Medium-chain triglyceride supplementation under a low-carbohydrate formula is a promising therapy for adult-onset type II citrullinemia
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2014-01-01
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| Series: | Molecular Genetics and Metabolism Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426913000074 |
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| author | Kiyoshi Hayasaka Chikahiko Numakura Kentaro Toyota Satoru Kakizaki Hisayoshi Watanabe Hiroaki Haga Hiroshi Takahashi Yoshimi Takahashi Mieko Kaneko Mitsunori Yamakawa Hiroyuki Nunoi Takeo Kato Yoshiyuki Ueno Masatomo Mori |
| author_facet | Kiyoshi Hayasaka Chikahiko Numakura Kentaro Toyota Satoru Kakizaki Hisayoshi Watanabe Hiroaki Haga Hiroshi Takahashi Yoshimi Takahashi Mieko Kaneko Mitsunori Yamakawa Hiroyuki Nunoi Takeo Kato Yoshiyuki Ueno Masatomo Mori |
| author_sort | Kiyoshi Hayasaka |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T06:20:54Z |
| format | Article |
| id | doaj.art-770744e4e35944e69abc7f06ff045e47 |
| institution | Directory Open Access Journal |
| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-12-22T06:20:54Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj.art-770744e4e35944e69abc7f06ff045e472022-12-21T18:35:58ZengElsevierMolecular Genetics and Metabolism Reports2214-42692014-01-011C425010.1016/j.ymgmr.2013.12.002Medium-chain triglyceride supplementation under a low-carbohydrate formula is a promising therapy for adult-onset type II citrullinemiaKiyoshi Hayasaka0Chikahiko Numakura1Kentaro Toyota2Satoru Kakizaki3Hisayoshi Watanabe4Hiroaki Haga5Hiroshi Takahashi6Yoshimi Takahashi7Mieko Kaneko8Mitsunori Yamakawa9Hiroyuki Nunoi10Takeo Kato11Yoshiyuki Ueno12Masatomo Mori13Dept. of Pediatrics, Yamagata University School of Medicine, Yamagata, JapanDept. of Pediatrics, Yamagata University School of Medicine, Yamagata, JapanDept. of Pediatrics, Yamagata University School of Medicine, Yamagata, JapanDept. of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, JapanDept. of Gastroenterology, Yamagata University School of Medicine, Yamagata, JapanDept. of Gastroenterology, Yamagata University School of Medicine, Yamagata, JapanDept. of Internal Medicine, Prefectural Ninohe Hospital, Iwate, JapanDept. of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology, Yamagata University School of Medicine, Yamagata, JapanDept. of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, JapanDept. of Pathological Diagnostics, Yamagata University School of Medicine, Yamagata, JapanDivision of Pediatrics, Dept. of Reproductive and Developmental Medicine, University of Miyazaki, Miyazaki, JapanDept. of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology, Yamagata University School of Medicine, Yamagata, JapanDept. of Gastroenterology, Yamagata University School of Medicine, Yamagata, JapanDept. of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, JapanBackground: 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.http://www.sciencedirect.com/science/article/pii/S2214426913000074Neonatal intrahepatic cholestasis (NICCD)Adult-onset type II citrullinemia (CTLN2)Citrin deficiencyMedium-chain triglycerides (MCT)SLC25A13Malate-aspartate shuttle |
| spellingShingle | Kiyoshi Hayasaka Chikahiko Numakura Kentaro Toyota Satoru Kakizaki Hisayoshi Watanabe Hiroaki Haga Hiroshi Takahashi Yoshimi Takahashi Mieko Kaneko Mitsunori Yamakawa Hiroyuki Nunoi Takeo Kato Yoshiyuki Ueno Masatomo Mori Medium-chain triglyceride supplementation under a low-carbohydrate formula is a promising therapy for adult-onset type II citrullinemia Molecular Genetics and Metabolism Reports Neonatal intrahepatic cholestasis (NICCD) Adult-onset type II citrullinemia (CTLN2) Citrin deficiency Medium-chain triglycerides (MCT) SLC25A13 Malate-aspartate shuttle |
| title | Medium-chain triglyceride supplementation under a low-carbohydrate formula is a promising therapy for adult-onset type II citrullinemia |
| title_full | Medium-chain triglyceride supplementation under a low-carbohydrate formula is a promising therapy for adult-onset type II citrullinemia |
| title_fullStr | Medium-chain triglyceride supplementation under a low-carbohydrate formula is a promising therapy for adult-onset type II citrullinemia |
| title_full_unstemmed | Medium-chain triglyceride supplementation under a low-carbohydrate formula is a promising therapy for adult-onset type II citrullinemia |
| title_short | Medium-chain triglyceride supplementation under a low-carbohydrate formula is a promising therapy for adult-onset type II citrullinemia |
| title_sort | medium chain triglyceride supplementation under a low carbohydrate formula is a promising therapy for adult onset type ii citrullinemia |
| topic | Neonatal intrahepatic cholestasis (NICCD) Adult-onset type II citrullinemia (CTLN2) Citrin deficiency Medium-chain triglycerides (MCT) SLC25A13 Malate-aspartate shuttle |
| url | http://www.sciencedirect.com/science/article/pii/S2214426913000074 |
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