Laemmle Alexander, Balmer Christian, Doell Carsten, Sass Jörn Oliver, Häberle Johannes, Baumgartner Matthias R
Division of Metabolic Diseases, University Children`s Hospital, Zurich, Switzerland,
Eur J Pediatr. 2014 Jul;173(7):971-4. doi: 10.1007/s00431-014-2359-6. Epub 2014 Jun 11.
Propionic acidemia (PA) is a rare autosomal recessive organic aciduria resulting from defects in propionyl-CoA-carboxylase (PCC), a key enzyme of intermediate energy metabolism. PA mostly manifests during the neonatal period, when affected newborns develop severe metabolic acidosis and hyperammonemia. We present a previously healthy teenager, who suffered from acute fatigue and breathlessness. The patient was tachycardic, displayed a precordial heave and a systolic murmur. Cardiac investigations revealed severe dilated cardiomyopathy (DCM). Biochemical work up led to the diagnosis of PA. Remarkably, this patient of consanguineous Hispanic origin was in a good general health condition before the acute onset of DCM. Diagnosis of PA was confirmed by enzymatic and molecular genetic analysis, the latter revealing a novel homozygous mutation in the PCCB gene (c.1229G > A; p.R410Q). Residual PCC enzyme activity of approximately 14 % of normal was detected in patient's lymphocytes and fibroblasts, thereby providing a possible explanation for the hitherto asymptomatic phenotype.
Isolated DCM, although rare, can be the leading and/or sole symptom of late-onset PA. Therefore, patients with DCM should receive a comprehensive diagnostic evaluation including selective screening for inborn errors of metabolism.
丙酸血症（PA）是一种罕见的常染色体隐性有机酸尿症，由丙酰辅酶A羧化酶（PCC）缺陷引起，PCC是中间能量代谢的关键酶。PA大多在新生儿期表现出来，患病新生儿会出现严重的代谢性酸中毒和高氨血症。我们报告一名既往健康的青少年，他出现急性疲劳和呼吸困难。该患者心动过速，有胸前区隆起和收缩期杂音。心脏检查显示严重扩张型心肌病（DCM）。生化检查确诊为PA。值得注意的是，这名有西班牙裔近亲血统的患者在DCM急性发作前总体健康状况良好。通过酶学和分子遗传学分析确诊为PA，后者在PCCB基因中发现一个新的纯合突变（c.1229G＞A；p.R410Q）。在患者的淋巴细胞和成纤维细胞中检测到约为正常水平14%的残余PCC酶活性，从而为迄今无症状的表型提供了一种可能的解释。
孤立性DCM虽然罕见，但可能是迟发性PA的主要和/或唯一症状。因此，DCM患者应接受全面的诊断评估，包括对先天性代谢缺陷进行选择性筛查。
