一例胰腺纤维钙化性糖尿病的诊疗和基因检测分析

doi:10.16288/j.yczz.22-210

遗传 ›› 2022, Vol. 44 ›› Issue (11): 1079-1086.doi: 10.16288/j.yczz.22-210

• 遗传资源 • 上一篇

一例胰腺纤维钙化性糖尿病的诊疗和基因检测分析

沈敏¹(), 顾愹¹, 应长江², 张梅¹, 杨涛¹, 陈阳¹()

1. 南京医科大学第一附属医院内分泌科，南京 210029
2. 徐州医科大学附属医院内分泌科，徐州 221000

收稿日期:2022-06-21 修回日期:2022-09-01 出版日期:2022-11-20 发布日期:2022-09-07
通讯作者: 陈阳 E-mail:drshenmin@163.com;drchenyang@njmu.edu.cn
作者简介:沈敏，在读博士研究生，专业方向：内分泌与代谢病方向。E-mail: drshenmin@163.com
基金资助:
国家自然科学基金项目(81900708);江苏省研究生科研与实践创新计划项目(JX10213850);SDF·甜蜜医生培育项目(2021SD02)

Diagnosis, treatment and genetic analysis of a case with fibrocalculous pancreatic diabetes

Min Shen¹(), Yong Gu¹, Changjiang Ying², Mei Zhang¹, Tao Yang¹, Yang Chen¹()

1. Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
2. Department of Endocrinology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China

Received:2022-06-21 Revised:2022-09-01 Online:2022-11-20 Published:2022-09-07
Contact: Chen Yang E-mail:drshenmin@163.com;drchenyang@njmu.edu.cn
Supported by:
the National Natural Science Foundation of China(81900708);Postgraduate Research & Practice Innovation Program of Jiangsu Province(JX10213850);Sinocare Diabetes Foundation(2021SD02)

摘要/Abstract

摘要：

胰腺纤维钙化性糖尿病(fibrocalculous pancreatic diabetes, FCPD)是一类罕见的、胰腺内、外分泌功能同时发生障碍的特殊类型糖尿病。本文报道了1例FCPD患者的临床资料，该患者自幼年起反复出现腹痛，25岁时诊断为糖尿病，腹部CT见胰腺钙化，基因检测发现SPINK1基因有2个纯合突变(c.194+2T>C和-191-24G>A)。基因检测分析发现其父母为杂合变异，其弟弟为纯合变异，但尚未观察到FCPD的典型表现。结合该病例及国内90例FCPD患者的临床特点汇总分析，建议对体型消瘦、无酮症倾向但胰岛功能较差的分型不明确糖尿病患者，需要考虑FCPD可能性，重视胰腺影像学及基因检测，尽早进行鉴别诊断。本文提高了对FCPD的认识和管理，为该疾病后续致病机制的深入研究与药物干预靶点的筛选充实了临床资料。

关键词: 胰腺纤维钙化, 糖尿病, SPINK1基因, 鉴别诊断

Abstract:

Fibrocalculous pancreatic diabetes (FCPD) is a rare type of diabetes mellitus with both impaired endocrine and exocrine functions of the pancreas. In this report, we presented a case with FCPD, who had recurrent abdominal pain since early childhood and was diagnosed with diabetes mellitus at the age of 25, with pancreatic calcification on abdominal computed tomography (CT) scan. Genetic testing revealed two homozygous mutations in the SPINK1 gene (c.194+2T>C and -191-24G>A). Both the homozygous variants were shared by his unaffected sibling, and the heterozygous variants had been verified on their unaffected parents. Based on this case and 90 other reported cases in China, we retrospectively analyzed the clinical characteristics of FCPD. It is recommended that unclassified diabetic patients with a lean body type, no ketosis tendency but poor islet function should be considered for the possibility of FCPD. Pancreatic imaging and genetic testing may be beneficial for the differential diagnosis. This study improves our understanding and management of FCPD, and also enriches clinical evidence for subsequent research on pathogenic mechanisms and drug target screening.

Key words: pancreatic fibrocalcification, diabetes, SPINK1, differential diagnosis

沈敏, 顾愹, 应长江, 张梅, 杨涛, 陈阳. 一例胰腺纤维钙化性糖尿病的诊疗和基因检测分析[J]. 遗传, 2022, 44(11): 1079-1086.

Min Shen, Yong Gu, Changjiang Ying, Mei Zhang, Tao Yang, Yang Chen. Diagnosis, treatment and genetic analysis of a case with fibrocalculous pancreatic diabetes[J]. Hereditas(Beijing), 2022, 44(11): 1079-1086.

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项目	患者父亲	患者母亲	患者弟弟
年龄	50	52	16
体重指数(kg/m²)	26.2	19.9	29.39
空腹血糖(mmol/L)	5.29	5.11	4.82
餐后1 h血糖(mmol/L)	-	9.26	8.26
餐后2 h血糖(mmol/L)	8.78	9.2	6.53
空腹胰岛素(pmol/L)	70.3	36.8	72
餐后1 h胰岛素(pmol/L)	-	403.4	404.3
餐后2 h胰岛素(pmol/L)	834.6	312.8	678.5
空腹C肽(ng/mL)	2.09	1.8	2.04
餐后1 h C肽(ng/mL)	-	9.47	8.37
餐后2 h C肽(ng/mL)	14.68	11.39	11.21
持续性腹痛	无	无	无
胰腺影像学检查	-	胰腺未见异常	胰腺未见异常

	国内报道	国外报道	本例患者
发病率	<0.001%	0.019%~1.6%	-
地区分布	散在分布，亚热带和北温带为主	热带为主	中国北温带
年龄	16~67	10~30岁多见	25
性别(男%)	64%	43%~70%	男
BMI (kg/m²)	多消瘦	多消瘦	17.17
木薯食用史	20%	常见	否
降糖治疗	胰岛素治疗为主	胰岛素治疗为主	口服药
误诊	>20%	>85%	否
脂肪泻(%)	<30%	24%	否
慢性腹痛(%)	50%	33%	是
胰岛自身抗体	1例GAD阳性	GAD阳性：7.0% ICA阳性：6.3%	IAA阳性后转阴
基因	WFS1基因2号外显子杂合突变： c.139C>T	HLA-DQ9 (A0201-B0303)，DQB1； SPINK1基因最常见	HLA-A2402;3201, DRB10701;1301，SPINK1基因纯合突变：c.194+2T>C与-191-24G>A

一例胰腺纤维钙化性糖尿病的诊疗和基因检测分析

Diagnosis, treatment and genetic analysis of a case with fibrocalculous pancreatic diabetes

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