儿童遗传性胰腺炎的研究进展

于晓政; 吴捷

doi:10.12449/JCH240833

儿童遗传性胰腺炎的研究进展

DOI: 10.12449/JCH240833

于晓政,
吴捷^, ,

国家儿童医学中心，首都医科大学附属北京儿童医院消化科，北京 100045

基金项目:

北京市医院管理中心“登峰”人才培养计划 (DFL20221003)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：于晓政负责查阅文献，资料分析，撰写论文，修改论文；吴捷负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
吴捷， wujie@bch.com.cn （ORCID： 0000-0003-4028-6173）

计量
- 文章访问数: 163
- HTML全文浏览量: 84
- PDF下载量: 17
- 被引次数: 0
出版历程
- 收稿日期: 2023-11-22
- 录用日期: 2024-01-02
- 出版日期: 2024-08-25

Research advances in hereditary pancreatitis in children

Xiaozheng YU,
Jie WU^{,
,}

Department of Gastroenterology，Beijing Children’s Hospital，Capital Medical University，National Center for Children’s Health，Beijing 100045，China

Research funding:

Beijing Hospitals Authority’s Ascent Plan (DFL20221003)

More Information

Corresponding author: WU Jie， wujie@bch.com.cn （ORCID： 0000-0003-4028-6173）

摘要

摘要: 遗传性胰腺炎是儿童胰腺炎的主要致病因素之一，成年后癌变风险高。本文综述了遗传性胰腺炎的研究进展，包括历史发展、流行病学、致病机制及相关致病基因、临床特征与诊断及治疗等，旨在为延缓儿童遗传性胰腺炎疾病进程及基础研究提供新的参考信息。
- 遗传性胰腺炎 /
- 体征和症状 /
- 治疗学 /
- 儿童
Abstract: Hereditary pancreatitis （HP） is one of the major causes of pancreatitis in children and has a high risk of carcinogenesis after they become adults. This article reviews the recent research advances in HP， including historical development， epidemiology， pathogenic mechanism， and related pathogenic genes， clinical features， and diagnosis and treatment， in order to provide new reference information for delaying the progression of HP in children and conducting related basic research.
- Hereditary Pancreatitis /
- Signs and Symptoms /
- Therapeutics /
- Child

HTML全文

表 1 不同年龄段CP患儿胰酶替代治疗推荐剂量

Table 1. Commended pancreatic enzyme replacement therapy dosing for children with chronic pancreatitis-associated exocrine pancreatic insufficiency

年龄	胰酶剂量
<1岁	每120 mL配方奶或母乳中加人2 000～4 000 U脂肪酶，或喂养膳食中每克脂肪含约2 000 U脂肪酶
≥1岁～4岁	喂养膳食中每克脂肪需含2 000～4 000 U脂肪酶，根据需要调整剂量，每日最大剂量为10 000 U脂肪酶/kg
≥4岁	每餐从500 U脂肪酶/kg开始，逐渐增加剂量至每餐1 000～2 500 U脂肪酶/kg，或每日10 000 U脂肪酶/kg，或喂养膳食中每克脂肪需含2 000～4 000 U脂肪酶

下载: 导出CSV

参考文献(49)

