Methylmalonic and propionic aciduria
Methylmalonic and propionic aciduria
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DOI：
10.1002/ajmg.c.30090
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发表时间：
2006-05-15
影响因子：
3.1
通讯作者：
Dionisi-Vici, C
中科院分区：
文献类型：
--
作者：
Deodato, F;Boenzi, S;Dionisi-Vici, C
甲基丙二酸尿和丙酸尿是支链有机酸尿最常见的形式。这些常染色体隐性遗传病分别由甲基丙二酰辅酶a变化酶和丙二酰辅酶a羧化酶活性不足引起。临床上，急性或慢性神经系统症状是由代谢阻滞近端有毒化合物的积累引起的。表型从新生儿发病时死亡率高、预后差的严重形式到发病较晚的轻度形式不等。在这两种情况下，临床过程主要是危及生命的代谢失代偿发作和严重器官衰竭复发的风险。尽管治疗有所改善，但总体结果仍然令人失望，两种疾病之间没有重大差异。诊断是基于体液中存在的特征化合物，如通过尿液中的有机酸分析和血液中的酰基肉碱谱检测到的。治疗是基于低蛋白高能量饮食，补充肉碱和甲硝唑。一些甲基丙二酸尿症（MMA）患者对维生素B12药理学剂量有反应。鉴于长期预后不良，肝移植最近被尝试作为常规药物治疗的替代疗法来治疗潜在的代谢缺陷。然而，迄今为止的总体经验并没有清楚地表明它在防止进一步恶化或改善生存和生活质量方面的有效性。最近实施的电喷雾串联质谱新生儿筛查降低了早期死亡率，改善了短期结果，与临床检测病例相比，筛查人群中两种疾病的检出率没有改变。然而，由于患者数量有限，随访时间短，尚不能得出其对甲基丙二酸和丙酸血症长期预后影响的最终结论。(c) 2006 Wiley-Liss, Inc。
Methylmalonic and propionic aciduria (PA) are the most frequent forms of branched-chain organic acidurias. These autosomal recessive disorders result from deficient activity of methylmalonyl-CoA mutase and propionyl-CoA carboxylase, respectively. Clinically, acute or chronic neurologic signs are caused by the accumulation of toxic compounds proximal to the metabolic block. Phenotype varies from severe neonatal-onset forms with high mortality and poor outcome to milder forms with a later onset. In both cases the clinical course is dominated by the risk of relapses of life-threatening episodes of metabolic decompensation and of severe organ failure. Despite improvement of treatment, the overall outcome remains disappointing with no major differences between the two diseases, The diagnosis is based on the presence of characteristic compounds in body fluids as detected by organic acid analysis in urine and acylcarnitine profile in blood. Therapy is based on low-protein high-energy diet, carnitine supplementation, and metronidazole. Some patients with methylmalonic aciduria (MMA) respond to pharmacological doses of vitamin B12. Given the poor long-term prognosis, liver transplantation has been recently attempted as an alternative therapy to conventional medical treatment to cure the underlying metabolic defect. Nevertheless, the overall experience to date does not clearly demonstrate its effectiveness in preventing further deterioration or improving survival and quality of life. The recent implementation of neonatal screening by electrospray tandem mass spectrometry has decreased early mortality and improved the short-term outcome, without changing the detection rate of both diseases in the screening population compared to clinically detected cases. However, the limited number of patients and the short duration of their follow-up do not yet permit drawing final conclusions on its effect on the long-term outcome of methylmalonic and propionic acidemia. (c) 2006 Wiley-Liss, Inc.