Advertisement

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

      Highlights

      • 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.

      Abstract

      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

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Clinical Lipidology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • 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