[1]	LE COSQUER G, MAULAT C, BOURNET B, et al. Pancreatic cancer in chronic pancreatitis: Pathogenesis and diagnostic approach[J]. Cancers(Basel), 2023, 15( 3): 761. DOI: 10.3390/cancers15030761.
[2]	TAN M, SCHAFFALITZKY de MUCKADELL OB, JØRGENSEN MT. Hereditary pancreatitis[J]. Ugeskr Laeger, 2020, 182( 7): V 11190676.
[3]	COLLETT RW, KENNEDY RL. Chronic relapsing pancreatitis associated with hyperlipemia in an eight year old boy[J]. Proc Staff Meet Mayo Clin, 1948, 23( 7): 158- 162.
[4]	COMFORT MW, STEINBERG AG. Pedigree of a family with hereditary chronic relapsing pancreatitis[J]. Gastroenterology, 1952, 21( 1): 54- 63.
[5]	KEIM V, BAUER N, TEICH N, et al. Clinical characterization of patients with hereditary pancreatitis and mutations in the cationic trypsinogen gene[J]. Am J Med, 2001, 111( 8): 622- 626. DOI: 10.1016/s0002-9343(01)00958-5.
[6]	PAOLINI O, HASTIER P, BUCKLEY M, et al. The natural history of hereditary chronic pancreatitis: a study of 12 cases compared to chronic alcoholic pancreatitis[J]. Pancreas, 1998, 17( 3): 266- 271. DOI: 10.1097/00006676-199810000-00007.
[7]	LE BODIC L, SCHNEE M, GEORGELIN T, et al. An exceptional genealogy for hereditary chronic pancreatitis[J]. Dig Dis Sci, 1996, 41( 7): 1504- 1510. DOI: 10.1007/BF02088580.
[8]	WHITCOMB DC, PRESTON RA, ASTON CE, et al. A gene for hereditary pancreatitis maps to chromosome 7q35[J]. Gastroenterology, 1996, 110( 6): 1975- 1980. DOI: 10.1053/gast.1996.v110.pm8964426.
[9]	WHITCOMB DC, GORRY MC, PRESTON RA, et al. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene[J]. Nat Genet, 1996, 14( 2): 141- 145. DOI: 10.1038/ng1096-141.
[10]	FÉREC C, RAGUÉNÈS O, SALOMON R, et al. Mutations in the cationic trypsinogen gene and evidence for genetic heterogeneity in hereditary pancreatitis[J]. J Med Genet, 1999, 36( 3): 228- 232.
[11]	REBOURS V, BOUTRON-RUAULT MC, SCHNEE M, et al. The natural history of hereditary pancreatitis: a national series[J]. Gut, 2009, 58( 1): 97- 103. DOI: 10.1136/gut.2008.149179.
[12]	LI MY, YANG J. Research advances in hereditary pancreatitis[J/CD]. Chin J Gastrointest Endosc(Electronic Editon), 2018, 5( 2): 87- 92. DOI: 10.3877/cma.j.issn.2095-7157.2018.02.010. 李明阳, 杨晶. 遗传性胰腺炎的研究进展[J/CD]. 中华胃肠内镜电子杂志, 2018, 5( 2): 87- 92. DOI: 10.3877/cma.j.issn.2095-7157.2018.02.010.
[13]	SULTAN M, WERLIN S, VENKATASUBRAMANI N. Genetic prevalence and characteristics in children with recurrent pancreatitis[J]. J Pediatr Gastroenterol Nutr, 2012, 54( 5): 645- 650. DOI: 10.1097/MPG.0b013e31823f0269.
[14]	WANG W, SUN XT, WENG XL, et al. Comprehensive screening for PRSS1, SPINK1, CFTR, CTRC and CLDN2 gene mutations in Chinese paediatric patients with idiopathic chronic pancreatitis: A cohort study[J]. BMJ Open, 2013, 3( 9): e003150. DOI: 10.1136/bmjopen-2013-003150.
