Liver transplantation is not curative for methylmalonic acidopathy caused by methylmalonyl-CoA mutase deficiency
- 作者：Paige Kaplan ; Can Ficicioglu ; Alice T. Mazur ; Michael J. Palmieri and Gerard T. Berry
- 关键词：Methylmalonic acid ; Methylmalonic acidemia ; Methylmalonic acidopathy ; Methylmalonyl-CoA mutase deficiency ; Liver transplantation ; Metabolic stroke
- 刊名：Molecular Genetics and Metabolism
- 出版年：2006
- 期刊代码：175_10967192
- 类别：bio
- 出版时间：August 2006
- 卷：88
- 期：4
- 页码：322-326
- 文件大小：170 K
摘要
Methylmalonic acidopathy resulting from severe methylmalonyl-CoA mutase deficiency causes acute, potentially lethal ketoacidotic episodes, renal failure, and acute and chronic neurologic disease. As dietary and alkali therapy is suboptimal, liver transplantation during infancy has been touted as a potential cure. However, reports in liver transplant recipients about new onset neurologic disease, in the absence of ketoacidosis, and progressive renal insufficiency have cast doubt about its effectiveness. We report the long-term (9 years) outcome for the first patient with severe methylmalonic acidopathy transplanted in the USA and provide new biochemical data that indicate why transplanted patients are still susceptible to “metabolic strokes”. In our 10-year-old male patient, there is clear evidence that the de novo synthesis of propionyl-CoA within the CNS leads to brain methylmalonate (MMA) accumulation that is largely unaffected by transplantation. Liver replacement is not a cure for methylmalonic acidopathy.