Pediatric Research and Metabolism Unit, Reina Sofia University Hospital, University of Córdoba, 14010, Córdoba, Spain.
Maimónides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain.
Orphanet J Rare Dis. 2022 Sep 5;17(1):340. doi: 10.1186/s13023-022-02468-6.
Enoyl-CoA hydratase short-chain 1 (ECHS1) is a key mitochondrial enzyme that is involved in valine catabolism and fatty acid beta-oxidation. Mutations in the ECHS1 gene lead to enzymatic deficiency, resulting in the accumulation of certain intermediates from the valine catabolism pathway. This disrupts the pyruvate dehydrogenase complex and the mitochondrial respiratory chain, with consequent cellular damage. Patients present with a variable age of onset and a wide spectrum of clinical features. The Leigh syndrome phenotype is the most frequently reported form of the disease. Herein, we report a case of a male with ECHS1 deficiency who was diagnosed at 8 years of age. He presented severe dystonia, hyperlordosis, moderate to severe kyphoscoliosis, great difficulty in walking, and severe dysarthria. A valine-restricted and total fat-restricted diet was considered as a therapeutic option after the genetic diagnosis. An available formula that restricted branched-chain amino acids and especially restricted valine was used. We also restricted animal protein intake and provided a low-fat diet that was particularly low in dairy fat.
This protein- and fat-restricted diet was initiated with adequate tolerance and adherence. After three years, the patient noticed an improvement in dystonia, especially in walking. He currently requires minimal support to walk or stand. Therefore, he has enhanced his autonomy to go to school or establish a career for himself. His quality of life and motivation for treatment have greatly increased.
There is still a substantial lack of knowledge about this rare disorder, especially knowledge about future effective treatments. However, early diagnosis and treatment with a valine- and fat-restricted diet, particularly dairy fat-restricted diet, appeared to limit disease progression in this patient with ECHS1 deficiency.
烯酰辅酶 A 水合酶短链 1（ECHS1）是一种关键的线粒体酶，参与缬氨酸分解代谢和脂肪酸β氧化。ECHS1 基因突变导致酶缺乏，导致缬氨酸分解代谢途径中的某些中间产物积累。这会破坏丙酮酸脱氢酶复合物和线粒体呼吸链，导致细胞损伤。患者的发病年龄和临床表现差异很大。 Leigh 综合征表型是该病最常报告的形式。在此，我们报告了一例 ECHS1 缺乏症男性患者，他在 8 岁时被诊断出患有该疾病。他表现出严重的肌张力障碍、过度脊柱前凸、中重度脊柱后凸、行走困难和严重构音障碍。在基因诊断后，考虑了限制缬氨酸和总脂肪的饮食作为治疗选择。使用了一种限制支链氨基酸、特别是限制缬氨酸的配方。我们还限制了动物蛋白的摄入，并提供了一种低脂饮食，特别是限制了乳脂。
这种蛋白质和脂肪限制饮食具有足够的耐受性和依从性。三年后，患者注意到肌张力障碍有所改善，特别是在行走方面。他目前需要最小的支持来行走或站立。因此，他提高了自己上学或为自己创业的自主性。他的生活质量和治疗意愿都有了很大的提高。
对于这种罕见疾病，我们仍然缺乏大量的知识，特别是关于未来有效治疗方法的知识。然而，早期诊断和限制缬氨酸和脂肪的饮食治疗，特别是限制乳脂的饮食治疗，似乎限制了 ECHS1 缺乏症患者的疾病进展。
