Summary
Ultrastructural investigations have been performed on two cases of transient neonatal hyperammonaemia (TNH). This newly recognized metabolic disorder is chiefly characterized by severe hyperammonaemia in the postnatal period, a comatous state, absence of abnormal organic aciduria, normal activity of urea cycle enzymes and, usually, complete recovery. The aetiology is presently unknown.
Electron microscopy uncovered rather congruent alterations of hepatocyte structure, with a wide spectrum of mitochondrial lesions, an increase of autophagous bodies with organelle remnants, and changes in the excretory apparatus. Thus, in contrast to some of the hereditary disorders of the urea cycle, no specific structural changes could be found in TNH. This finding is in line with the observation of normal activities of main urea enzymes in these cases, and indicates that a different biochemical system may be pathogenetically involved in TNH.
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References
Bachmann C (1974) Urea cycle. In: Nyhan WL (ed) Heritable disorders of amino acid metabolism. Wyley, New York, p 361
Bachmann C, Colombo JP (1982) Hyperammonämie: Ein Vorschlag für das diagnostische und therapeutische Vorgehen. Pädiatrie und Pädologie 17:141–148
Bachmann C, Colombo JP, Jaggi K (1983) N-acetylglutamate synthetase (NAGS) deficiency: diagnosis, clinical observations and treatment. In: Lowenthal A, Mori A, Marescau B (eds) Urea cycle diseases. Plenum Publication Corporation, p 39
Ballard RA, Vinocur B, Reynolds JW, Wennberg RP, Merritt A, Sweetman L, Nyhan WL (1978) Transient hyperammonemia of the preterm infant. N Engl J Med 299:920–925
Brown T, Hug G, Lansky L, Bove K, Scheve A, Ryan M, Brown H, Schubert WK, Partin JC, Lloyd-Still J (1976) Transiently reduced activity of carbamylphosphate synthetase and ornithine transcarbamylase in liver of children with Reye's syndrome. N Engl J Med 294:861–867
Colombo JP (1971) Congenital disorders of the urea cycle and ammonia detoxification. Monogr Paediatr 1, Karger, Basel
Colombo JP, Bürgi W, Richterich R (1967) Congenital lysine intolerance with periodic ammonia intoxication: a defect in L-lysine degradation. Metabolism 16:910–925
Fell V, Pollitt RJ, Sampson GA, Wright T (1974) Ornithinemia, hyperammonemia, and homocitrullinuria: a disease associated with mental retardation and possibly caused by defective mitochondrial transport. Am J Dis Child 127:752–756
Gatfield PD, Taller E, Wolfe DM (1975) Hyperornithinemia, hyperammonemia, and homocitrullinuria associated with decreased carbamylphosphate synthetase I activity. Pediatr Res 9:488–497
Goldberg RN, Cabal LA, Sinatra FR, Plajstek CE, Hodgman JE (1978) Hyperammonemia associated with perinatal asphyxia. Clin Res 26:198A
Hug G, Kline J, Schubert W (1978) Liver ultrastructure: dissimilarity between Reye's syndrome and heritable defects of carbamyl phosphate synthetase or ornithine transcarbamylase. Pediatr Res 12:437
Jaeken J, Devlieger H, Casaer P, Eggermont E (1982a) Transient neonatal hyperammonemia and herpes simplex infection (letter). Lancet II:272
Jaeken J, Devlieger H, Casaer P, Eggermont E (1982b) Transient hyperammonemia in the preterm infant (letter to the editor). Neurology 32:1070–1071
Kekomäki M, Visakorpi JK, Perheentupa J, Saxén L (1967) Familial protein intolerance with deficient transport of basic amino acids: an analysis of 10 patients. Acta Paediatr Scand 56:617–630
Latham PS, La Brecque DR, Kashgarian L, Klatskin G (1977) A comparative ultrastructural study of inherited urea cycle enzyme deficiency states and Reye's syndrome. Gastroenterology 73:1230
Le Guennec JC, Qureshi IA, Bard H, Siriez JY, Letarte J (1980) Transient hyperammonemia in an early preterm infant. J Pediatr 96:470–472
Mahoney MJ (1976) Organic acidemias. Clin Perinatol 3:61–78
Mihatsch MJ, Riede UN, Ohnacker H, Wick H, Bachmann C (1974) Liver morphology in a case of citrullinemia (a light and electron microscopic study). Beitr Pathol 151:200–207
Murphy JV, Marquardt K (1982) Asymptomatic hyperammonemia in patients receiving valproic acid. Arch Neurol 39:591–592
Nyhan WL, Rubio V, Jordá A, Grisolia S, Gutierez F, Canosa C (1982) Transient hyperammonemia in infants with and without organic acidemia. Adv Exp Med Biol 153:331–338
Shapiro JM, Schaffner F, Tallan HH, Gaull GE (1980) Mitochondrial abnormalities of liver in primary ornithine transcarbamylase deficiency. Pediatr Res 14:735–739
Shih VE, Efron ML, Moser HW (1969) Hyperornithinemia, hyperammonemia, and homocitrullinuria: a new disorder of amino acid metabolism associated with myoclonic seizures and mental retardation. Am J Dis Child 117:83–92
Sinatra F, Yoshida T, Applebaum M, Mason W, Hoogenraad NJ, Sunshine P (1975) Abnormalities of carbamylphosphate synthetase and ornithine transcarbamylase in liver of patients with Reye's syndrome. Pediatr Res 9:829–833
Snodgrass PJ, De Long GR (1976) Urea-cycle enzyme deficiencies and an increased nitrogen load producing hyperammonemia in Reye's syndrome. N Engl J Med 294:855–860
Tollefsen SE, McCabe ERB, Goodman SI (1980) Neonatal hyperammonemia. Pediatrics 65:1197–1198
Zimmermann A, Bachmann C, Colombo JP (1981) Ultrastructural pathology in congenital defects of the urea cycle: ornithine transcarbamylase and carbamylphosphate synthetase deficiency. Virchows Arch [Pathol Anat] 393:321–331
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Zimmermann, A., Bachmann, C., Hügger, I. et al. Liver pathology in transient neonatal hyperammonemia. Vichows Archiv A Pathol Anat 402, 25–33 (1983). https://doi.org/10.1007/BF00695046
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DOI: https://doi.org/10.1007/BF00695046