摘要：Abstract Background Citrin, encoded by SLC25A13, is a component of the malate-aspartate shuttle, which is the main NADH-transporting system in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD), which usually resolves within the first year of life. However, small numbers of adults with citrin deficiency develop hyperammonemic encephalopathy, adult-onset type {II} citrullinemia (CTLN2), which leads to death due to cerebral edema. Liver transplantation is the only definitive therapy for patients with CTLN2. We previously reported that a lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula is notably effective for patients with NICCD. Citrin deficiency may impair the glycolysis in hepatocytes because of an increase in the cytosolic NADH/NAD+ ratio, leading to an energy shortage. {MCT} administration can provide energy to hepatocytes and was expected to have a good effect on CTLN2. Methods An {MCT} supplementation therapy under a low-carbohydrate formula was administered to five patients with CTLN2. Four of the patients had episodes of hyperammonemic encephalopathy, and one patient had postprandial hyperammonemia with no symptoms. Results One of the patients displaying hyperammonemic encephalopathy completely recovered with all normal laboratory findings. Others notably improved in terms of clinical and or laboratory findings with no hyperammonemic symptoms; however, the patients displayed persistent mild citrullinemia and occasionally had postprandial mild hyperammonemia most likely due to an irreversible change in the liver. Conclusions An {MCT} supplement can provide energy to hepatocytes and promote hepatic lipogenesis, leading to a reduction in the cytosolic NADH/NAD+ ratio. {MCT} supplementation under a low-carbohydrate formula could be a promising therapy for {CTLN2} and should also be used to prevent {CTLN2} to avoid irreversible liver damage.
关键词：Neonatal intrahepatic cholestasis (NICCD); Adult-onset type II citrullinemia (CTLN2); Citrin deficiency; Medium-chain triglycerides (MCT); SLC25A13; Malate-aspartate shuttle
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