Treatment of adult-type citrullinemia with administration of citrate.

Abstract

A 48-year-old man who showed a regular diurnal fluctuation of blood ammonia level was diagnosed as adult-type citrullinemia with quantitative estimation of plasma amino acids and urea cycle enzymes in the liver. The restriction of daily protein intake less than 50 g and oral administration of lactulose had no effect on the blood ammonia level. The efficacy of four amino acid solutions which had been used in order to improve the hepatic encephalopathy was compared each other in this case. Glutamate-arginine mixture had the same effect as glutamate solution in lowering the blood ammonia level, and glutamate was thought to be essential. Also, oral administration of citrate showed a remarkable effect almost comparable to intravenous administration of glutamate. Analysis of plasma amino acids 3 hr after citrate administration demonstrated an increase in glutamate and a decrease in citrulline. These observations suggest that a metabolic pathway of citrate -a-ketoglutarate -glutamate -glutamine takes part in disposing free ammonia in the blood, adult-type citrullinemia; diurnal fluctuation of blood ammonia; citrate therapy

Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD)

“…Asparagine may be substituted for them, although it should be noticed that asparagine loads additional nitrogen onto the urea cycle. Citrate has been used effectively in some cases for CTLN2 therapy (Yajima et al 1981). Citrate supplies oxaloacetate via ATP citrate lyase, although it may also supply acetyl-CoA for the synthesis of fatty acids, resulting in fatty liver and hyperlipidemia.…”

Pyruvate ameliorates the defect in ureogenesis from ammonia in citrin-deficient mice

“…1(A)), despite both substances having been reported to be effective treatments in some CTLN2 cases [35,36]. Although Asp is known to be impermeable to the plasma membrane of periportal hepatocytes [37], a specific plasma membrane transporter can import citrate into the liver [38].…”

Diurnal fluctuation of blood ammonia levels in adult-type citrullinemia.

“…Based on these results, it was concluded that hyperammonemia of adult-type citrullinemia could result from the accumulation of free ammonia which was produced from thn catabolism of amino acids absorbed frcm the small intestine and surpassed the urea synthesis of defective urea cycle to flood into the blood. Furthermore, the rise of blood ammonia level at the night of the first fasting day suggested that the circadian rhythm of amino acid-carbohydrate metabolim might superimpcse on the process mentioned above, adult-type citrullinemia; hyperammonemia; diurnal fluctuation A 48-year-old man with adult-type citrullinemia has been described in our previous report (Yajima et al 1981). He showed repetitive episodes of encephalopathy and was diagnosed by quantitative estimation of amino acids and urea cycle enzymes in the liver.…”