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リエゾンラボ研究会
発表内容

Title:
Citrin, a mitochondrial aspartate glutamate carrier, deficiency, a newly-established disease entity -Pathogenesis, pathophysiology and treatment of neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2) ?

Takeyori Saheki
Institute of Resource Development and Analysis, Kumamoto University

Abstract:
In 1999, we discovered SLC25A13 as the causative gene for adult-onset type II citrullinemia, which is characterized by neuropsychiatric symptoms such as disorientation, abnormal behavior, delirium and coma accompanied by hyperammonemia and citrullinemia. SLC25A13 encodes a mitochondrial solute carrier named citrin, which was found to be a liver-type aspartate glutamate carrier. DNA diagnosis for SLC25A13 mutations enabled to disclose a kind of neonatal hepatitis, now called NICCD (neonatal intrahepatic cholestasis caused by citrin deficiency), in which major findings are hyperbilirubinemia, galactosemia, hypoproteinemia and multiple aminoacidemia including citrulline, arginine, phenylalanine, tyrosine and methionine. These results led us to establish citrin deficiency as a disease entity. In this lecture, I will present our results on pathophysiology and treatment of the disease, emphasizing unique food taste of the patients in relation to issues in the treatment.

References:
Kobayashi K et al. The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein. Nat Genet. 1999;22(2):159-63.

Palmieri L et al. Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. EMBO J. 2001;20(18):5060-9.

Saheki T et al. Reduced carbohydrate intake in citrin-deficient subjects. J Inherit Metab Dis 2008;31(3):386-94.

Saheki T et al. Citrin deficiency and current treatment concepts. Mol Genet Metab. 2010;100 Suppl 1:S59-64.