Treatment of a citrin‐deficient patient at the early stage of adult‐onset type II citrullinaemia with arginine and sodium pyruvate

Abstract

Citrin deficiency is a common congenital metabolic defect not only in East Asian populations but also in other populations around the world. It has been shown that although liver transplantation is ultimately required in many patients to prevent neurological decompensation associated with hyperammonaemia, arginine is effective in lowering ammonia in hyperammonaemic patients, and a high-protein low-carbohydrate diet may provide some benefit to infants in improving failure to thrive. In the present study, the clinical symptoms and laboratory findings are reported for a 13-year-old citrin-deficient girl in the early stage of adult-onset type II citrullinaemia (CTLN2), and the therapeutic effect of orally administered arginine and sodium pyruvate was investigated. The patient complained of anorexia, lethargy, fatigue and poor growth, and showed laboratory findings typical of CTLN2; elevated levels of plasma citrulline, threonine-to-serine ratio, and serum pancreatic secretory trypsin inhibitor. Oral administration of arginine and sodium pyruvate for over 3 years improved her clinical symptoms and has almost completely normalized her laboratory findings. It is suggested that the administration of arginine and sodium pyruvate with low-carbohydrate meals may be an effective therapy in patients with citrin deficiency in order either to prolong metabolic normalcy or to provide a safer and more affordable alternative to liver transplantation.

Mechanism for increased hepatic glycerol synthesis in the citrin/mitochondrial glycerol-3-phosphate dehydrogenase double-knockout mouse: Urine glycerol and glycerol 3-phosphate as potential diagnostic markers of human citrin deficiency

“…Our previous study also showed that Pyr ameliorates the deficit in ureogenesis in the perfused liver [16]. Our present results are consistent with the finding that treatment with Na-Pyr improves the clinical outcome citrin-deficient patients [35,36]. Although further work is needed to clarify the mechanism(s) in which Pyr improves liver metabolism in citrin-deficient patients, our present results further support the effectiveness of Pyr as a treatment regime.…”

Treatment with Lactose (Galactose)-Restricted and Medium-Chain Triglyceride-Supplemented Formula for Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency

“…For CTLN2, clinical benefit has been demonstrated with liver transplantation (Saheki et al 2010). Recently, a favorable result was reported in one patient with therapy using sodium pyruvate and arginine under the low carbohydrate formula (Mutoh et al 2008).…”

Effects of supplementation on food intake, body weight and hepatic metabolites in the citrin/mitochondrial glycerol-3-phosphate dehydrogenase double-knockout mouse model of human citrin deficiency

“…throughout life including growth retardation and hypoglycemia in infancy, fatty liver, hypertriglyceridemia, pancreatitis and hepatocellular carcinoma [5][6][7][8][9][10][11][12][13][14][15][16][17]. Citrin has been identified as the hepatic isoform of the mitochondrial aspartate-glutamate carrier (AGC) [18], known to participate in the cytosolic synthesis of proteins, nucleotides and urea through supplying mitochondrial-derived aspartate.…”