有机酸血症,尤其是丙酸血症(PA)和甲基丙二酸血症(MMA),可能在生命的最初几个小时到几天内出现临床症状。新生儿时期的经典表现包括代谢性酸中毒,高乳酸血症,和不受限制的蛋白质摄入导致的高氨血症。实施新生儿筛查以诊断和开始早期治疗有助于降低新生儿死亡率和提高生存率。尽管早期诊断和适当的管理,这些患者容易反复出现代谢性酸中毒和高氨血症,导致频繁住院.肝移植(LT)已被提出作为一种治疗方式,以减少不受医疗管理控制的代谢代偿。关于LT结果的公开报告显示了移植后临床和生化特征的异质性结果。因此,我们评估了本机构LT的结局,并将其与之前发表的数据进行了比较.
我们对9名接受LT的PA或MMA患者和2名接受LT和肾移植(KT)的MMA患者进行了回顾性图表回顾。数据包括住院次数,实验室措施,心脏和神经系统的结果,膳食蛋白质摄入量,并收集生长参数。
MMA患者移植的中位年龄为7.2岁,中位随访时间为4.3年。PA患者的中位移植年龄为1.9岁,中位随访时间为5.4年。术后1年和5年生存率为100%。我们的大多数受试者在LT后没有任何高氨血症或胰腺炎发作。LT后血浆甘氨酸显著减少。一名受试者在不受限制的蛋白质饮食中,LT后氨轻度升高,这表明即使在LT后也可能需要限制蛋白质。
在MMA和PA中LT的大型单中心研究中,我们表明LT可以降低代谢失代偿的发生率。此外,我们的数据提示,LT可能与PA和MMA患者住院次数减少和线性生长改善相关.
Organic acidemias, especially propionic acidemia (PA) and methylmalonic acidemia (MMA), may manifest clinically within the first few hours to days of life. The classic presentation in the newborn period includes metabolic acidosis, hyperlactatemia, and hyperammonemia that is precipitated by unrestricted protein intake. Implementation of newborn screening to diagnose and initiate early treatment has facilitated a reduction in neonatal mortality and improved survival. Despite early diagnosis and appropriate management, these individuals are prone to have recurrent episodes of metabolic acidosis and hyperammonemia resulting in frequent hospitalizations. Liver transplantation (LT) has been proposed as a treatment modality to reduce metabolic decompensations which are not controlled by medical management. Published reports on the outcome of LT show heterogeneous results regarding clinical and biochemical features in the post transplantation period. As a result, we evaluated the outcomes of LT in our institution and compared it to the previously published data.
We performed a retrospective chart
review of nine individuals with PA or MMA who underwent LT and two individuals with MMA who underwent LT and kidney transplantation (KT). Data including number of hospitalizations, laboratory measures, cardiac and neurological outcomes, dietary protein intake, and growth parameters were collected.
The median age of transplantation for subjects with MMA was 7.2 years with a median follow up of 4.3 years. The median age of transplantation for subjects with PA was 1.9 years with a median follow up of 5.4 years. The survival rate at 1 year and 5 years post-LT was 100%. Most of our subjects did not have any episodes of hyperammonemia or pancreatitis post-LT. There was significant reduction in plasma glycine post-LT. One subject developed mild elevation in ammonia post-LT on an unrestricted protein diet, suggesting that protein restriction may be indicated even after LT.
In a large single center study of LT in MMA and PA, we show that LT may reduce the incidence of metabolic decompensation. Moreover, our data suggest that LT may be associated with reduced number of hospitalizations and improved linear growth in individuals with PA and MMA.