Niemi Anna-Kaisa, Kim Irene K, Krueger Casey E, Cowan Tina M, Baugh Nancy, Farrell Rachel, Bonham Clark A, Concepcion Waldo, Esquivel Carlos O, Enns Gregory M
Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA.
Division of Abdominal Transplantation, Department of Surgery, Stanford University, Stanford, CA.
J Pediatr. 2015 Jun;166(6):1455-61.e1. doi: 10.1016/j.jpeds.2015.01.051. Epub 2015 Mar 11.
To assess biochemical, surgical, and long-term outcomes of liver (LT) or liver-kidney transplantation (LKT) for severe, early-onset methylmalonic acidemia/acid (MMA).
A retrospective chart review (December 1997 to May 2012) of patients with MMA who underwent LT or LKT at Lucile Packard Children's Hospital at Stanford.
Fourteen patients underwent LT (n = 6) or LKT (n = 8) at mean age 8.2 years (range 0.8-20.7). Eleven (79%) were diagnosed during the neonatal period, including 6 by newborn screening. All underwent deceased donor transplantation; 12 (86%) received a whole liver graft. Postoperative survival was 100%. At a mean follow-up of 3.25 ± 4.2 years, patient survival was 100%, liver allograft survival 93%, and kidney allograft survival 100%. One patient underwent liver re-transplantation because of hepatic artery thrombosis. After transplantation, there were no episodes of hyperammonemia, acidosis, or metabolic decompensation. The mean serum MMA at the time of transplantation was 1648 ± 1492 μmol/L (normal <0.3, range 99-4420). By 3 days, post-transplantation levels fell on average by 87% (mean 210 ± 154 μmol/L), and at 4 months, they were 83% below pre-transplantation levels (mean 305 ± 108 μmol/L). Developmental delay was present in 12 patients (86%) before transplantation. All patients maintained neurodevelopmental abilities or exhibited improvements in motor skills, learning abilities, and social functioning.
LT or LKT for MMA eradicates episodes of hyperammonemia, results in excellent long-term survival, and suggests stabilization of neurocognitive development. Long-term follow-up is underway to evaluate whether patients who undergo early LT need kidney transplantation later in life.
评估肝移植（LT）或肝肾联合移植（LKT）治疗重度早发型甲基丙二酸血症/酸（MMA）的生化、手术及长期预后。
对1997年12月至2012年5月在斯坦福大学露西尔·帕卡德儿童医院接受LT或LKT的MMA患者进行回顾性病历审查。
14例患者接受了LT（n = 6）或LKT（n = 8），平均年龄8.2岁（范围0.8 - 20.7岁）。11例（79%）在新生儿期被诊断，其中6例通过新生儿筛查确诊。所有患者均接受了尸体供体移植；12例（86%）接受了全肝移植。术后生存率为100%。平均随访3.25 ± 4.2年，患者生存率为100%，肝移植存活率为93%，肾移植存活率为100%。1例患者因肝动脉血栓形成接受了再次肝移植。移植后，未发生高氨血症、酸中毒或代谢失代偿事件。移植时血清MMA平均水平为1648 ± 1492 μmol/L（正常<0.3，范围99 - 4420）。移植后3天，水平平均下降87%（平均210 ± 154 μmol/L），4个月时，比移植前水平低83%（平均305 ± 108 μmol/L）。12例患者（86%）移植前存在发育迟缓。所有患者均保持神经发育能力或在运动技能、学习能力和社交功能方面有所改善。
MMA的LT或LKT可消除高氨血症发作，带来优异的长期生存率，并表明神经认知发育趋于稳定。正在进行长期随访，以评估早期接受LT的患者日后是否需要肾移植。
