Abstract
Citrullinaemia is a rare inborn error of urea-cycle metabolism. Two affected children are reported in whom progressive metabolic instability suggested the possibility of hepatopathy or an ongoing hepatic mitochondrial injury. A percutaneous liver biopsy was performed in each patient. Electron-microscopic findings were similar in both cases. Approximately 20% of the mitochondria were abnormally enlarged with paracrystalline inclusions and electron-dense bodies of different sizes and shapes present in the matrix. The specificity of these findings is discussed in the context of previous reports of ultrastructural abnormalities in the hepatocytes of patients with inborn errors of the urea cycle. It is speculated that the mitochondrial abnormalities in citrullinaemia may be related to the accumulation of citrulline in the mitochondria which may eventually manifest as metabolic instability.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Bradford NM, McGivan JD (1980) Evidence for the existence of an ornithine/citrulline antiporter in rat liver mitochondria. FEBS Lett 113: 294–298.
Brusilow SW, Horwich AL (1995) Urea cycle enzymes. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Diseases, 7th edn. New York: McGraw-Hill, 629–663.
Cohen NS, Cheung C-W, Raijman L (1987) Channeling of extramitochondrial ornithine to matrix ornithine transcarbamylase. J Biol Chem 262: 203–208.
Flick JA, Latham PS, Perman JA, Brusilow SW (1986) Hepatic involvement in argininosuccinase deficiency (ALD). Pediatr Res 20: 239A.
Gamble JG, Lehninger AL (1973) Transport of ornithine and citrulline across the mitochondrial membrane. J Biol Chem 248: 610–618.
Hug G, Kline J, Schubert W (1978) Liver ultrastructure: dissimilarity between Reye's syndrome and heritable defect of carbamyl phosphate synthetase or ornithine transcarbamylase. Pediatr Res 12: 437.
Indiveri C, Tonazzi A, Palmieri F (1992) Identification and purification of the ornithine/citrulline carrier from rat liver mitochondria. Eur J Biochem 207: 449–454.
Indiveri C, Palmieri L, Palmieri F (1994) Kinetic characterization of the reconstituted ornithine carrier from rat liver mitochondria. Biochim Biophys Acta 1188: 293–301.
Jan D, Poggi F, Jouvet P, et al (1994) Definitive cure of hyperammonemia by liver transplantation in urea cycle defects: report of three cases. Transplantation Proc 26: 188.
LaBrecque DR, Latham PS, Riely CA, Hsia YE, Klatskin G (1979) Heritable urea cycle enzyme deficiency-liver disease in 16 patients. J Pediatr 94: 580–587.
Latham PS, LaBrecque DR, Kashgarian M, Klatskin G (1977) A comparative ultrastructural study of inherited urea cycle enzyme deficiency states and Reye's syndrome (RS). Gastroenterology 73: A-32/1230.
Latham PS, LaBrecque DR, McReynolds JW, Klatskin G (1984) Liver ultrastructure in mitochondrial urea cycle enzyme deficiencies and comparison with Reye's syndrome. Hepatology 4: 404–407.
Longhi R, Buttè C, Valsasina R, Rossi L, Borzani M (1981) Mitochondrial abnormalities in a male with ornithine transcarbamylase deficiency (OTC). Pediatr Res 15: 634.
Mei MH, An W, Zhang BH, Shao Q, Gong DZ (1993) Hepatic stimulator substance protects against liver failure induced by carbon tetrachloride poisoning in mice. Hepatology 17: 638–644.
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 Path Bd 151: 200–207.
O'Connor JE, Renau-Piqueras J, Grisolia S (1984) Effects of urease-induced hyperammonemia in mouse liver. Virchows Arch (Cell Pathol) 46: 187–197.
Parsons HG, Scott RB, Pinto A, Carter RJ, Snyder FF (1987) Argininosuccinic aciduria: long-term treatment with arginine. J Inher Metab Dis 10: 152–161.
Ramadan AA, Yousif WB, Ali AM (1992) The effect of methotrexate on small intestine of the mouse. III. Mitochondria and succinic dehydrogenase. Funct Dev Morphol 2: 3–9.
Shapiro JM, Schaffner F, Tallan HH, Gaull GE (1980) Mitochondrial abnormalities of liver in primary ornithine transcarbamylase deficiency. Pediatr Res 14: 735–739.
Wick H, Bachmann C, Baumgartner R, et al (1973) Variants of citrullinemia. Arch Dis Child 48: 636–641.
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.
Zimmermann A, Bachmann C, Högger I, et al (1983) Liver pathology in transient neonatal hyperammonemia. Virchows Arch (Pathol Anat) 402: 25–33.
Zimmermann A, Bachmann C, Baumgartner R (1986) Severe liver fibrosis in arginosuccinic aciduria. Arch Pathol Lab Med 110: 136–140.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zamora, S.A., Pinto, A., Scott, R.B. et al. Mitochondrial abnormalities of liver in two children with citrullinaemia. J Inherit Metab Dis 20, 509–516 (1997). https://doi.org/10.1023/A:1005341228486
Issue Date:
DOI: https://doi.org/10.1023/A:1005341228486