Heterozygous living donor liver transplantation for pediatric maple syrup urine disease with new compound mutation of BCKDHB gene: a case report and literature review
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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。 -
关键词:
- 枫糖尿病 /
- 活体器官捐献 /
- 杂合子 /
- 肝移植 /
- 支链α-酮酸脱氢酶(BCKDH) /
- 支链氨基酸(BCAA) /
- 基因突变 /
- 急性代谢事件
Abstract:Objective To evaluate the clinical efficacy of heterozygous living donor liver transplantation for pediatric maple syrup urine disease. Methods A 3-year-old boy was admitted to the hospital on July 5, 2017 due to maple syrup urine disease for half a year. The child presented with paroxysmal dysarthria and motor dysfunction of the lower limbs under fasting status for half a year, accompanied with obvious maple syrup urine odor and slow language development. No other growth abnormality or mental defects were observed. Serum branched chain amino acid (BCAA) assay detected that the level of leucine was 684 μmol/L and 559 μmol/L for the valine. The child was diagnosed with maple syrup urine disease type b based on gene detection combined with BCAA assay. Living donor liver transplantation from his biological father was performed. Postoperatively, routine immunosuppression, anti-virus, anti-infection therapies, maintenance of fluid, electrolyte, and acid-base balance and other necessary nutritional support were given. The dose of tacrolimus was adjusted according to biochemical parameters and cytochrome P450(CYP)3A5 genotype of the recipient. Glucocorticoid administration was terminated at approximately 6 months after operation. Results The liver function of the recipient was recovered to normal range at postoperative 1 month, and basically stabilized at 3 years after surgery. The amino acid level was decreased to normal level immediately after operation, and BCAA was continually declined after normal diet for postoperative 1 month. As of the submission date, the recipient grew well in a stable condition and achieved high quality of life. Conclusions Heterozygous living donor liver transplantation is a safe and effective treatment of maple syrup urine disease, which reduces the possibility of sudden acute metabolic events, significantly improves the quality of life of the recipient and provides a novel idea for surgical treatment of maple syrup urine disease. -
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 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 -① 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/L② 注:①-为无数据。
②该中心亮氨酸正常值范围为51~170 μmol/L。 -
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