Glutaric acidemia type I (GA1) is caused by severe deficiency of glutaryl‐CoA dehydrogenase activity, resulting in an accumulation of glutaric acid and glutarylcarnitine (C5DC) in the organism. Patients affected by GA1 are asymptomatic in the neonate period but usually manifest chronically progressive neurodegeneration apart from severe encephalopathic crises associated with acute striatum necrosis. Neurological manifestations like dyskinesia, dystonia, hypotonia, muscle stiffness, and spasticity are present. Treatment is based on protein/lysine restriction and l‐carnitine supplementation. In this work, we evaluated markers of neurodegeneration and inflammation, namely BDNF (brain‐derived neurotrophic factor), NCAM (neuronal adhesion molecule), PDGF‐AA (platelet‐derived growth factor), and cathepsin‐d in plasma of six treated GA1 patients. We first found marked increases of plasma C5DC concentrations in GA1 patients, as well as increased levels of the markers BDNF and cathepsin‐d as compared to those of age‐matched healthy children. Furthermore, C5DC concentrations were highly correlated with the levels of cathepsin‐d. These results may demonstrate that brain tissue degeneration is present in GA1 patients and that there is a relationship between increased metabolites concentrations with this process. To the best of our knowledge, this is so far the first study showing altered peripheral parameters of neurodegeneration and inflammation in GA1 patients.

中文翻译：

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I型戊二酸血症患者血浆中BDNF和组织蛋白酶D水平升高可能是神经变性的外周标志物

戊二酸血症 I 型 (GA1) 是由戊二酰辅酶 A 脱氢酶活性严重缺乏引起的，导致机体中戊二酸和戊二酰肉碱 (C5DC) 的积累。受 GA1 影响的患者在新生儿期无症状，但除了与急性纹状体坏死相关的严重脑病危象外，通常表现出慢性进行性神经变性。存在运动障碍、肌张力障碍、张力减退、肌肉僵硬和痉挛等神经系统表现。治疗基于蛋白质/赖氨酸限制和左旋肉碱补充剂。在这项工作中，我们评估了神经变性和炎症的标志物，即 BDNF（脑源性神经营养因子）、NCAM（神经元粘附分子）、PDGF-AA（血小板源性生长因子）和 6 种处理过的 GA1 血浆中的组织蛋白酶-d耐心。我们首先发现与年龄匹配的健康儿童相比，GA1 患者血浆 C5DC 浓度显着增加，以及标志物 BDNF 和组织蛋白酶-d 的水平增加。此外，C5DC 浓度与组织蛋白酶-d 的水平高度相关。这些结果可能表明 GA1 患者存在脑组织变性，并且代谢物浓度增加与该过程之间存在关系。据我们所知，这是迄今为止第一项显示 GA1 患者神经变性和炎症的外周参数改变的研究。C5DC 浓度与组织蛋白酶-d 的水平高度相关。这些结果可能表明 GA1 患者存在脑组织变性，并且代谢物浓度增加与该过程之间存在关系。据我们所知，这是迄今为止第一项显示 GA1 患者神经变性和炎症的外周参数改变的研究。C5DC 浓度与组织蛋白酶-d 的水平高度相关。这些结果可能表明 GA1 患者存在脑组织变性，并且代谢物浓度增加与此过程之间存在关系。据我们所知，这是迄今为止第一项显示 GA1 患者神经变性和炎症的外周参数改变的研究。