[15]	SZABÓ A, SAHIN-TÓTH M. Increased activation of hereditary pancreatitis-associated human cationic trypsinogen mutants in presence of chymotrypsin C[J]. J Biol Chem, 2012, 287( 24): 20701- 20710. DOI: 10.1074/jbc.M112.360065.
[16]	GORRY MC, GABBAIZEDEH D, FUREY W, et al. Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis[J]. Gastroenterology, 1997, 113( 4): 1063- 1068. DOI: 10.1053/gast.1997.v113.pm9322498.
[17]	SUZUKI M, MINOWA K, NAKANO S, et al. Genetic abnormalities in pancreatitis: An update on diagnosis, clinical features, and treatment[J]. Diagnostics(Basel), 2020, 11( 1): 31. DOI: 10.3390/diagnostics11010031.
[18]	KUME K, MASAMUNE A, ARIGA H, et al. Do genetic variants in the SPINK1 gene affect the level of serum PSTI?[J]. J Gastroenterol, 2012, 47( 11): 1267- 1274. DOI: 10.1007/s00535-012-0590-3.
[19]	SCHNEIDER A. Serine protease inhibitor kazal type 1 mutations and pancreatitis[J]. Clin Lab Med, 2005, 25( 1): 61- 78. DOI: 10.1016/j.cll.2004.12.005.
[20]	FELDERBAUER P, HOFFMANN P, EINWÄCHTER H, et al. A novel mutation of the calcium sensing receptor gene is associated with chronic pancreatitis in a family with heterozygous SPINK1 mutations[J]. BMC Gastroenterol, 2003, 3: 34. DOI: 10.1186/1471-230X-3-34.
[21]	BEER S, ZHOU J, SZABÓ A, et al. Comprehensive functional analysis of chymotrypsin C(CTRC) variants reveals distinct loss-of-function mechanisms associated with pancreatitis risk[J]. Gut, 2013, 62( 11): 1616- 1624. DOI: 10.1136/gutjnl-2012-303090.
[22]	FINK EN, KANT JA, WHITCOMB DC. Genetic counseling for nonsyndromic pancreatitis[J]. Gastroenterol Clin North Am, 2007, 36( 2): 325- 333, ix. DOI: 10.1016/j.gtc.2007.03.007.
[23]	PANCHOO AV, VANNESS GH, RIVERA-RIVERA E, et al. Hereditary pancreatitis: An updated review in pediatrics[J]. World J Clin Pediatr, 2022, 11( 1): 27- 37. DOI: 10.5409/wjcp.v11.i1.27.
[24]	HASAN A, MOSCOSO DI, KASTRINOS F. The Role of genetics in pancreatitis[J]. Gastrointest Endosc Clin N Am, 2018, 28( 4): 587- 603. DOI: 10.1016/j.giec.2018.06.001.
[25]	WHITCOMB DC, LARUSCH J, KRASINSKAS AM, et al. Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis[J]. Nat Genet, 2012, 44( 12): 1349- 1354. DOI: 10.1038/ng.2466.
[26]	MUDDANA V, LAMB J, GREER JB, et al. Association between calcium sensing receptor gene polymorphisms and chronic pancreatitis in a US population: Role of serine protease inhibitor Kazal 1type and alcohol[J]. World J Gastroenterol, 2008, 14( 28): 4486- 4491. DOI: 10.3748/wjg.14.4486.
[27]	LUO X, WU ZX, LIU QC, et al. Clinical and hereditary characteristics of hereditary pancreatitis: An analysis of 13 cases[J]. World Chin J Dig, 2008, 16( 19): 2188- 2190. DOI: 10.3969/j.issn.1009-3079.2008.19.023. 骆休, 吴志雄, 刘奇才, 等. 遗传性胰腺炎临床和遗传特点分析13例[J]. 世界华人消化杂志, 2008, 16( 19): 2188- 2190. DOI: 10.3969/j.issn.1009-3079.2008.19.023.
[28]	WANG ZK, LI W. Progress in the diagnosis and treatment of hereditary pancreatitis[J]. Chin J Gastroenterol Hepatol, 2019, 28( 6): 711- 713. DOI: 10.3969/j.issn.1006-5709.2019.06.026. 王子恺, 李闻. 遗传性胰腺炎诊治进展[J]. 胃肠病学和肝病学杂志, 2019, 28( 6): 711- 713. DOI: 10.3969/j.issn.1006-5709.2019.06.026.
