合并炎症性肠病的糖原累积病-Ⅰb型5例患儿SGLT2抑制剂治疗效果分析

doi:10.12372/jcp.2023.22e0095

Abstract

Abstract:

Objective To analyze the therapeutic effect of a sodium-glucose co-transporter 2 (SGLT2) inhibitor in five pediatric patients with glycogen storage disease type Ⅰb (GSD-Ⅰb) and inflammatory bowel disease (IBD). Methods Changes in clinical manifestations and laboratory tests of five pediatric GSD-Ⅰb patients with IBD before and after the administration of a SGLT2 inhibitor from 2021 to 2022 were analyzed retrospectively. Results The median age of IBD onset was 5.0 years old. All five patients presented with oral ulcers, abdominal pain, diarrhea and perianal abscess. Before the administration of the SGLT2 inhibitor, the median pediatric Crohn’s disease activity index (PCDAI) was 55.0. After the treatment [median length of treatment: 12.0 months, median dose at the last follow-up: 0.31 mg/(kg·d)], the median PCDAI (10.0) was significantly decreased (P=0.043), and all the patients achieved clinical response. During the treatment, 2 patients developed hypoglycemia and 4 patients developed pruritus in perineum or urethral orifice. Two novel SLC37A4 variants were identified (c.2delT, c.1065delG) and c.446G>A (p.G149E) was a hotspot variant (70%). Conclusions The SGLT2 inhibitor can significantly and safely reduce the disease activity of IBD in pediatric GSD-Ⅰb patients.

Key words: glycogen storage disease type Ⅰb, SLC37A4 gene, inflammatory bowel disease, neutropenia, SGLT2 inhibitor

XIA Yu, GE Wensong, DU Taozi, GONG Zizhen, XIAO Bing, LIANG Lili, WANG Ruifang, YANG Yi, QIU Wenjuan. Therapeutic efficacy of an SGLT2 inhibitor in five pediatric patients with glycogen storage disease type Ⅰb and inflammatory bowel disease[J].Journal of Clinical Pediatrics, 2023, 41(4): 294-299.

Figures/Tables 3

References 21

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患儿	父源			母源
患儿	核苷酸改变（NM_001164277）	氨基酸改变	ACMG评分	核苷酸改变（NM_001164277）	氨基酸改变	ACMG评分
P1	c.446G>A	p.G149E	P	c.446G>A	p.G149E	P
P2	c.446G>A	p.G149E	P	c.446G>A	p.G149E	P
P3	c.446G>A	p.G149E	P	c.446G>A	p.G149E	P
P4	c.357_358insC	p.C121MfsX10	P	c.446G>A	p.G149E	P
P5	c.2delT^1）	/	LP	c.1065delG^1）	p.S356VfsX47	LP

项目	初诊中位数	SGLT2抑制剂治疗前	SGLT2抑制剂治疗后	Z值	P
呼吸道感染/次·年^-1	6.0(2.0~12.0)	5.0(3.0~7.5)	3.0(1.0~4.0)	5.158	0.076
ALT/U·L^-1	132.0(92.5~389.0)	31.0(13.0~40.5)	29.0(12.0~39.0)	7.600	0.022
AST/ U·L^-1	386.0(139.5~1267.0)	26.0(16.5~28.5)	16.0(9.5~31.0)	8.400	0.015
GGT/ U·L^-1	370.0(56.5~535.5)	22.0(18.0~43.0)	23.0(16.0~36.5)	7.600	0.022
乳酸/mmol·L^-1	8.8(6.2~10.1)	3.1(1.8~3.7)	2.4(2.1~3.8)	7.600	0.022
尿酸SDS	3.53(－0.42~6.64)	2.04(－0.22~4.97)	－0.20(－0.68~1.37)	2.800	0.247
TG/mmol·L^-1	4.05(3.08~5.52)	2.27(1.41~3.64)	2.56(1.76~3.48)	7.429	0.024
TC/mmol·L^-1	4.82(2.95~5.74)	4.97(3.31~5.59)	3.79(3.64~5.70)	0.667	0.717
ANC×10⁹·L^-1	0.97(0.70~1.22)	0.75(0.40~1.69)	1.63(0.48~1.77)	1.600	0.449
Hb/g·L^-1	99.0(90.5~104.0)	99.0(87.5~116.0)	128.0(116.0~145.0)	8.400	0.015
身高SDS	－1.58(－2.11~0.03)	－2.39(－3.76~－2.30)	－2.14(－3.59~－1.50)	6.400	0.041
BMI SDS	0.49(－0.26~1.59)	0.23(－1.09~1.14)	0.20(－0.34~1.33)	0.400	0.819

项目	P1	P2	P3	P4	P5	M（P₂₅~P₇₅）
IBD发作年龄/岁	1.0	6.0	5.0	1.0	8.0	5.0(1.0~7.0)
行肠镜检查年龄/岁	6.8	13.0	6.3	6.0	17.0	6.8(6.2~15.0)
口腔溃疡发作年龄/岁	1.0	0.6	0.5	1.0	5.0	1.0(0.6~3.0)
腹痛发作年龄/岁	2.0	6.0	5.0	3.0	8.0	5.0(2.5~7.0)
腹泻发作年龄/岁	0.6	6.0	3.5	0.8	8.0	3.5(0.7~7.0)
肛周脓肿发作年龄/岁	0.6	10.0	6.0	1.0	10.0	6.0(0.8~10.0)
SGLT2抑制剂初剂量/mg·kg^-1·d^-1	0.2	0.16	0.16	0.36	0.22	0.20(0.16~0.29)
SGLT2抑制剂终剂量/mg·kg^-1·d^-1	0.5	0.31	0.39	0.28	0.29	0.31(0.29~0.45)
SGLT2抑制剂治疗时长/月	12	9	13	12	7	12.0(8.0~12.5)
SGLT2抑制剂治疗前PCDAI	65.0	35.0	60.0	45.0	55.0	55.0(40.0~62.5)
SGLT2抑制剂治疗后PCDAI	17.5	10.0	10.0	35.0	10.0	10.0(10.0~26.3)

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Therapeutic efficacy of an SGLT2 inhibitor in five pediatric patients with glycogen storage disease type Ⅰb and inflammatory bowel disease

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