Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Episodic Hyperammonemia in Adult Siblings With Hyperornithinemia, Hyperammonemia, and Homocitrullinuria Syndrome

Episodic Hyperammonemia in Adult Siblings With Hyperornithinemia, Hyperammonemia, and... Abstract • A 39-year-old man and his 42-year-old sister, both vegetarians, had episodic confusion for many years, but their mental function was normal between those episodes. They were recently diagnosed with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. Hyperammonemia was documented during an episode of confusion in the male sibling but not in his sister. Both had elevated plasma ornithine, glutamine, and alanine levels and persistently low plasma lysine levels. Homocitrulline was present in their urine, and orotic aciduria and orotidinuria developed in the male sibling following ingestion of allopurinol. Studies on their cultured skin fibroblasts showed deficient metabolism of ornithine, indicating a defect in ornithine transport across the mitochondrial membrane. During therapy with citrulline and phenylbutyrate sodium, plasma ornithine levels increased in both patients, while plasma levels of glutamine and alanine decreased to normal. Since therapy started, their clinical conditions have also improved, and no recurrent neurologic dysfunction has occurred during a follow-up period of 20 months. References 1. Snyderman SE. Clinical aspects of disorders of the urea cycle . Pediatrics . 1981;68:284-289. 2. Batshaw ML, Roan Y, Jung AL, Rosenberg LA, Brusilow SW. Cerebral dysfunction in asymptomatic carriers of ornithine transcarbamylase deficiency . N Engl J Med . 1980;302:482-485.Crossref 3. DiMagno EP, Lowe JE, Snodgrass PJ, Jones JD. Ornithine transcarbamylase deficiency: a cause of bizarre behavior in man . N Engl J Med . 1986;315:744-777.Crossref 4. Granot E, Matoth I, Lotan C, Shvil Y, Lijovetzky G, Yatziv S. Partial carbamyl phosphate synthetase deficiency, simulating Reye's syndrome, in a 9-year-old girl . Isr J Med Sci . 1986;22:463-465. 5. Lezak MD. Neuropsychological Assessment . 2nd ed. New York, NY: Oxford University Press; 1983:422-429, 556-559. 6. Ramnaraine ML, Tuchman M. Aromatic and nitrogen containing acid separation by high performance liquid chromatography and identification by photodiode array detector . J Chromatogr Sci . 1985;24:549-554.Crossref 7. Brusilow SW, Valle DL. Allopurinol (AP) induced orotidinuria (ODNU): a test of heterozygosity for ornithine transcarbamylase (OTC) deficiency . Pediatr Res . 1987;21:189A. Abstract.Crossref 8. Shih VE, Mandell R, Herzfeld A. Defective ornithine metabolism in cultured skin fibroblasts from patients with the syndrome of hyperornithinemia, hyperammonemia, and homocitrullinuria . Clin Chim Acta . 1982;118:149-157.Crossref 9. Shih VE, Efron ML, Moser HW. Hyperornithinemia, hyperammonemia and homocitrullinuria: a new disorder of amino acid metabolism associated with myoclonic seizures and mental retardation . AJDC . 1969;117:83-92. 10. Wright T, Pollitt R. Psychomotor retardation, epileptic and stuporous attacks, irritability and ataxia associated with ammonia intoxication, high blood ornithine levels and increased homocitrulline in the urine . Proc R Soc Med . 1973;66:221. 11. Gatfield PD, Taller E, Wolfe DM, Haust D. Hyperornithinemia, hyperammonemia and homocitrullinuria associated with decreased carbamylphosphate synthetase I activity . Pediatr Res . 1975;9:488-497.Crossref 12. Hommes FA, Ho CK, Roesel RA, Coryell ME, Gordon BA. Decreased transport of ornithine across the inner mitochondrial membrane as a cause of hyperornithinaemia . J Inherited Metab Dis . 1982;5:41-47.Crossref 13. Oyanagi K, Tsuchiyama A, Itakura Y, et al. The mechanism of hyperammonaemia and hyperornithinaemia in the syndrome of hyperornithinaemia, hyperammonaemia with homocitrullinuria . J Inherited Metab Dis . 1983;6:133-134.Crossref 14. Simell O, Mackenzie S, Clow CL, Scriver CR. Ornithine loading did not prevent induced hyperammonemia in a patient with hyperornithinemiahyperammonemia-homocitrullinemia syndrome . Pediatr Res . 1985;19:1283-1287.Crossref 15. Gjessing LR, Lunde HA, Undrum T, Broch H, Alme A, Lie SO. A new patient with hyperornithinaemia, hyperammonaemia and homocitrullinuria treated early with low protein diet . J Inherited Metab Dis . 1986;9:186-192.Crossref 16. Hommes FA, Roesel RA, Metoki K, Hartlage PL, Dyken PR. Studies on a case of HHH syndrome (hyperammonemia, hyperornithinemia, homocitrullinuria) . Neuropediatrics . 1986;17:48-52.Crossref 17. Rodes M, Ribes A, Pineda M, et al. A new family affected by the syndrome of hyperornithinaemia, hyperammonaemia and homocitrullinuria . J Inherited Metab Dis . 1987;10:73-81.Crossref 18. Koike R, Fujimori K, Yuasa T, Miyatake T, Inoue I, Saheki T. Hyperornithinemia, hyperammonemia and homocitrullinuria: case report and biochemical study . Neurology . 1987;37:1813-1815.Crossref 19. Dionsi Vici C, Bachmann C, Gambarara M, Colombo JP, Sabetta G. Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome: low creatine excretion and effect of citrulline, arginine or ornithine supplement . Pediatr Res . 1987;22:364-367.Crossref 20. Nakajima M, Ishii S, Mito T, et al. Clinical, biochemical and ultrastructural study on the pathogenesis of hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome . Brain Dev . 1988;10:181-185.Crossref 21. Valle D, Simell O. The hyperornithinemias . In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic Basis of Inherited Disease . New York, NY: McGraw-Hill International Book Co; 1989:599-627. 22. James MO, Smith RL, Williams RT, Reidenberg M. The conjugation of phenylacetic acid in man, sub-human primates and some nonprimate species . Proc R Soc Lond . 1972;182:25-35.Crossref 23. Hommes FA, Eller AG, Scott DF, Carter AL. Separation of ornithine and lysine activities of the ornithine transcarbamylase catalyzed reaction . Enzyme . 1983;29:271-277. 24. Brusilow SW, Houser E. Simple method of measurement of orotic acid and orotidine in urine . J Chromatogr . 1989;493:388-391.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Episodic Hyperammonemia in Adult Siblings With Hyperornithinemia, Hyperammonemia, and Homocitrullinuria Syndrome

