Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, No. 101 Lu Yuan Dong Road, Tong-Zhou District, Beijing, 101100, China.
Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, 101100, China.
Orphanet J Rare Dis. 2022 Feb 21;17(1):62. doi: 10.1186/s13023-022-02233-9.
Current world experience regarding living donor liver transplantation (LDLT) in the treatment of propionic acidemia (PA) is limited, especially in terms of using obligate heterozygous carriers as donors. This study aimed to evaluate the clinical outcomes of LDLT in children with PA.
From November 2017 to January 2020, 7 of the 192 children who underwent LDLT at our institution had been diagnosed with PA (median age, 2.1 years; range, 1.1-5.8 years). The primary indication for transplantation was frequent metabolic decompensations in 6 patients and preventative treatment in 1 patient. Of the seven parental living donors, six were genetically proven obligate heterozygous carriers.
During a median follow-up of 23.9 months (range, 13.9-40.2 months), all patients were alive with 100% allograft survival, and no severe transplant-related complications occurred. In the case of liberalized protein intake, they did not suffer metabolic decompensation or disease-related complications and made progress in neurodevelopmental delay and body growth, as well as blood and urinary metabolite levels. In one patient with pre-existing mild dilated cardiomyopathy, her echocardiogram results completely normalized 13.8 months post-transplant. All living donors recovered well after surgery, with no metabolic decompensations or procedure-related complications. Western blotting revealed that the hepatic expressions of PCCA and PCCB in one of the heterozygous donors were comparable to those of the normal healthy control at the protein level.
LDLT using partial liver grafts from asymptomatic obligate heterozygous carrier donors is a viable therapeutic option for selected PA patients, with no negative impact on donors' and recipients' clinical courses.
目前，关于丙酸血症（PA）治疗中活体肝移植（LDLT）的全球经验有限，尤其是在使用必需杂合子携带者作为供体方面。本研究旨在评估 LDLT 在 PA 患儿中的临床结局。
2017 年 11 月至 2020 年 1 月，我院 192 例行 LDLT 的患儿中，有 7 例诊断为 PA（中位年龄 2.1 岁，范围 1.1-5.8 岁）。移植的主要指征是 6 例患儿频繁出现代谢失代偿，1 例患儿预防性治疗。7 名父母供体中，6 名经基因证实为必需杂合子携带者。
中位随访 23.9 个月（范围 13.9-40.2 个月）期间，所有患儿均存活，移植物存活率为 100%，无严重移植相关并发症。在放宽蛋白质摄入的情况下，患儿未出现代谢失代偿或疾病相关并发症，神经发育迟缓和身体生长、血液和尿液代谢物水平均有所改善。1 例存在轻度扩张型心肌病的患儿，移植后 13.8 个月其超声心动图结果完全正常。所有供体术后恢复良好，无代谢失代偿或手术相关并发症。Western blot 分析显示，1 名杂合子供体的 PCCA 和 PCCB 肝组织表达在蛋白质水平与正常健康对照相似。
使用无症状必需杂合子携带者供体的部分肝移植是治疗选择的 PA 患儿的可行治疗选择，对供体和受体的临床病程无负面影响。
