Citrin deficiency is a hereditary disorder caused by SLC25A13 mutations and manifests as neonatal intrahepatic cholestasis (NICCD), failure to thrive and dyslipidemia (FTTDCD), and adult‐onset type II citrullinemia (CTLN2). Citrin is a component of the malate‐aspartate nicotinamide adenine dinucleotide hydrogen (NADH) shuttle, an essential shuttle for hepatic glycolysis. Hepatic glycolysis and the coupled lipogenesis are impaired in citrin deficiency. Hepatic lipogenesis plays a significant role in fat supply during growth spurt periods: the fetal period, infancy, and puberty. Growth impairment in these periods is characteristic of citrin deficiency. Hepatocytes with citrin deficiency cannot use glucose and fatty acids as energy sources due to defects in the NADH shuttle and downregulation of peroxisome proliferator‐activated receptor α (PPARα), respectively. An energy deficit in hepatocytes is considered a fundamental pathogenesis of citrin deficiency. Medium‐chain triglyceride (MCT) supplementation with a lactose‐restricted formula and MCT supplementation under a low‐carbohydrate diet are recommended for NICCD and CTLN2, respectively. MCT supplementation therapy can provide energy to hepatocytes, promote lipogenesis, correct the cytosolic NAD⁺/NADH ratio via the malate‐citrate shuttle and improve ammonia detoxification, and it is a reasonable therapy for citrin deficiency. It is very important to administer MCT at a dose equivalent to the liver's energy requirements in divided doses with meals. MCT supplementation therapy is certainly promising for promoting growth spurts during infancy and adolescence and for preventing CTLN2 onset. Intravenous administration of solutions containing fructose is contraindicated, and persistent hyperglycemia should be avoided due to glucose intoxication for patients receiving hyperalimentation or with complicating diabetes.

中文翻译：

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citrin缺乏症的代谢基础及治疗

Citrin 缺乏症是一种由SLC25A13引起的遗传性疾病突变并表现为新生儿肝内胆汁淤积症 (NICCD)、生长发育障碍和血脂异常 (FTTDCD) 和成人发病的 II 型瓜氨酸血症 (CTLN2)。Citrin 是苹果酸-天冬氨酸烟酰胺腺嘌呤二核苷酸氢 (NADH) 穿梭机的一种成分，NADH 穿梭机是肝糖酵解的必需穿梭机。肝糖酵解和耦合脂肪生成在 citrin 缺乏中受损。肝脏脂肪生成在生长突增期（胎儿期、婴儿期和青春期）的脂肪供应中起着重要作用。这些时期的生长障碍是citrin缺乏的特征。由于 NADH 穿梭缺陷和过氧化物酶体增殖物激活受体 α (PPARα) 的下调，citrin 缺乏的肝细胞不能使用葡萄糖和脂肪酸作为能量来源。肝细胞中的能量缺乏被认为是citrin缺乏症的基本发病机制。对于 NICCD 和 CTLN2，分别推荐含有乳糖限制配方的中链甘油三酯 (MCT) 补充剂和低碳水化合物饮食下的 MCT 补充剂。MCT补充疗法可为肝细胞提供能量，促进脂肪生成，纠正胞质NAD⁺ /NADH 比值通过苹果酸-柠檬酸盐穿梭，提高氨解毒能力，是 citrin 缺乏症的合理疗法。以相当于肝脏能量需求的剂量分次服用 MCT 是非常重要的。MCT 补充疗法肯定有希望促进婴儿期和青春期的生长突增以及预防 CTLN2 发作。含有果糖的溶液是禁忌的，对于接受高营养的患者或合并糖尿病的患者，应避免由于葡萄糖中毒引起的持续高血糖。