Ornithine loading did not prevent induced hyperammonemia in a patient with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome.
Impairment of urea cycle function in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome is presumably caused, in some patients, by deficient transport of ornithine from cytoplasm into mitochondria. We studied the effect of L-ornithine on L-alanine-induced hyperammonemia in a French-Canadian proband with the syndrome by giving: a 90-min intravenous alanine load (6.6 mmol/kg) together with ornithine (1.1 mmol/kg); an intravenous ornithine bolus (0.3 mmol/kg) followed by ornithine infusion (1.1 mmol/kg) 90 min prior to loading with alanine and ornithine; ornithine supplementation per os (1 g, four times daily X 2 wk) prior to loading with alanine and ornithine. Blood ammonia increased from high normal values to 975, 990, and 750 mumol/liter (normal less than 70) and urinary orotic acid from trace to 539, 494, and 1296 mumol/mmol creatinine (normal 5-11) after the respective loads. Plasma alanine peaked at 1.56-4.24 mmol/liter and ornithine at 1.29-1.95 mmol/liter, but other amino acids were stable. Therefore, ornithine loading did not protect this hyperornithinemia-hyperammonemia-homocitrullinuria patient from hyperammonemia induced by amino-nitrogen loading. Renal fraction excretion of citrulline, lysine, ornithine, glycine, alanine, and tyrosine increased more than 3-fold during ornithine priming, whereas all amino acids were excreted in excess after alanine + ornithine loads; homocitrulline excretion remained unchanged; some urine collections indicated "negative reabsorption" (i.e. apparent secretion) of lysine, histidine, and citrulline. Dietary supplementation with ornithine could deplete lysine pools by impairing lysine reabsorption.
D000409:Alanine / Q000494:pharmacology; D000592:Amino Acid Metabolism, Inborn Errors / Q000188:drug therapy* / Q000378:metabolism; D000596:Amino Acids / Q000097:blood / Q000652:urine; D000641:Ammonia / Q000097:blood*; D002648:Child; D002956:Citrulline / Q000031:analogs & derivatives* / Q000652:urine; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008297:Male; D009952:Ornithine / Q000097:blood* / Q000378:metabolism / Q000494:pharmacology; D009963:Orotic Acid / Q000652:urine; D013577:Syndrome
D000596:Amino Acids; C001352:homocitrulline; D002956:Citrulline; D009963:Orotic Acid; D000641:Ammonia; D009952:Ornithine; D000409:Alanine