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20例糖原累积症Ⅸa型患者的临床和基因特点分析

李玉川 陆怡 冯佳燕 王建设

李玉川, 陆怡, 冯佳燕, 等. 20例糖原累积症Ⅸa型患者的临床和基因特点分析[J]. 临床肝胆病杂志, 2021, 37(2): 380-384. DOI: 10.3969/j.issn.1001-5256.2021.02.026
引用本文: 李玉川, 陆怡, 冯佳燕, 等. 20例糖原累积症Ⅸa型患者的临床和基因特点分析[J]. 临床肝胆病杂志, 2021, 37(2): 380-384. DOI: 10.3969/j.issn.1001-5256.2021.02.026
LI YC, LU Y, FENG JY, et al. Clinical and genetic features of patients with glycogen storage disease type Ⅸa: An analysis of 20 cases[J]. J Clin Hepatol, 2021, 37(2): 380-384. DOI: 10.3969/j.issn.1001-5256.2021.02.026
Citation: LI YC, LU Y, FENG JY, et al. Clinical and genetic features of patients with glycogen storage disease type Ⅸa: An analysis of 20 cases[J]. J Clin Hepatol, 2021, 37(2): 380-384. DOI: 10.3969/j.issn.1001-5256.2021.02.026

20例糖原累积症Ⅸa型患者的临床和基因特点分析

DOI: 10.3969/j.issn.1001-5256.2021.02.026
详细信息
    作者简介:

    李玉川(1987—),男,主治医师,主要从事儿童遗传性肝病方面的研究

    通讯作者:

    陆怡,luyi7971@163.com

  • 利益冲突声明:本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突,特此声明。
  • 作者贡献声明:李玉川负责收集数据,资料分析,撰写论文;冯佳燕负责病理报告解读,提供病理图片;王建设参与课题设计;陆怡参与课题设计,拟定写作思路,指导撰写文章并最后定稿。
  • 中图分类号: R575

Clinical and genetic features of patients with glycogen storage disease type Ⅸa: An analysis of 20 cases

  • 摘要:   目的  总结糖原累积症Ⅸa型(GSD Ⅸa)患者的临床和基因特点,加强对该病的认识。  方法  回顾性分析2015年1月—2018年12月在复旦大学附属儿科医院住院并经基因确诊的20例GSD Ⅸa型患者的临床资料,总结其临床和基因特点。  结果  20例GSD Ⅸa型患者均为男性,确诊中位年龄为2.5岁。所有患者均有肝肿大,转氨酶水平升高;生长发育迟缓5例(25.0%),空腹低血糖19例(95.0%),高乳酸血症14例(70.0%),高甘油三酯血症9例(45.0%),高胆固醇血症5例(25.0%)。8例患者进行了空腹血酮检查,结果显示均升高;所有患者尿酸均正常,5例(25.0%)患者尿酮体阳性。18例患者进行了肝穿刺检查,其中15例存在轻至中度肝纤维化。共检测到16种PHKA2基因突变,5种为已知致病突变,11种为新突变,其中c.3614位点是高发突变位点。所有患者均使用生玉米淀粉治疗,大多数患者的临床表现均为好转。  结论  GSD Ⅸa型以男性为主。肝肿大,转氨酶升高,生长发育迟缓,空腹低血糖,空腹血酮升高,尿酸正常需考虑该病可能。可通过肝穿刺协助诊断,临床生化指标和基因检测可明确诊断及分型。该病多数临床表现较轻,但也可导致肝纤维化,使用生玉米淀粉治疗能够改善病情。
  • 图  1  患者肝脏病理检查结果

    注:a,HE染色示肝细胞肿胀,肝细胞弥漫性胞浆淡染,胞膜清晰,呈“植物细胞壁”样排列(×400);b,PAS染色示糖原颗粒蓄积(×400);c,MASSON染色示汇管区纤维组织轻度增生(×400)。

