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EnglishFamilial chylomicronemia syndrome (FCS) is caused by homozygous or compound heterozygous mutations in the lipoprotein lipase gene (LPL) or its cofactors. Historically, the syndrome has been considered non-atherogenic for the low levels of low-density lipoprotein cholesterol (LDL-C), even though premature atherosclerosis has been hypothesized in FCS subjects as a consequence of a defective lipolysis [1]. In this issue of Atherosclerosis, Teramoto and collaborators clinically characterized eight unrelated patients affected by FCS and performed a targeted next-generation sequencing on a panel of 4813 genes associated with the phenotypes of interest. All subjects exhibited lactescent or cream-layer serum and three of them had a history of recurrent acute pancreatitis. Teramoto et al. identified four pathogenic (or likely pathogenic) mutations in the LPL gene (including one novel mutation and a variant of uncertain significance) and suggested that atherosclerotic disease may not be accelerated by hyperchylomicronemia [2]. Atherosclerotic lesions are not considered in the diagnostic algorithm for FCS, lately proposed by Stroes et al. [3], even though loss-of-function variants in the angiopoietin-like 3 (ANGPTL3) gene (secondly resulting in the inhibition of LPL activity) have been recently associated with a lower incidence of cardiovascular disease [4]. Certainly this study's sample size is commensurate with the rarity of the disease, though it is way too small to allow us to make statistically significant inferences going beyond some justified clinical suggestions. Hence the importance to increase the current knowledge about FCS of a global, multicenter and prospective observational registry, following for a long period of time the natural course of the disease and clinical outcomes of affected individuals [5]. Nowadays, FCS has an estimated prevalence in the population of 1:1.000.000 [6], with well-recognized major effects on both physical and mental health. The consistently high triglycerides levels can result in clinically relevant manifestations including severe abdominal pain and acute pancreatitis, being potentially fatal or leading to pancreatic damage and permanent exocrine or endocrine insufficiency [7]. The IN-FOCUS study, examining the impact of chylomicronemia on FCS patients' lives, has highlighted another aspect of the disease. FCS has a major impact on quality of life, also significantly influencing career choice and employment status of the patients, as a result of the chances of having a pain attack anytime [7]. LPL deficiency (LPL-D) patients show a bland or even absent response to the traditional lipid-lowering drugs, such as fibrates and omega-3 acid ethyl esters. At the same time, plasmapheresis seems not to be effective in improving the clinical outcome of an acute attack of hypertriglyceridemic pancreatitis [8]. Beyond the dietary management and usual pharmacologic therapies, some new genetic treatments are emerging to directly target the driver mutations of the disease [9]. This new approach is certainly promising, but extremely expensive and lacking long-term safety data [10,11].
| Titolo: | Gene targeting for chylomicronemia syndrome: The brave new world. | |
| Autore/i: | Fogacci F; Cicero AF. | |
| Autore/i Unibo: | ||
| Anno: | 2018 | |
| Rivista: | ||
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.atherosclerosis.2017.12.017 | |
| Abstract: | Familial chylomicronemia syndrome (FCS) is caused by homozygous or compound heterozygous mutations in the lipoprotein lipase gene (LPL) or its cofactors. Historically, the syndrome has been considered non-atherogenic for the low levels of low-density lipoprotein cholesterol (LDL-C), even though premature atherosclerosis has been hypothesized in FCS subjects as a consequence of a defective lipolysis [1]. In this issue of Atherosclerosis, Teramoto and collaborators clinically characterized eight unrelated patients affected by FCS and performed a targeted next-generation sequencing on a panel of 4813 genes associated with the phenotypes of interest. All subjects exhibited lactescent or cream-layer serum and three of them had a history of recurrent acute pancreatitis. Teramoto et al. identified four pathogenic (or likely pathogenic) mutations in the LPL gene (including one novel mutation and a variant of uncertain significance) and suggested that atherosclerotic disease may not be accelerated by hyperchylomicronemia [2]. Atherosclerotic lesions are not considered in the diagnostic algorithm for FCS, lately proposed by Stroes et al. [3], even though loss-of-function variants in the angiopoietin-like 3 (ANGPTL3) gene (secondly resulting in the inhibition of LPL activity) have been recently associated with a lower incidence of cardiovascular disease [4]. Certainly this study's sample size is commensurate with the rarity of the disease, though it is way too small to allow us to make statistically significant inferences going beyond some justified clinical suggestions. Hence the importance to increase the current knowledge about FCS of a global, multicenter and prospective observational registry, following for a long period of time the natural course of the disease and clinical outcomes of affected individuals [5]. Nowadays, FCS has an estimated prevalence in the population of 1:1.000.000 [6], with well-recognized major effects on both physical and mental health. The consistently high triglycerides levels can result in clinically relevant manifestations including severe abdominal pain and acute pancreatitis, being potentially fatal or leading to pancreatic damage and permanent exocrine or endocrine insufficiency [7]. The IN-FOCUS study, examining the impact of chylomicronemia on FCS patients' lives, has highlighted another aspect of the disease. FCS has a major impact on quality of life, also significantly influencing career choice and employment status of the patients, as a result of the chances of having a pain attack anytime [7]. LPL deficiency (LPL-D) patients show a bland or even absent response to the traditional lipid-lowering drugs, such as fibrates and omega-3 acid ethyl esters. At the same time, plasmapheresis seems not to be effective in improving the clinical outcome of an acute attack of hypertriglyceridemic pancreatitis [8]. Beyond the dietary management and usual pharmacologic therapies, some new genetic treatments are emerging to directly target the driver mutations of the disease [9]. This new approach is certainly promising, but extremely expensive and lacking long-term safety data [10,11]. | |
| Data stato definitivo: | 2018-02-19T09:59:07Z | |
| Appare nelle tipologie: | 1.01 Articolo in rivista |
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