[29]	KOLODZIEJCZYK E, JURKIEWICZ E, PERTKIEWICZ J, et al. MRCP versus ERCP in the evaluation of chronic pancreatitis in children: Which is the better choice?[J]. Pancreas, 2016, 45( 8): 1115- 1119. DOI: 10.1097/MPA.0000000000000644.
[30]	GORDON K, CONWAY J, EVANS J, et al. EUS and EUS-guided interventions alter clinical management in children with digestive diseases[J]. J Pediatr Gastroenterol Nutr, 2016, 63( 2): 242- 246. DOI: 10.1097/MPG.0000000000001101.
[31]	ELLIS I, LERCH MM, WHITCOMB DC, et al. Genetic testing for hereditary pancreatitis: Guidelines for indications, counselling, consent and privacy issues[J]. Pancreatology, 2001, 1( 5): 405- 415. DOI: 10.1159/000055840.
[32]	WANG ZP, JING GX, LUO HH, et al. Efficacy and safety of aggressive fluid resuscitation versus conventional fluid resuscitation in early treatment of acute pancreatitis: A Meta-analysis[J]. J Clin Hepatol, 2023, 39( 9): 2158- 2168. DOI: 10.3969/j.issn.1001-5256.2023.09.019. 王张鹏, 景光旭, 罗欢欢, 等. 早期积极液体复苏与常规液体复苏治疗急性胰腺炎效果及安全性的Meta分析[J]. 临床肝胆病杂志, 2023, 39( 9): 2158- 2168. DOI: 10.3969/j.issn.1001-5256.2023.09.019.
[33]	SMIT M, BUDDINGH KT, BOSMA B, et al. Abdominal compartment syndrome and intra-abdominal ischemia in patients with severe acute pancreatitis[J]. World J Surg, 2016, 40( 6): 1454- 1461. DOI: 10.1007/s00268-015-3388-7.
[34]	ZHAO H, HAN Y, PENG KR, et al. Nasogastric or nasojejunal feeding in pediatric acute pancreatitis: A randomized controlled trial[J]. World J Pediatr, 2021, 17( 5): 536- 543. DOI: 10.1007/s12519-021-00441-0.
[35]	ZHU GY, WANG CM, LIAO SY, et al. Interpretation of clinical nutrition guidelines to acute and chronic pancreatitis by the European Society for Clinical Nutrition and Metabolism in 2020[J]. Chin J Pract Surg, 2020, 40( 11): 1259- 1262. DOI: 10.19538/j.cjps.issn1005-2208.2020.11.08. 朱桂英, 王长淼, 廖诗瑶, 等. 2020年《欧洲临床营养和代谢学会急慢性胰腺炎临床营养指南》解读[J]. 中国实用外科杂志, 2020, 40( 11): 1259- 1262. DOI: 10.19538/j.cjps.issn1005-2208.2020.11.08.
[36]	Section of Hepatobiliary Surgery, Branch of Pediatric Surgery, Chinese Medical Association. Expert consensus on diagnosing and treating chronic pancreatitis in children(2023)[J]. Chin J Pediatr Surg, 2023, 44( 7): 577- 585. DOI: 10.3760/cma.j.cn421158-20230111-00009. 中华医学会小儿外科学分会肝胆外科学组. 小儿慢性胰腺炎诊断与治疗专家共识(2023)[J]. 中华小儿外科杂志, 2023, 44( 7): 577- 585. DOI: 10.3760/cma.j.cn421158-20230111-00009.
[37]	ZELLO GA. Dietary reference intakes for the macronutrients and energy: Considerations for physical activity[J]. Appl Physiol Nutr Metab, 2006, 31( 1): 74- 79. DOI: 10.1139/h05-022.
[38]	MATEL JL. Nutritional management of cystic fibrosis[J]. JPEN J Parenter Enteral Nutr, 2012, 36( 1 Suppl): 60S- 67S. DOI: 10.1177/0148607111420156.
[39]	ARVANITAKIS M, OCKENGA J, BEZMAREVIC M, et al. ESPEN guideline on clinical nutrition in acute and chronic pancreatitis[J]. Clin Nutr, 2020, 39( 3): 612- 631. DOI: 10.1016/j.clnu.2020.01.004.
