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Yamagata Med J（ISSN 0288-030X）2021；39（1）
：52-60早坂
DOI 10.15022/00004900
Early treatment with medium-chain fatty acids for citrin deficiency
improves the prognosis
Kiyoshi Hayasaka
Department of Pediatrics, Yamagata University Scool of Medicine
Department of Pediatrics, Miyukikai Hospital, Social Medical Corporation Miyukikikai
ABSTRACT
Citrin deficiency（CD）is an autosomal hereditary disorder caused by mutations in SLC25A13.
It manifests with age-dependent clinical manifestations: neonatal intrahepatic cholestasis（NICCD）,
failure to thrive and dyslipidemia（FTTDCD）
, and adult-onset type II citrullinemia（CTLN2）.
Citrin is a component of the malate-aspartate nicotinamide adenine dinucleotide hydrogen（NADH）
shuttle. Hepatocytes of CD cannot use glucose and fatty acid as energy sources due to defects in
the NADH shuttle and downregulation of peroxisome proliferator-activated receptor α（PPARα ）,
respectively. Energy deficit of hepatocytes is considered a fundamental pathogenesis of CD. Medium
chain triglyceride（MCT）supplementation with lactose-restricted formula and MCT supplementation
under a low-carbohydrate diet are recommended for NICCD and CTLN2, respectively. MCT
supplementation therapy can provide energy to the hepatocytes, promote lipogenesis and glycogenesis,
correct the cytosolic NAD＋/NADH ratio and improve ammonia metabolism and early treatment can
prevent irreversible damage. MCT should be administered at a dose equivalent to the liver’
s energy
requirements in divided doses with meals. MCT supplementation therapy is promising for promoting
growth spurts during infancy and adolescence and for preventing CTLN2 onset. Intravenous
administration of the solutions containing fructose is contraindicated, and persistent hyperglycemia
should be avoided due to glucose intoxication for the patients receiving hyperalimentation or with
complicating diabetes.
Keywords: citrin deficiency, malate-aspartate shuttle，neonatal intrahepatic cholestasis caused by
citrin deficiency, adult-onset type II citrullinemia, medium chain triglycerides
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