INTRODUCTION ECHS1 encodes for short-chain enoyl-CoA hydratase, a key component in b-oxidation. This enzyme is also involved in the isoleucine and valine catabolic pathways. The literature contains reports of scattered cases of ECHS1 mutation, which show a wide clinical spectrum of presentation. Despite that the clinical spectrum of the disease has not been defined so far due to the absence of previous systematic reviews and descriptions of large series of patients. METHODS We performed a systematic literature review of so far reported ECHS1 mutated patients and we reported two additional cases. We pointed out clinical and neuroradiological features of all patients. RESULTS 45 patients were included in the analysis. Based on clinical and neuroradiological feature we were able to distinguish four main phenotypes of ECHS1deficiency: a severe neonatal presentation with a rapid and fatal course and significant white matter abnormalities; a severe infantile variant with slower neurological deterioration, developmental delay, pyramidal and extrapyramidal signs, optic atrophy, feeding difficulties, and degeneration of the deep gray nuclei; a slowly progressive infantile form, qualitatively similar to the previous phenotype, but less severe with mainly basal ganglia involvement; and a final phenotype, present in only few cases, characterized by paroxysmal exercise-induced dystonic attacks, normal neurological examination between these episodes, and isolated pallidal degeneration on MRI. INTERPRETATION ECHS1 mutations cause metabolic encephalopathy with a wide range of clinical presentations that can be grouped into four main phenotypes, each with a distinct profile in terms of severity on clinical presentation, disease course and MRI involvement.

中文翻译：

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短链烯酰-Coa 水解酶-1 (ECHS1) 缺乏症的表型谱

简介 ECHS1 编码短链烯酰辅酶A 水合酶，这是β-氧化的关键成分。该酶还参与异亮氨酸和缬氨酸分解代谢途径。文献报道了 ECHS1 突变的分散病例，这些病例显示出广泛的临床表现。尽管由于先前缺乏对大量患者的系统评价和描述，该疾病的临床谱迄今尚未确定。方法我们对迄今为止报道的 ECHS1 突变患者进行了系统的文献回顾，并报告了另外两个病例。我们指出了所有患者的临床和神经放射学特征。结果 45 名患者被纳入分析。基于临床和神经放射学特征，我们能够区分 ECHS1 缺陷的四种主要表型：严重的新生儿表现，具有快速且致命的病程和显着的白质异常；严重的婴儿型变异，具有较慢的神经功能恶化、发育迟缓、锥体和锥体外系体征、视神经萎缩、喂养困难和深灰色细胞核退化；一种缓慢进展的婴儿型，在性质上与以前的表型相似，但不那么严重，主要是基底神经节受累；最后的表型仅出现在少数病例中，其特征是阵发性运动诱发的肌张力障碍发作，这些发作之间的神经系统检查正常，以及 MRI 上孤立的苍白球变性。解释 ECHS1 突变导致代谢性脑病具有广泛的临床表现，可分为四种主要表型，