav D
        • Petrov MS.
        Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies.
        Lancet Gastroenterol Hepatol. 2016; 1: 45-55
        • Marco-Benedí V
        • Lamiquiz-Moneo I
        • Álvarez-Sala LA
        • Civeira F.
        Disappearance of recurrent pancreatitis after splenectomy in familial chylomicronemia syndrome.
        Atherosclerosis. 2018; 275: 342-345
        • Benlian P
        • De Gennes JL
        • Foubert L
        • Zhang H
        • Gagnè SE
        • Hayden M.
        Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the Lipoprotein Lipase gene.
        New Engl J Med. 1996; 335: 848-854
        • Castillo-Núñez Y
        • Morales-Villegas E
        • Aguilar-Salinas CA.
        Triglyceride-rich lipoproteins: their role in atherosclerosis.
        Rev Invest Clin. 2022; 74: 61-70
        • Caddeo A
        • Mancina RM
        • Pirazzi C
        • Russo C
        • Sasidharan K
        • Sandstedt J
        • et al.
        Molecular analysis of three known and one novel LPL variants in patients with type I hyperlipoproteinemia.
        Nutr Metab Cardiovasc Dis. 2018; 28: 158-164