Loading next page...
 
/lp/american-medical-association/episodic-hyperammonemia-in-adult-siblings-with-hyperornithinemia-P4a0E7ibiq
Publisher
American Medical Association
Copyright
Copyright © 1990 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.1990.00530100104022
Publisher site
See Article on Publisher Site

Abstract

Abstract • A 39-year-old man and his 42-year-old sister, both vegetarians, had episodic confusion for many years, but their mental function was normal between those episodes. They were recently diagnosed with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. Hyperammonemia was documented during an episode of confusion in the male sibling but not in his sister. Both had elevated plasma ornithine, glutamine, and alanine levels and persistently low plasma lysine levels. Homocitrulline was present in their urine, and orotic aciduria and orotidinuria developed in the male sibling following ingestion of allopurinol. Studies on their cultured skin fibroblasts showed deficient metabolism of ornithine, indicating a defect in ornithine transport across the mitochondrial membrane. During therapy with citrulline and phenylbutyrate sodium, plasma ornithine levels increased in both patients, while plasma levels of glutamine and alanine decreased to normal. Since therapy started, their clinical conditions have also improved, and no recurrent neurologic dysfunction has occurred during a follow-up period of 20 months. References 1. Snyderman SE. Clinical aspects of disorders of the urea cycle . Pediatrics . 1981;68:284-289. 2. Batshaw ML, Roan Y, Jung AL, Rosenberg LA, Brusilow SW. Cerebral dysfunction in asymptomatic carriers of ornithine transcarbamylase deficiency . N Engl J Med . 1980;302:482-485.Crossref 3. DiMagno EP, Lowe JE, Snodgrass PJ, Jones JD. Ornithine transcarbamylase deficiency: a cause of bizarre behavior in man . N Engl J Med . 1986;315:744-777.Crossref 4. Granot E, Matoth I, Lotan C, Shvil Y, Lijovetzky G, Yatziv S. Partial carbamyl phosphate synthetase deficiency, simulating Reye's syndrome, in a 9-year-old girl . Isr J Med Sci . 1986;22:463-465. 5. Lezak MD. Neuropsychological Assessment . 2nd ed. New York, NY: Oxford University Press; 1983:422-429, 556-559. 6. Ramnaraine ML, Tuchman M. Aromatic and nitrogen containing acid separation by high performance liquid chromatography and identification by photodiode array detector . J Chromatogr Sci . 1985;24:549-554.Crossref 7. Brusilow SW, Valle DL. Allopurinol (AP) induced orotidinuria (ODNU): a test of heterozygosity for ornithine transcarbamylase (OTC) deficiency . Pediatr Res . 1987;21:189A. Abstract.Crossref 8. Shih VE, Mandell R, Herzfeld A. Defective ornithine metabolism in cultured skin fibroblasts from patients with the syndrome of hyperornithinemia, hyperammonemia, and homocitrullinuria . Clin Chim Acta . 1982;118:149-157.Crossref 9. Shih VE, Efron ML, Moser HW. Hyperornithinemia, hyperammonemia and homocitrullinuria: a new disorder of amino acid metabolism associated with myoclonic seizures and mental retardation . AJDC . 1969;117:83-92. 10. Wright T, Pollitt R. Psychomotor retardation, epileptic and stuporous attacks, irritability and ataxia associated with ammonia intoxication, high blood ornithine levels and increased homocitrulline in the urine . Proc R Soc Med . 1973;66:221. 11. Gatfield PD, Taller E, Wolfe DM, Haust D. Hyperornithinemia, hyperammonemia and homocitrullinuria associated with decreased carbamylphosphate synthetase I activity . Pediatr Res . 1975;9:488-497.Crossref 12. Hommes FA, Ho CK, Roesel RA, Coryell ME, Gordon BA. Decreased transport of ornithine across the inner mitochondrial membrane as a cause of hyperornithinaemia . J Inherited Metab Dis . 1982;5:41-47.Crossref 13. Oyanagi K, Tsuchiyama A, Itakura Y, et al. The mechanism of hyperammonaemia and hyperornithinaemia in the syndrome of hyperornithinaemia, hyperammonaemia with homocitrullinuria . J Inherited Metab Dis . 1983;6:133-134.Crossref 14. Simell O, