二例GCK基因突变致先天性高胰岛素性低血糖症的诊疗和基因检测分析

doi:10.16288/j.yczz.22-226

[an error occurred while processing this directive]

Hereditas(Beijing) ›› 2022, Vol. 44 ›› Issue (11): 1056-1062.doi: 10.16288/j.yczz.22-226

• Genetic Resource • Previous Articles Next Articles

Diagnosis, treatment and genetic analysis of two cases of congenital hyperinsulinemic hypoglycemia caused by GCK gene mutation

Ruizhi Jiajue(), Cheng Xiao(), Yiwen Liu, Ran Li, Huabing Zhang, Miao Yu()

Department of Endocrinology, Key Laboratory of Endocrinology, National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China

Received:2022-06-30 Revised:2022-09-06 Online:2022-11-20 Published:2022-09-29
Contact: Yu Miao E-mail:jjrz@pumch.cn;jz_xiaocheng@163.com;yumiaoxh@163.com
Supported by:
the National Natural Science Foundation of China(82170855);the National Key Research and Development Program(2020YFC2004505);the National Key Research and Development Program(2018YFC2001105)

Abstract

Abstract:

Congenital hyperinsulinemia (CHI) is a heterogeneous disorder characterized by persistent hypoglycemia due to inappropriate insulin secretion. A total of 15 gene mutations have already been reported to be associated with CHI. Among them, CHI caused by the GCK mutation is named GCK-CHI, which is considered to be a rare form of CHI. Here, we reported two cases of GCK-CHI diagnosed by genetic testing and summarized the clinical characteristics. In patients with recurrent or persistent hypoglycemia, CHI should be taken into consideration. Genetic testing should be perfomed in these patients to avoid misdiagnosis and provide accurate intervention, thus to improve prognosis.

Key words: congenital hyperinsulinemic, hypoglycemia, GCK gene mutation

Ruizhi Jiajue, Cheng Xiao, Yiwen Liu, Ran Li, Huabing Zhang, Miao Yu. Diagnosis, treatment and genetic analysis of two cases of congenital hyperinsulinemic hypoglycemia caused by GCK gene mutation[J]. Hereditas(Beijing), 2022, 44(11): 1056-1062.

Figures/Tables 3

References 30

[1]	Galcheva S, Demirbilek H, Al-Khawaga S, Hussain K. The genetic and molecular mechanisms of congenital hyperinsulinism. Front Endocrinol (Lausanne), 2019, 10: 111. doi: 10.3389/fendo.2019.00111
[2]	Saint-Martin C, Arnoux JB, de Lonlay P, Bellanné- Chantelot C. KATP channel mutations in congenital hyperinsulinism. Semin Pediatr Surg, 2011, 20(1): 18-22. doi: 10.1053/j.sempedsurg.2010.10.012 pmid: 21185999
[3]	Lu M, Li CH. Nutrient sensing in pancreatic islets: lessons from congenital hyperinsulinism and monogenic diabetes. Ann N Y Acad Sci, 2018, 1411(1): 65-82. doi: 10.1111/nyas.13448
[4]	Glaser B, Kesavan P, Heyman M, Davis E, Cuesta A, Buchs A, Stanley CA, Thornton PS, Permutt MA, Matschinsky FM, Herold KC. Familial hyperinsulinism caused by an activating glucokinase mutation. N Engl J Med, 1998, 338(4): 226-230. doi: 10.1056/NEJM199801223380404
[5]	Osbak KK, Colclough K, Saint-Martin C, Beer NL, Bellanné-Chantelot C, Ellard S, Gloyn AL. Update on mutations in glucokinase (GCK), which cause maturity- onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia. Hum Mutat, 2009, 30(11): 1512-1526. doi: 10.1002/humu.21110 pmid: 19790256
[6]	Christesen HBT, Jacobsen BB, Odili S, Buettger C, Cuesta-Munoz A, Hansen T, Brusgaard K, Massa O, Magnuson MA, Shiota C, Matschinsky FM, Barbetti F. The second activating glucokinase mutation (A456V): implications for glucose homeostasis and diabetes therapy. Diabetes, 2002, 51(4): 1240-1246. doi: 10.2337/diabetes.51.4.1240 pmid: 11916951
[7]	Galcheva S, Al-Khawaga S, Hussain K. Diagnosis and management of hyperinsulinaemic hypoglycaemia. Best Pract Res Clin Endocrinol Metab, 2018, 32(4): 551-573. doi: S1521-690X(18)30082-4 pmid: 30086874
[8]	Palladino AA, Bennett MJ, Stanley CA. Hyperinsulinism in infancy and childhood: when an insulin level is not always enough. Clin Chem, 2008, 54(2): 256-263. pmid: 18156285
[9]	Ferrara C, Patel P, Becker S, Stanley CA, Kelly A. Biomarkers of insulin for the diagnosis of hyperinsulinemic hypoglycemia in infants and children. J Pediatr, 2016, 168: 212-219. doi: 10.1016/j.jpeds.2015.09.045
[10]	Froguel P, Vaxillaire M, Sun F, Velho G, Zouali H, Butel MO, Lesage S, Vionnet N, Clément K, Fougerousse F, Tanizawa Y, Weissenbach J, Beckmann JS, Lathrop GM, Passa P, Permutt MA, Cohen D. Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin- dependent diabetes mellitus. Nature, 1992, 356(6365): 162-164. doi: 10.1038/356162a0
[11]	Iynedjian PB, Möbius G, Seitz HJ, Wollheim CB, Renold AE. Tissue-specific expression of glucokinase: identification of the gene product in liver and pancreatic islets. Proc Natl Acad Sci USA, 1986, 83(7): 1998-2001. doi: 10.1073/pnas.83.7.1998
[12]	Nessa A, Rahman SA, Hussain K. Hyperinsulinemic hypoglycemia-the molecular mechanisms. Front Endocrinol (Lausanne), 2016, 7: 29.
[13]	Christesen HBT, Tribble ND, Molven A, Siddiqui J, Sandal T, Brusgaard K, Ellard S, Njølstad PR, Alm J, Jacobsen BB, Hussain K, Gloyn AL. Activating glucokinase (GCK) mutations as a cause of medically responsive congenital hyperinsulinism: prevalence in children and characterisation of a novel GCK mutation. Eur J Endocrinol, 2008, 159(1): 27-34. doi: 10.1530/EJE-08-0203 pmid: 18450771
[14]	Gilis-Januszewska A, Bogusławska A, Kowalik A, Rzepka E, Soczówka K, Przybylik-Mazurek E, Głowa B, Hubalewska-Dydejczyk A. Hyperinsulinemic hypoglycemia in three generations of a family with glucokinase activating mutation, c.295T>C (p.Trp99Arg). Genes (Basel), 2021, 12(10): 1566. doi: 10.3390/genes12101566
[15]	Koneshamoorthy A, Seniveratne-Epa D, Calder G, Sawyer M, Kay TWH, Farrell S, Loudovaris T, Mariana L, McCarthy D, Lyu R, Liu X, Thorn P, Tong J, Chin LK, Zacharin M, Trainer A, Taylor S, MacIsaac RJ, Sachithanandan N, Thomas HE, Krishnamurthy B. Case report: hypoglycemia due to a novel activating glucokinase variant in an adult-a molecular approach. Front Endocrinol (Lausanne), 2022, 13: 842937.
[16]	Sternisha SM, Liu PL, Marshall AG, Miller BG. Mechanistic origins of enzyme activation in human glucokinase variants associated with congenital hyperinsulinism. Biochemistry, 2018, 57(10): 1632-1639. doi: 10.1021/acs.biochem.8b00022 pmid: 29425029
[17]	Gloyn AL, Noordam K, Willemsen MAAP, Ellard S, Lam WWK, Campbell IW, Midgley P, Shiota C, Buettger C, Magnuson MA, Matschinsky FM, Hattersley AT. Insights into the biochemical and genetic basis of glucokinase activation from naturally occurring hypoglycemia mutations. Diabetes, 2003, 52(9): 2433-2340. doi: 10.2337/diabetes.52.9.2433 pmid: 12941786
[18]	Kamata K, Mitsuya M, Nishimura T, Eiki JI, Nagata Y. Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase. Structure, 2004, 12(3): 429-438. pmid: 15016359
[19]	Sayed S, Langdon DR, Odili S, Chen P, Buettger C, Schiffman AB, Suchi M, Taub R, Grimsby J, Matschinsky FM, Stanley CA. Extremes of clinical and enzymatic phenotypes in children with hyperinsulinism caused by glucokinase activating mutations. Diabetes, 2009, 58(6): 1419-1427. doi: 10.2337/db08-1792 pmid: 19336674
[20]	Whittington AC, Larion M, Bowler JM, Ramsey KM, Brüschweiler R, Miller BG. Dual allosteric activation mechanisms in monomeric human glucokinase. Proc Natl Acad Sci USA, 2015, 112(37): 11553-11558. doi: 10.1073/pnas.1506664112
[21]	Martínez R, Gutierrez-Nogués Á, Fernández-Ramos C, Velayos T, Vela A, Spanish Congenital Hyperinsulinism Group, Navas MÁ, Castaño L. Heterogeneity in phenotype of hyperinsulinism caused by activating glucokinase mutations: a novel mutation and its functional characterization. Clin Endocrinol (Oxf), 2017, 86(6): 778-783. doi: 10.1111/cen.13318
[22]	Maiorana A, Caviglia S, Greco B, Alfieri P, Cumbo F, Campana C, Bernabei SM, Cusmai R, Mosca A, Dionisi- Vici C. Ketogenic diet as elective treatment in patients with drug-unresponsive hyperinsulinemic hypoglycemia caused by glucokinase mutations. Orphanet J Rare Dis, 2021, 16(1): 424. doi: 10.1186/s13023-021-02045-3 pmid: 34635134
[23]	Li LY, Liu SQ, Shi Y, Zheng S, Zhao CC, Zheng XQ. Diagnosis, treatment and genetic analysis of a case of hypoglycemia caused by glucokinase gene mutation. Hereditas(Beijing), 2022, 44(9): 810-818.
	李璐阳, 刘孙强, 施云, 赵成程, 周红文, 郑旭琴. 一例葡萄糖激酶基因突变致低血糖症的诊疗及家系遗传分析. 遗传, 2022, 44(9): 810-818..
[24]	Snider KE, Becker S, Boyajian L, Shyng SL, MacMullen C, Hughes N, Ganapathy K, Bhatti T, Stanley CA, Ganguly A. Genotype and phenotype correlations in 417 children with congenital hyperinsulinism. J Clin Endocrinol Metab, 2013, 98(2): E355-E363. doi: 10.1210/jc.2012-2169
[25]	Hussain K. Diagnosis and management of hyperinsulinaemic hypoglycaemia of infancy. Horm Res, 2008, 69(1): 2-13. pmid: 18059080
[26]	Güemes M, Hussain K. Hyperinsulinemic hypoglycemia. Pediatr Clin North Am, 2015, 62(4): 1017-1036. doi: 10.1016/j.pcl.2015.04.010
[27]	Müller D, Zimmering M, Roehr CC. Should nifedipine be used to counter low blood sugar levels in children with persistent hyperinsulinaemic hypoglycaemia? Arch Dis Child, 2004, 89(1): 83-85. pmid: 14709521
[28]	Mohnike K, Blankenstein O, Pfuetzner A, Pötzsch S, Schober E, Steiner S, Hardy OT, Grimberg A, van Waarde WM. Long-term non-surgical therapy of severe persistent congenital hyperinsulinism with glucagon. Horm Res, 2008, 70(1): 59-64. doi: 10.1159/000129680 pmid: 18493152
[29]	Senniappan S, Alexandrescu S, Tatevian N, Shah P, Arya V, Flanagan S, Ellard S, Rampling D, Ashworth M, Brown RE, Hussain K. Sirolimus therapy in infants with severe hyperinsulinemic hypoglycemia. N Engl J Med, 2014, 370(12): 1131-1137. doi: 10.1056/NEJMoa1310967
[30]	Hernandez-Pampaloni M, Zhuang HM, Fanti S, Alavi A. Positron emission tomography imaging and hyperinsulinism. PET Clin, 2007, 2(3): 377-383. doi: 10.1016/j.cpet.2008.05.003 pmid: 27158017

Metrics

Comments

www.chinagene.cn
备案号：京ICP备09063187号

编号	血糖(mmol/L)	胰岛素 (正常参考值：5.2~17.2 μIU/mL)	C肽 (正常参考值：0.8~4.2 ng/mL)	胰岛素原 (正常参考值：30~180 pg/mL)	尿酮体
患者1	2.0~2.1	7.9~10.5	1.38~1.62	138~176	阴性
患者2	2.5~2.7	3.1~-3.6	0.73-0.97	<2	阴性

患者	染色体位置	外显子	突变位点	突变类型	杂合性	变异评级	遗传方式
1	Chr.7:44149848-44149848	3	NM_000162.5:c.295T>A, p.W99R	错义突变	杂合	可能致病 (PS1+PM1+PM2+PP3)	常染色体显性遗传
2	Chr.7:44152339-44152339	6	NM_000162.5:c.591G>C, p.M197I	错义突变	杂合	可能致病 (PS1+PM1+PM2)	常染色体显性遗传

Diagnosis, treatment and genetic analysis of two cases of congenital hyperinsulinemic hypoglycemia caused by GCK gene mutation

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 3

References 30

Related Articles 2

Recommended Articles

Metrics

Comments

[1]	Luyang Li, Sunqiang Liu, Yun Shi, Chengcheng Zhao, Hongwen Zhou, Xuqin Zheng. Diagnosis, treatment and genetic analysis of a case of hypoglycemia caused by glucokinase gene mutation [J]. Hereditas(Beijing), 2022, 44(9): 810-818.
[2]	Yingyun Gong, Zhenzhen Fu, Hongwen Zhou. Establishment and operation of glucose clamp technique in mice [J]. Hereditas(Beijing), 2022, 44(10): 967-974.