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杂合子亲属活体肝移植治疗儿童BCKDHB基因新复合突变枫糖尿病1例并文献复习

吴越 顾广祥 夏强

吴越, 顾广祥, 夏强. 杂合子亲属活体肝移植治疗儿童BCKDHB基因新复合突变枫糖尿病1例并文献复习[J]. 器官移植, 2021, 12(5): 588-594. doi: 10.3969/j.issn.1674-7445.2021.05.013
引用本文: 吴越, 顾广祥, 夏强. 杂合子亲属活体肝移植治疗儿童BCKDHB基因新复合突变枫糖尿病1例并文献复习[J]. 器官移植, 2021, 12(5): 588-594. doi: 10.3969/j.issn.1674-7445.2021.05.013
Wu Yue, Gu Guangxiang, Xia Qiang. Heterozygous living donor liver transplantation for pediatric maple syrup urine disease with new compound mutation of BCKDHB gene: a case report and literature review[J]. ORGAN TRANSPLANTATION, 2021, 12(5): 588-594. doi: 10.3969/j.issn.1674-7445.2021.05.013
Citation: Wu Yue, Gu Guangxiang, Xia Qiang. Heterozygous living donor liver transplantation for pediatric maple syrup urine disease with new compound mutation of BCKDHB gene: a case report and literature review[J]. ORGAN TRANSPLANTATION, 2021, 12(5): 588-594. doi: 10.3969/j.issn.1674-7445.2021.05.013

杂合子亲属活体肝移植治疗儿童BCKDHB基因新复合突变枫糖尿病1例并文献复习

doi: 10.3969/j.issn.1674-7445.2021.05.013
基金项目: 

国家自然科学基金青年科学基金项目 81700570

详细信息
    作者简介:

    吴越,女,1999年生,本科,Email:wuyue990124@163.com

    通讯作者:

    顾广祥,男,1985年生,博士,主治医师,研究方向为儿童肝移植, E-mail: guguangxiang@163.com

    夏强,男,1966年生,博士,教授、主任医师、博士研究生导师,研究方向为肝脏外科、肝移植临床与基础研究, E-mail: xiaqiang@medmail.com

  • 中图分类号: R617, R587.1, Q343.1+3

Heterozygous living donor liver transplantation for pediatric maple syrup urine disease with new compound mutation of BCKDHB gene: a case report and literature review

More Information
  • 摘要:   目的  总结枫糖尿病的杂合子亲属活体肝移植治疗效果。  方法  1例男性3岁患儿,因发现枫糖尿病半年于2017年7月5日入院。患儿空腹状态出现阵发性口齿不清、下肢运动功能障碍半年,枫糖样体味明显,语言发育稍迟缓,无其他生长发育异常和智力缺陷。血清支链氨基酸(BCAA)检查示亮氨酸684 μmol/L,缬氨酸559 μmol/L,经基因检测结合BCAA检查诊断为枫糖尿病Ⅰb型。行亲属活体肝移植,供者为患儿父亲。术后常规应用免疫抑制、抗病毒、抗感染方案及维持水、电解质、酸碱平衡等必要营养支持。他克莫司剂量根据生化指标和受者细胞色素P450(CYP)3A5基因型进行调整。糖皮质激素于术后6个月左右停用。  结果  受者肝功能于术后1个月恢复至正常范围,术后3年基本趋于稳定。受者氨基酸水平术后即降至正常,术后正常饮食1个月BCAA继续降低。截止至投稿日,受者生长发育良好,情况稳定,生活质量高。  结论  突变杂合子亲属活体肝移植治疗枫糖尿病安全有效,降低了突发急性代谢事件的可能性,极大地改善了受者的生活质量,为枫糖尿病的外科治疗提供了新思路。

     

  • 图  1  受者肝移植术后肝功能及他克莫司剂量变化情况

    Figure  1.  Changes of liver function and tacrolimus dose in the recipient after liver transplantation

    表  1  患儿基因测序检验结果

    Table  1.   Gene sequencing test results of the child

    基因 染色体坐标 核苷酸改变 基因亚区 纯合/杂合 氨基酸改变 致病性分析 突变来源
    BCKDHB Chr6:80837336 c.269C > T CDS2 杂合 p.T901 疑似致病 父源
    Chr6:80878616 c.502C > T CDS5 杂合 p.R168C 致病 母源
    下载: 导出CSV

    表  2  枫糖尿病病人肝移植治疗效果及预后

    Table  2.   Effect and prognosis of liver transplantation in patients with maple syrup urine disease

    研究者 年份 供者来源 例数(n) 受者年龄(岁) 随访时间(月) 存活情况 术后饮食 BCAA水平
    Wendel, et al[12] 1999 尸体器官捐献 2 2.0, 8.0 - 存活 不限制 正常值的两倍正常
    Khanna, et al[13] 2006 尸体器官捐献-多米诺 1 25 7 存活 不限制 正常范围上限
    Mazariegos, etal[14] 2008 尸体器官捐献-多米诺 5 20.4(9.0~31.0) 13.6(0.5~42.3) 存活 不限制 正常
    Gopasetty, et al[15] 2010 尸体器官捐献-多米诺 5 - 14.6(2.7~25.8) 存活 不限制 正常
    Badell, et al[16] 2013 尸体器官捐献-多米诺 1 24 30 存活 不限制 正常
    Kadohisa, et al[17] 2015 亲属活体器官捐献 1 0.8 6 存活 蛋白质摄入总量限制 正常
    Mohan, et al[18] 2016 亲属活体器官捐献 2 1.8, 3.2 72 存活 不限制 正常
    Feier, et al[19] 2016 亲属活体器官捐献 4 3.8(2.7~5.2) 19.5(11.5~37.0) 存活 不限制 正常
    Roilides, et al[20] 2016 亲属活体器官捐献 1 5 12 存活 不限制 正常至轻度升高
    Yasui, et al[21] 2016 亲属活体器官捐献 1 0.6 7.5 存活 不限制 正常至轻度升高
    蒋超, 等[22] 2016 尸体器官捐献 1 1.6 - 存活 - -
    Takano, et al[[23] 2017 亲属活体器官捐献 1 1 12 存活 不限制 正常
    Pal, et al[24] 2018 亲属活体器官捐献 1 1 24 存活 不限制 正常
    Baştürk, et al[25] 2018 亲属活体器官捐献 2 1.0, 2.5 24 存活 不限制 正常
    Celik, et al[26] 2019 尸体器官捐献-多米诺 17 17.6(4.8~32.1) 76.8(14.4~154.8) 存活 不限制 正常
    Herden, et al[27] 2019 尸体器官捐献-多米诺 15 10.9(0.3~26.1) 23.0(2.0~31.0) 存活 不限制 正常
    Roda, et al[28] 2019 亲属活体器官捐献 11 3.2(0.7~8.0) 8.0(2.0~60.0) 存活 不限制 正常
    Porta, et al[29] 2019 - 2 2.3, 3.0 0.5, 2.0 存活 不限制 亮氨酸分别为278 μmol/L和64 μmol/L
    注:①-为无数据。
    ②该中心亮氨酸正常值范围为51~170 μmol/L。
    下载: 导出CSV
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  • 收稿日期:  2021-04-23
  • 网络出版日期:  2021-09-15
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