Schlenzig J S, Poggi-Travert F, Laurent J, Rabier D, Jan D, Wendel U, Sewell A C, Revillon Y, Kamoun P, Saudubray J M
Department of Pediatrics, Hôpital Necker Enfants Malades, Paris, France.
J Inherit Metab Dis. 1995;18(4):448-61. doi: 10.1007/BF00710056.
Orthotopic liver transplantation (OLT) was performed in two patients with propionic acidaemia, a 7-year-old boy and a 9-year-old girl, diagnosed with a severe neonatal form with high risk of metabolic decompensation. In both cases the metabolic liver functions recovered within the 12 postoperative hours; no clinical symptoms of propionic acid toxicity, metabolic acidosis, severe hyperammonaemia, hyperglycinaemia or haematological abnormalities were observed. In both cases insulin-dependent diabetes mellitus occurred early after OLT (persisting in the boy's case). Severe post-transplantation complications were observed (acute rejection and CMV infection in both patients) which did not trigger metabolic decompensation. The boy developed chronic rejection and vanishing bile duct syndrome due to incomplete hepatic arterial thrombosis. He required permanent in-patient care with chronic hyperammonaemia and neurological sequelae involving the basal ganglia and died 15 months after OLT. The girl left hospital after 2 months and is presently leading a normal life with almost no dietary protein restriction (40 g protein per day). Urinary urea excretion and daily protein intake increased after liver transplantation. Propionyl- and tiglylglycine disappeared immediately after OLT. Urinary methylcitrate and 3-hydroxypropionate remained at concentrations corresponding to those before OLT. However, the total of all characteristic metabolites of organic acid analysis was reduced to 50-60% of the values before OLT in both patients. Propionylcarnitine was still detected at significant concentrations. Plasma odd-chain fatty acid concentrations decreased continuously after OLT only in the girl's case. Tissue of both transplanted livers showed increased odd-chain fatty acid concentrations 9 and 15 months after OLT, respectively, in both patients. We consider that at present OLT should only be performed in severe forms of propionic acidaemia.
对两名患有丙酸血症的患者进行了原位肝移植，一名7岁男孩和一名9岁女孩，他们被诊断为严重的新生儿型，有代谢失代偿的高风险。在这两例中，代谢性肝功能在术后12小时内恢复；未观察到丙酸毒性、代谢性酸中毒、严重高氨血症、高甘氨酸血症或血液学异常的临床症状。在这两例中，肝移植术后早期均出现胰岛素依赖型糖尿病（男孩的病例中持续存在）。观察到严重的移植后并发症（两名患者均有急性排斥反应和巨细胞病毒感染），但未引发代谢失代偿。男孩因肝动脉血栓形成不完全而发展为慢性排斥反应和胆管消失综合征。他需要长期住院治疗，伴有慢性高氨血症和累及基底神经节的神经后遗症，并在肝移植后15个月死亡。女孩在2个月后出院，目前过着正常生活，几乎没有饮食蛋白质限制（每天40克蛋白质）。肝移植后尿尿素排泄和每日蛋白质摄入量增加。丙酸和巴豆酰甘氨酸在肝移植后立即消失。尿中甲基柠檬酸和3-羟基丙酸的浓度仍与肝移植前相当。然而，两名患者有机酸分析的所有特征性代谢物总量均降至肝移植前值的50-60%。仍能检测到显著浓度的丙酰肉碱。仅在女孩的病例中，肝移植后血浆奇数链脂肪酸浓度持续下降。两名患者移植肝脏的组织在肝移植后9个月和15个月分别显示奇数链脂肪酸浓度增加。我们认为，目前原位肝移植仅应在严重形式的丙酸血症中进行。
