Abstract
Citrin plays a role in the transfer of NADH-reducing equivalent from cytosol to mitochondria as part of the malate–aspartate shuttle in liver. Citrin deficiency may cause an impairment of glycolysis due to an increase in the cytosolic NADH/NAD ratio leading to an energy shortage in the liver. Mutations of the SLC25A13 gene are responsible for neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2). Most patients with NICCD show a resolution of symptoms within the first year of life, but some patients present with severe symptoms and require liver transplantation. We treated four patients including three siblings with NICCD by lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula. This formula rapidly improved the clinical condition and laboratory findings. Early treatment was more effective and did not require long-term administration. Lactose (galactose)-restriction can avoid further increase in the cytosolic NADH/NAD ratio in the liver and MCT supplementation can provide energy to hepatic cells by producing an excess of acetyl-CoA in mitochondria. Early treatment with lactose (galactose)-restricted and MCT-supplemented formula is recommended for patients with NICCD and possibly for patients with CTLN2.
Competing interests: None declared.
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Acknowledgements
We would like to thank the late Dr. Keiko Kobayashi (Kagoshima University) for analysis of SLC25A13 in patients 1 and 2.
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Communicated by: John Christodoulou.
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Take-Home Message
Lactose (galactose)-restricted and medium-chain triglyceride-supplemented formula is a promising therapy for neonatal intrahepatic cholestasis caused by citrin deficiency.
References to Electronic Databases
Citrullinemia, type II, adult-onset (CTLN2): OMIM 603471. Citrullinemia, type II, neonatal-onset (neonatal intrahepatic cholestasis caused by citrin deficiency; NICCD): OMIM 605814.
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Hayasaka, K., Numakura, C., Toyota, K., Kimura, T. (2011). Treatment with Lactose (Galactose)-Restricted and Medium-Chain Triglyceride-Supplemented Formula for Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency. In: JIMD Reports - Case and Research Reports, 2011/2. JIMD Reports, vol 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_42
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DOI: https://doi.org/10.1007/8904_2011_42
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