家族性高乳糜微粒血症(FCS)是一组罕见的常染色体隐性遗传性疾病,由编码脂蛋白脂酶的LPL基因变异或参与调控脂蛋白脂酶活性的蛋白编码基因变异引起。明显升高的血浆甘油三酯(TG)水平(通常＞10mmol/L)以及由此引起的发疹性黄色瘤、高脂血症性视网膜病变、脾肿大、复发性腹痛和胰腺炎发作是FCS的主要临床表现,其中胰腺炎是本病威胁患者生命、导致生存质量下降的主要原因,且其发生率及严重程度与血TG水平明显相关。FCS患者使用常规降脂药物通常无效,目前长期严格的极低脂肪饮食是此病的主要治疗方式。通常每日饮食来源的脂肪摄入量占能比需低至10%~15%,同时需保证必需脂肪酸的摄入。FCS的饮食治疗可短时间内降低患者血浆TG水平,并有效预防高TG血症相关并发症的发生,但长期实施和遵循饮食指南的极低脂肪饮食模式仍面临挑战。调查显示,许多患者存在心理及社会生活问题。因此,FCS需要药物治疗、遗传咨询、营养学、心理学等多学科治疗。
Abstract
Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive genetic disorder caused by variations in the LPL gene, which codes for lipoprotein lipase, or in genes coding for proteins that regulate lipoprotein lipase activity. Markedly elevated plasma triglyceride (TG) levels (typically >10mmol/L), along with the resulting rash yellow tumor, retinal hyperlipidemia, splenomegaly, recurrent abdominal pain, and pancreatitis attacks are the main clinical manifestations of FCS. Among them, pancreatitis is the primary life-threatening complication and the main cause of reduced quality of life, with its incidence and severity clearly related to plasma TG levels. Conventional lipid-lowering drugs are typically ineffective in FCS patients. Currently, a long-term strict very low-fat diet is the main treatment for this disease. This usually involves reducing dietary fat intake to 10% - 15% of total energy needs while ensuring adequate intake of essential fatty acids. Dietary management can rapidly lower plasma TG levels and effectively prevent complications related to hypertriglyceridemia. However, maintaining and adhering to such a strict very low-fat diet regimen over the long term remains challenging. Surveys have shown that a large part of patients face psychological and social support issues. Therefore, the treatment of FCS requires interdisciplinary collaboration in pharmacology, genetics, nutrition, psychology, and other fields.
关键词
甘油三酯 /
脂蛋白脂酶 /
乳糜微粒 /
胰腺炎 /
饮食治疗
Key words
triglycerides /
lipoprotein lipase /
chylomicrons /
pancreatitis /
dietary therapy
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Shamsudeen I, Hegele RA.Safety and efficacy of therapies for chylomicronemia[J].Expert Rev Clin Pharmacol,2022,15(4):395-405.
[2] Surendran RP, Visser ME, Heemelaar S,et al.Mutations in LPL,APOC2, APOA5,GPIHBP1 andIMF1 in patients with severe hypertriglyceridaemia[J]. J Intern Med,2012,272(2):185-196.
[3] Hegele RA, Berberich AJ, Ban MR, et al. Clinical and biochemical features of different molecular etiologies of familial chylomicronemia[J]. J Clin Lipidol,2018,12(4):920-927.
[4] Lima JG, Helena C Nobrega L, Moura Bandeira FT,et al. A novel GPIHBP1 mutation related to familial chylomicronemia syndrome: A series of cases[J].Atherosclerosis,2021,322:31-38.
[5] Cao C, Liu Y, Liu L,et al. Identification of a compound heterozygous lmf1 variants in a patient with severe hypertriglyceridemia - Case report and literature review[J].J Atheroscler Thromb,2024,31(7):1106-1111.
[6] Jiang J, Wang Y, Ling Y, et al.A novel APOC2 gene mutation identified in a Chinese patient with severe hypertriglyceridemia and recurrent pancreatitis[J].Lipids Health Dis,2016,15:12.
[7] Perera SD, Wang J, McIntyre AD,et al. Variability of longitudinal triglyceride phenotype in patients heterozygous for pathogenic APOA5 variants[J].J Clin Lipidol,2023,17(5):659-665.
[8] Kuthiroly S, Yesodharan D, Radhakrishnan N,et al. Lipoprotein lipase deficiency[J].Indian J Pediatr,2021,88(2):147-153.
[9] Falko JM. Familialchylomicronemia syndrome: A clinical guide for endocrinologists[J].Endocr Pract,2018,24(8):756-763.
[10] Scherer J, Singh VP, Pitchumoni CS,et al. Issues in hypertriglyceridemic pancreatitis:An update[J].J Clin Gastroenterol, 2014,48(3):195-203.
[11] Wang Q, Wang G, Qiu Z, et al.Elevated serum triglycerides in the prognostic assessment of acute pancreatitis: A systematic review and meta-analysis of observational studies[J]. J Clin Gastroenterol,2017,51(7):586-593.
[12] 何文华,祝荫,朱勇,等. 高TG血症与其他病因所致急性胰腺炎的病情严重程度及预后比较[J].中华医学杂志,2016,96(32):2569-2572.
[13] Pascual I, Sanahuja A, García N,et al. Association of elevated serum triglyceride levels with a more severe course of acute pancreatitis: Cohort analysis of 1457 patients[J].Pancreatology,2019,19(5):623-629.
[14] Gouni-Berthold I, Schwarz J, Berthold HK. Updates in drug treatment of severe hypertriglyceridemia[J].Curr Atheroscler Rep, 2023,25(10):701-709.
[15] Williams L, Rhodes KS, Karmally W, et al.Familial chylomicronemia syndrome: Bringing to life dietary recommendations throughout the life span[J]. J Clin Lipidol,2018,12(4):908-919 .
[16] Williams L, Wilson DP.Editorial commentary: Dietary management of familial chylomicronemia syndrome[J].J Clin Lipidol,2016,10(3):462-465.
[17] Gallo A, Béliard S, D'Erasmo L, et al. Familial chylomicronemia syndrome(FCS): Recent data on diagnosis and treatment[J].Curr Atheroscler Rep,2020,22(11):63.
[18] Xia Y, Zheng W, Du T,et al. Clinical profile, genetic spectrum and therapy evaluation of 19 Chinese pediatric patients with lipoprotein lipase deficiency[J].J Clin Lipidol,2023,17(6):808-817.
[19] Aljouda L, Nagy L, Schulze A. Long-term treatment of lipoprotein lipase deficiency with medium-chain triglyceride-enriched diet: A case series[J].Nutrients,2023,15(16):3535.
[20] Davidson M, Stevenson M, Hsieh A, et al. The burden of familial chylomicronemia syndrome: Results from the global IN-FOCUS study[J]. J Clin Lipidol,2018,12(4):898-907.
PDF(571 KB)