    表  1  20例GSD Ⅸa型患者的临床及病理资料

    病例 确诊年龄(岁) 确诊时身高(cm)/百分位 2020年9月随访时身高(cm)/百分位 确诊时体质量(kg)/百分位 2020年9月随访时体质量(kg)/百分位 ALT (U/L) AST (U/L)
    1 2.33 85/10th 118/50th 14.5/75th 31.0/97th 170 172
    2 1.50 86/90th 118/25th 11.0/50th 21.0/25th 153 212
    3 2.00 87/25th 123/25th 14.0/75th 24.0/50th 67 114
    4 2.08 85/10th 105/10th 13.5/75th 17.0/25th 1530 3061
    5 2.00 84/10th 104/10th 13.0/50th 18.0/50th 513 554
    6 1.92 86/50th 119/75th 12.0/50th 26.0/97th 156 132
    7 3.67 85/3rd 113/25th 14.0/10th 24.0/75th 205 548
    8 8.00 127/25th 139/25th 29.0/50th 37.0/50th 61 69
    9 3.83 92/3rd 125/25th 13.0/3rd 24.0/25th 186 192
    10 5.33 100/3rd 135/25th 20.0/50th 33.0/50th 176 233
    11 3.00 104/50th 140/75th 18.0/75th 45.0/97th 69 108
    12 1.75 80/10th 103/25th 11.0/25th 17.0/50th 190 170
    13 2.50 90/10th 135/75th 13.0/50th 39.0/97th 308 164
    14 7.00 115/3rd 137/50th 18.5/3rd 28.0/25th 231 265
    15 1.25 78/25th 98/25th 12.0/90th 15.0/50th 106 109
    16 1.83 83/10th 130/75th 12.0/50th 29.0/75th 232 425
    17 2.58 91/25th 124/75th 14.5/75th 29.0/97th 108 133
    18 4.00 106/75th 136/75th 18.0/75th 31.0/75th 122 108
    19 4.92 103/3rd 135/25th 18.0/50th 32.0/50th 223 170
    20 3.75 100/25th 114/25th 16.0/50th 19.0/25th 93 101
    病例 空腹血糖(mmol/L) 空腹血酮(mmol/L) 甘油三酯(mmol/L) 总胆固醇(mmol/L) 乳酸(mmol/L) 肝纤维化分期
    1 3.4 1.4 2.61 4.67 2.5 S0
    2 2.9 0.5 1.85 2.20 1.4 S0
    3 2.8 0.84 4.49 2.8 S0
    4 3.0 0.5 2.20 6.01 8.0 S1~2
    5 3.6 1.16 4.19 3.9 S1~2
    6 2.0 2.6 0.84 2.73 2.7 S1~2
    7 3.5 1.3 1.66 4.46 7.5 S1~2
    8 3.2 1.25 5.73 3.2 S1~2
    9 3.4 1.71 6.78 4.2 S1~2
    10 2.9 1.34 4.41 1.8 S1~2
    11 3.4 1.23 4.26 1.9 S1~2
    12 4.5 0.8 1.49 4.06 3.6 S1~2
    13 2.8 1.73 3.55 2.8 S1~2
    14 2.9 1.2 2.51 5.74 2.6 S1~2
    15 3.6 1.6 2.19 4.31 1.7 S1~2
    16 3.0 1.63 4.26 1.5 S1~2
    17 2.8 1.74 5.70 3.4 S3
    18 3.4 0.71 4.89 1.5 S3
    19 2.0 1.07 3.40 2.3
    20 3.2 2.70 4.26 2.9
    注:ALT正常值9~50 U/L;AST正常值15~40 U/L;空腹血糖正常值3.9~6.1 mmol/L;空腹血酮正常值0~0.3 mmol/L;甘油三酯正常值0~1.7 mmol/L;总胆固醇正常值0~5.18 mmol/L;乳酸正常值0.5~2.2 mmol/L。
    下载: 导出CSV

    表  2  20例GSD Ⅸa型患者PHKA2基因检测结果

    病例 碱基改变 氨基酸改变 突变类型 备注
    1 c.3331C>T p.R1111X 无义突变 新突变
    2 c.883C>T p.R295C 错义突变 已报道
    3 c.347A>G p.Y116C 错义突变 新突变
    4 c.883C>T p.R295C 错义突变 已报道
    5 c.3614C>T p.P1205L 错义突变 已报道
    6 c.3614C>T p.P1205L 错义突变 已报道
    7 c.773G>A p.G258E 错义突变 新突变
    8 c.3614C>T p.P1205L 错义突变 已报道
    9 c.3614C>T p.P1205L 错义突变 已报道
    10 c.884G>A p.R295H 错义突变 已报道
    11 c.3614C>G p.P1205R 错义突变 新突变
    12 c.2597+1G>C Splicing 剪接突变 新突变
    13 c.919-2A>G Splicing 剪接突变 新突变
    14 c.395A>G p.H132R 错义突变 新突变
    15 c.285G>C p.Q95H 错义突变 新突变
    16 c.898G>A p.G300S 错义突变 新突变
    17 c.338A>G p.H113R 错义突变 已报道
    18 c.3210_3212delGAG p.R1070del 缺失突变 已报道
    19 c.524_537+1del15 FS+Splicing 小片段缺失 新突变
    20 c.3336+2T>C Splicing 剪接突变 新突变
    下载: 导出CSV
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  • 收稿日期:  2020-08-01
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