Association Analysis of Genotype and Phenotype in Fructose-1,6-Bisphosphatase Deficiency: A Case Report and Literature Review

doi:10.12280/gjszjk.20250082

Abstract

Abstract:

Fructose-1,6-bisphosphatase deficiency (FBP1D), a rare inherited metabolic disorder, may lead to severe neurological sequelae if not treated promptly and effectively. We report a case of FBP1D diagnosed through trio-whole exome sequencing (trio-WES). The NM_000507.4(FBP1) c.977T>C variant in this patient has not been reported in China. We summarized and analyzed the genotypic and phenotypic characteristics of 31 Chinese FBP1D patients from literature. The typical clinical manifestations included hypoglycemia, metabolic acidosis, gastrointestinal symptoms, and impaired consciousness, with the infection being the most common triggering factor. Genetic analysis revealed that the c.960dup variant in the FBP1 gene is the most prevalent variant among Chinese patients. Enhancing clinicians′ awareness of FBP1D can facilitate early diagnosis and active intervention, thereby significantly improve patient prognosis.

Key words: Fructose-1,6-diphosphatase deficiency, Hypoglycemia, Acidosis, Whole exome sequencing, FBP1 gene

WANG Hua, XUE Feng, XIONG Fu, NIE Xiao-cheng, LUO Ze-min, ZHU Shu-yao, ZENG Lan, PI Guang-huan. Association Analysis of Genotype and Phenotype in Fructose-1,6-Bisphosphatase Deficiency: A Case Report and Literature Review[J]. Journal of International Reproductive Health/Family Planning, 2025, 44(5): 377-382.

Figures/Tables 4

References 30

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序号	文献	发表年份	患者性别	变异1	变异2	发病诱因			临床表现			发病年龄	酸中毒	神经发育障碍	血糖（mol/L）	患者诊断年龄
序号	文献	发表年份	患者性别	变异1	变异2	感染	水果	空腹	胃肠道	意识障碍	癫痫	发病年龄	酸中毒	神经发育障碍	血糖（mol/L）	患者诊断年龄
1	徐可等^[7]	2014	男	c.960dup	c.960dup	+	-	-	+	+	+	1岁 4个月	+	-	0.42	1岁 11个月
2	Li等^[8]	2017	女	c.960dup	c.704del	+	-	-	+	+	+	3 d	+	-	0.3	5岁 6个月
3	Li等^[8]	2017	女	c.960dup	c.825+1G>A	○	○	○	+	+	+	4岁	+	-	0.6	7岁 3个月
