Citrin deficiency is a pan-ethnic and highly prevalent mitochondrial disease with three different stages: neonatal intrahepatic cholestasis (NICCD), a relatively mild adaptation stage, and type II citrullinemia in adulthood (CTLN2). The cause is the absence or dysfunction of the calcium-regulated mitochondrial aspartate/glutamate carrier 2 (AGC2/SLC25A13), also called citrin, which imports glutamate into the mitochondrial matrix and exports aspartate to the cytosol. In citrin deficiency, these missing transport steps lead to impairment of the malate-aspartate shuttle, gluconeogenesis, amino acid homeostasis, and the urea cycle. In this review, we describe the geological spread and occurrence of citrin deficiency, the metabolic consequences and use our current knowledge of the structure to predict the impact of the known pathogenic mutations on the calcium-regulatory and transport mechanism of citrin.

Citrin 缺乏症是一种泛种族和高度流行的线粒体疾病，分为三个不同阶段：新生儿肝内胆汁淤积症 (NICCD)、相对温和的适应阶段和成年期 II 型瓜氨酸血症 (CTLN2)。原因是钙调节的线粒体天冬氨酸/谷氨酸载体 2 (AGC2/SLC25A13)（也称为 citrin）缺失或功能障碍，它将谷氨酸输入线粒体基质并将天冬氨酸输出到胞质溶胶。在 citrin 缺乏症中，这些缺失的运输步骤会导致苹果酸-天冬氨酸穿梭、糖异生、氨基酸稳态和尿素循环受损。在这篇综述中，我们描述了 citrin 缺乏症的地质传播和发生，