Congenital Lysine Intolerance with Periodic Ammonia Intoxication: A Defect in L-Lysine Degradation

Abstract A 3-month-old girl is described who has been suffering since birth from vomiting and episodes of coma. During these comatous states, abnormally high concentrations of blood ammonia (around 500 μg./100 ml.) were found. The routine liver function tests showed no signs of inflammation or cirrhosis. The activities of urea cycle enzymes (carbamoyl-phosphate-synthetase, ornithine-carbamoyl transferase, elevage enzyme and arginase) and enzymes of ammonia detoxication (glutamate dehydrogenase, GOT, GPT, glutaminase) of a liver biopsy were normal, compared to controls. Chromatographic studies of plasma amino acids during normal or high protein intake revealed an increase in the concentrations of lysine and arginine. Lysine is a potent competitive inhibitor of arginase. On a normal protein intake the inhibitory effect of lysine may become so great that arginase activity is depressed, urea formation slowed down and ammonia detoxication impaired. During a lysine load the child became comatous, the blood ammonia rose to 680 μg/100 ml., and the activity of red cell arginase was depressed. The cause of the hyperlysinemia is an impairment in the degradation of lysine due to a partial defect of lysine: NAD-oxido-reductase (deaminating), which was measured on the liver biopsy material.