[40]	HEIJERMAN HG, LAMERS CB, BAKKER W. Omeprazole enhances the efficacy of pancreatin(pancrease) in cystic fibrosis[J]. Ann Intern Med, 1991, 114( 3): 200- 201. DOI: 10.7326/0003-4819-114-3-200.
[41]	FREEMAN AJ, MAQBOOL A, BELLIN MD, et al. Medical management of chronic pancreatitis in children: A position paper by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Pancreas Committee[J]. J Pediatr Gastroenterol Nutr, 2021, 72( 2): 324- 340. DOI: 10.1097/MPG.0000000000003001.
[42]	LI ZS, WANG W, LIAO Z, et al. A long-term follow-up study on endoscopic management of children and adolescents with chronic pancreatitis[J]. Am J Gastroenterol, 2010, 105( 8): 1884- 1892. DOI: 10.1038/ajg.2010.85.
[43]	AGARWAL J, NAGESHWAR REDDY D, TALUKDAR R, et al. ERCP in the management of pancreatic diseases in children[J]. Gastrointest Endosc, 2014, 79( 2): 271- 278. DOI: 10.1016/j.gie.2013.07.060.
[44]	Chronic Pancreatitis Group of Pancreatic Disease Committee of Chinese Medical Doctor Association. Guideline for the diagnosis and treatment of chronic pancreatitis(2018, Guangzhou)[J]. J Clin Hepatol, 2019, 35( 1): 45- 51. DOI: 10.3969/j.issn.1001-5256.2019.01.008. 中国医师协会胰腺病专业委员会慢性胰腺炎专委会. 慢性胰腺炎诊治指南(2018, 广州)[J]. 临床肝胆病杂志, 2019, 35( 1): 45- 51. DOI: 10.3969/j.issn.1001-5256.2019.01.008.
[45]	KOHOUTOVA D, TRINGALI A, PAPPARELLA G, et al. Endoscopic treatment of chronic pancreatitis in pediatric population: Long-term efficacy and safety[J]. United European Gastroenterol J, 2019, 7( 2): 270- 277. DOI: 10.1177/2050640618817699.
[46]	QIN XM, ZHANG J, YU FH, et al. Application of endoscopic retrograde cholangiopancreatography on diagnosis and treatment of pediatric chronic pancreatitis[J]. Chin Pediatr Emerg Med, 2023, 30( 7): 504- 507. DOI: 10.3760/cma.j.issn.1673-4912.2023.07.006. 秦秀敏, 张晶, 于飞鸿, 等. 内镜下逆行胰胆管造影术在儿童慢性胰腺炎中的应用价值[J]. 中国小儿急救医学, 2023, 30( 7): 504- 507. DOI: 10.3760/cma.j.issn.1673-4912.2023.07.006.
[47]	RAPHAEL KL, WILLINGHAM FF. Hereditary pancreatitis: Current perspectives[J]. Clin Exp Gastroenterol, 2016, 9: 197- 207. DOI: 10.2147/CEG.S84358.
[48]	FU HX, XU C, TIAN Y, et al. Curative effect of total pancreatectomy and autologous islet transplantation for chronic pancreatitis in children[J/OL]. Chin J Hepat Surg(Electronic Edition), 2022, 11( 2): 118- 122. DOI: 10.3877/cma.j.issn.2095-3232.2022.02.002. 傅红兴, 许昌, 田阳, 等. 全胰腺切除联合自体胰岛移植治疗儿童慢性胰腺炎疗效[J/OL]. 中华肝脏外科手术学电子杂志, 2022, 11( 2): 118- 122. DOI: 10.3877/cma.j.issn.2095-3232.2022.02.002.
[49]	SUN ZL. Research progress of total pancreatectomy with islet autotransplantation for chronic pancreatitis or recurrent acute pancreatitis[J]. Chin J Dig Surg, 2023, 22( 5): 599- 603. DOI: 10.3760/cma.j.cn115610-20230406-00155. 孙兆黎. 全胰腺切除胰岛自体移植治疗慢性或复发性急性胰腺炎的研究进展[J]. 中华消化外科杂志, 2023, 22( 5): 599- 603. DOI: 10.3760/cma.j.cn115610-20230406-00155.