Classical organic acidemias (OAs) result from defective mitochondrial catabolism of branched‐chain amino acids (BCAAs). Abnormal mitochondrial function relates to oxidative stress, ectopic lipids and insulin resistance (IR). We investigated whether genetically impaired function of mitochondrial BCAA catabolism associates with cardiometabolic risk factors, altered liver and muscle energy metabolism, and IR. In this case‐control study, 31 children and young adults with propionic acidemia (PA), methylmalonic acidemia (MMA) or isovaleric acidemia (IVA) were compared with 30 healthy young humans using comprehensive metabolic phenotyping including in vivo ³¹P/¹H magnetic resonance spectroscopy of liver and skeletal muscle. Among all OAs, patients with PA exhibited abdominal adiposity, IR, fasting hyperglycaemia and hypertriglyceridemia as well as increased liver fat accumulation, despite dietary energy intake within recommendations for age and sex. In contrast, patients with MMA more frequently featured higher energy intake than recommended and had a different phenotype including hepatomegaly and mildly lower skeletal muscle ATP content. In skeletal muscle of patients with PA, slightly lower inorganic phosphate levels were found. However, hepatic ATP and inorganic phosphate concentrations were not different between all OA patients and controls. In patients with IVA, no abnormalities were detected. Impaired BCAA catabolism in PA, but not in MMA or IVA, was associated with a previously unrecognised, metabolic syndrome‐like phenotype with abdominal adiposity potentially resulting from ectopic lipid storage. These findings suggest the need for early cardiometabolic risk factor screening in PA.

中文翻译：

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支链氨基酸分解代谢缺陷患者的心脏代谢危险因素聚类：病例对照研究。

经典有机酸血症（OAs）是由支链氨基酸（BCAAs）的线粒体分解代谢缺陷引起的。异常的线粒体功能与氧化应激、异位脂质和胰岛素抵抗 (IR) 相关。我们研究了线粒体 BCAA 分解代谢的遗传功能受损是否与心脏代谢危险因素、肝脏和肌肉能量代谢改变以及 IR 相关。在这项病例对照研究中，31 名患有丙酸血症 (PA)、甲基丙二酸血症 (MMA) 或异戊酸血症 (IVA) 的儿童和年轻人与 30 名健康年轻人使用综合代谢表型进行了比较，包括体内³¹ P/ ¹肝脏和骨骼肌的 H 磁共振波谱。在所有 OA 中，尽管饮食能量摄入符合年龄和性别的建议，但 PA 患者表现出腹部肥胖、IR、空腹高血糖和高甘油三酯血症以及肝脏脂肪堆积增加。相比之下，MMA 患者的能量摄入量通常高于推荐值，并且具有不同的表型，包括肝肿大和骨骼肌 ATP 含量略低。在 PA 患者的骨骼肌中，发现无机磷酸盐水平略低。然而，所有 OA 患者和对照组的肝脏 ATP 和无机磷酸盐浓度没有差异。在IVA患者中，未检测到异常。PA 中 BCAA 分解代谢受损，但在 MMA 或 IVA 中未受损，与先前未识别的、代谢综合征样表型，腹部肥胖可能由异位脂质储存引起。这些发现表明需要在 PA 中进行早期心脏代谢危险因素筛查。