4	Li等^[8]	2017	男	c.720_729del	c.490G>A	○	○	○	+	-	+	1 d	+	+	0.6	10岁 8个月
5	逯静茹等^[9]	2017	女	c.960dup	c.960dup	-	+	-	+	+	+	<1岁	+	-	0.6	23岁
6	赵银霞等^[10]	2017	女	c.355G>A	c.355G>A	+	-	-	+	+	-	○	+	-	+	2岁
7	董慧等^[11]	2017	男	c.974T>A	c.755A>T	-	+	-	+	+	+	1岁 3个月	+	+	0.52	2岁 5个月
8	张赟健等^[4]	2018	男	c.704del	c.959dup	+	-	-	+	+	+	2 d	+	+	1.9	2岁 5个月
9	毋盛楠等^[12]	2019	男	c.826-2T>C	c.490G>A	-	-	-	+	-	-	3岁	+	-	0.5	3岁
10	吕楠等^[13]	2019	男	c.333+ 1_2delinsTC	c.490G>A	+	+	+	-	+	+	1岁 8个月	+	+	0.3	7岁
11	吕楠等^[13]	2019	男	c.333+ 1_2delinsTC	c.490G>A	-	+	+	-	-	+	3岁 6个月	-	-	4.5	5岁 8个月
12	Wang等^[14]	2020	男	c.333+2T>G	c.333+2T>G	+	-	-	-	-	+	7个月	+	-	+	9个月
13	孟华夏等^[15]	2020	女	c.960dup	c.500C>A	+	+	+	+	+	-	10个月	+	-	<0.3	2岁 3个月
14	杨凤华等^[16]	2020	男	c.960dup	c.960dup	+	-	-	+	+	-	3 d	+	+	1.6	2岁 6个月
15	吴冰冰^[17]	2021	男	c.704del	c.959dup	+	-	-	-	+	+	1岁 4个月	○	-	○	2岁
16	杨蒙洁等^[18]	2021	男	c.960dup	c.355G>A	+	-	-	+	+	+	6岁 3个月	+	-	2.1	13岁 5个月
17	金颖等^[19]	2022	男	c.861C>A	c.490G>A	+	-	-	+	-	-	3岁	+	-	2.67	7岁 2个月
18	金颖等^[19]	2022	女	c.861C>A	c.490G>A	+	-	-	+	+	-	1岁 5个月	+	-	1.28	1岁 8个月
19	Cao等^[20]	2022	女	c.355G>A	c.355G>A	○	○	○	+	+	+	8个月	+	-	2.0	6岁 4个月
20	Cao等^[20]	2022	男	c.490G>A	c.923C>G	-	-	+	-	+	-	1岁 6个月	+	-	1.3	2岁 6个月
21	Yi等^[21]	2022	女	c.761A>G	c.778G>A	-	-	-	-	+	+	4岁 1个月	+	-	0.48	4岁 1个月
22	古再丽阿依 ·艾萨等^[22]	2023	女	c.960dup	c.974T>A	+	-	-	+	+	-	1岁 1个月	+	-	0.2	1岁 5个月
23	Liang等^[23]	2023	男	c.962C>T	c.761A>G	○	○	○	-	+	+	3岁	+	+	0.02	12岁
24	余佳等^[24]	2024	男	c.974T>A	c.960dup	-	-	-	+	+	-	4岁	○	-	0.5	6岁 10个月
25	Xin等^[25]	2024	男	c.490G>A	c.861C>A	+	-	-	+	-	+	1岁 11个月	+	-	2.5	7岁
26	Ni等^[3]	2024	男	c.704del	c.959dup	○	○	○	+	-	-	新生儿	+	-	+	2岁
27	Ni等^[3]	2024	男	c.355G>A	c.960dup	+	-	+	+	+	+	1岁 8个月	+	○	+	2岁 6个月
28	Ni等^[3]	2024	男	c.841G>A	c.778G>A	+	-	-	+	+	+	11个月	+	-	+	1岁
29	Ni等^[3]	2024	男	c.355G>A	Exon1 deletion	-	-	-	-	-	+	新生儿	-	-	+	3岁
30	Ni等^[3]	2024	女	c.490G>A	c.490G>A	+	-	-	-	+	+	3岁	-	-	+	3岁
31	本病例	2025	女	c.778G>A	c.977T>C	+	+	-	+	+	-	2岁 1个月	+	-	3.4	3岁

