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Adult-onset type II citrullinemia: Current insights and therapy

Authors Hayasaka K, Numakura C

Received 24 August 2018

Accepted for publication 31 October 2018

Published 12 December 2018 Volume 2018:11 Pages 163—170


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Martin H. Maurer

Kiyoshi Hayasaka,1,2 Chikahiko Numakura1

1Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan; 2Department of Pediatrics, Miyukikai Hospital, Kaminoyama, Japan

Abstract: Citrin deficiency is a recessively inherited metabolic disorder with age-dependent clinical manifestations. It causes neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2). Patients with NICCD present with intrahepatic cholestasis in the neonatal period and usually respond to the treatment with medium-chain triglyceride (MCT) supplement and lactose-restricted formula. In adulthood, CTLN2 develops in <10 % of the patients showing hyperammonemic encephalopathy. Patients with CTLN2 required liver transplantation for the most promising prognosis; however, they were successfully treated with MCT supplement with a low carbohydrate formula. Citrin deficiency is caused by mutations in SLC25A13 on chromosome 7q21.3, with a high frequency in East Asia, including Japan. Citrin is aspartate/glutamate transporter in mitochondria, a component of malate-aspartate nicotinamide adenine dinucleotide hydrogen shuttle, and is essential for the hepatic glycolysis. Although the precise pathophysiology of citrin deficiency remains unclear, recent reports for the effective MCT supplement therapy and downregulation of peroxisome proliferator-activated receptor α suggest that citrin deficiency impairs hepatic de novo lipogenesis coupled with glycolysis leading to the energy deficit of hepatocytes. Herein, we review the current therapeutic and pathological understanding of CTLN2.

Keywords: citrin deficiency, CTLN2, neonatal-onset type II citrullinemia, NICCD, hyperammonemia, medium-chain triglyceride

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