序号	文献	发表年份	患者性别	变异1	变异2	发病诱因			临床表现			发病年龄	酸中毒	神经发育障碍	血糖（mol/L）	患者诊断年龄
序号	文献	发表年份	患者性别	变异1	变异2	感染	水果	空腹	胃肠道	意识障碍	癫痫	发病年龄	酸中毒	神经发育障碍	血糖（mol/L）	患者诊断年龄
1	徐可等^[7]	2014	男	c.960dup	c.960dup	+	-	-	+	+	+	1岁 4个月	+	-	0.42	1岁 11个月
2	Li等^[8]	2017	女	c.960dup	c.704del	+	-	-	+	+	+	3 d	+	-	0.3	5岁 6个月
3	Li等^[8]	2017	女	c.960dup	c.825+1G>A	○	○	○	+	+	+	4岁	+	-	0.6	7岁 3个月
4	Li等^[8]	2017	男	c.720_729del	c.490G>A	○	○	○	+	-	+	1 d	+	+	0.6	10岁 8个月
5	逯静茹等^[9]	2017	女	c.960dup	c.960dup	-	+	-	+	+	+	<1岁	+	-	0.6	23岁
6	赵银霞等^[10]	2017	女	c.355G>A	c.355G>A	+	-	-	+	+	-	○	+	-	+	2岁
7	董慧等^[11]	2017	男	c.974T>A	c.755A>T	-	+	-	+	+	+	1岁 3个月	+	+	0.52	2岁 5个月
8	张赟健等^[4]	2018	男	c.704del	c.959dup	+	-	-	+	+	+	2 d	+	+	1.9	2岁 5个月
9	毋盛楠等^[12]	2019	男	c.826-2T>C	c.490G>A	-	-	-	+	-	-	3岁	+	-	0.5	3岁
10	吕楠等^[13]	2019	男	c.333+ 1_2delinsTC	c.490G>A	+	+	+	-	+	+	1岁 8个月	+	+	0.3	7岁
11	吕楠等^[13]	2019	男	c.333+ 1_2delinsTC	c.490G>A	-	+	+	-	-	+	3岁 6个月	-	-	4.5	5岁 8个月
12	Wang等^[14]	2020	男	c.333+2T>G	c.333+2T>G	+	-	-	-	-	+	7个月	+	-	+	9个月
13	孟华夏等^[15]	2020	女	c.960dup	c.500C>A	+	+	+	+	+	-	10个月	+	-	<0.3	2岁 3个月
14	杨凤华等^[16]	2020	男	c.960dup	c.960dup	+	-	-	+	+	-	3 d	+	+	1.6	2岁 6个月
15	吴冰冰^[17]	2021	男	c.704del	c.959dup	+	-	-	-	+	+	1岁 4个月	○	-	○	2岁
16	杨蒙洁等^[18]	2021	男	c.960dup	c.355G>A	+	-	-	+	+	+	6岁 3个月	+	-	2.1	13岁 5个月
17	金颖等^[19]	2022	男	c.861C>A	c.490G>A	+	-	-	+	-	-	3岁	+	-	2.67	7岁 2个月
18	金颖等^[19]	2022	女	c.861C>A	c.490G>A	+	-	-	+	+	-	1岁 5个月	+	-	1.28	1岁 8个月
19	Cao等^[20]	2022	女	c.355G>A	c.355G>A	○	○	○	+	+	+	8个月	+	-	2.0	6岁 4个月
20	Cao等^[20]	2022	男	c.490G>A	c.923C>G	-	-	+	-	+	-	1岁 6个月	+	-	1.3	2岁 6个月
21	Yi等^[21]	2022	女	c.761A>G	c.778G>A	-	-	-	-	+	+	4岁 1个月	+	-	0.48	4岁 1个月
22	古再丽阿依 ·艾萨等^[22]	2023	女	c.960dup	c.974T>A	+	-	-	+	+	-	1岁 1个月	+	-	0.2	1岁 5个月
23	Liang等^[23]	2023	男	c.962C>T	c.761A>G	○	○	○	-	+	+	3岁	+	+	0.02	12岁
24	余佳等^[24]	2024	男	c.974T>A	c.960dup	-	-	-	+	+	-	4岁	○	-	0.5	6岁 10个月
25	Xin等^[25]	2024	男	c.490G>A	c.861C>A	+	-	-	+	-	+	1岁 11个月	+	-	2.5	7岁
26	Ni等^[3]	2024	男	c.704del	c.959dup	○	○	○	+	-	-	新生儿	+	-	+	2岁
27	Ni等^[3]	2024	男	c.355G>A	c.960dup	+	-	+	+	+	+	1岁 8个月	+	○	+	2岁 6个月
28	Ni等^[3]	2024	男	c.841G>A	c.778G>A	+	-	-	+	+	+	11个月	+	-	+	1岁
29	Ni等^[3]	2024	男	c.355G>A	Exon1 deletion	-	-	-	-	-	+	新生儿	-	-	+	3岁
30	Ni等^[3]	2024	女	c.490G>A	c.490G>A	+	-	-	-	+	+	3岁	-	-	+	3岁
31	本病例	2025	女	c.778G>A	c.977T>C	+	+	-	+	+	-	2岁 1个月	+	-	3.4	3岁

组别	基因变异	氨基酸改变	患者序号
Ⅰ	c.704del；c.959dup	p.P235Qfs42；p.S321Vfs13	8，15，26
Ⅱ	c.960dup；HOM	p.S321Vfs*13	1，5，14
Ⅲ	c.355G>A；c.960dup	p.D119N；p.S321Vfs*13	16，27
Ⅳ	c.960dup；c.974T>A	p.S321Vfs*13；p.V325E	22，24
Ⅴ	c.490G>A；c.861C>A	p.G164S；p.Y287*	17，18，25
Ⅵ	c.355G>A；HOM	p.D119N	6，19

组别	基因变异	氨基酸改变	患者序号
Ⅰ	c.704del；c.959dup	p.P235Qfs42；p.S321Vfs13	8，15，26
Ⅱ	c.960dup；HOM	p.S321Vfs*13	1，5，14
Ⅲ	c.355G>A；c.960dup	p.D119N；p.S321Vfs*13	16，27
Ⅳ	c.960dup；c.974T>A	p.S321Vfs*13；p.V325E	22，24
Ⅴ	c.490G>A；c.861C>A	p.G164S；p.Y287*	17，18，25
Ⅵ	c.355G>A；HOM	p.D119N	6，19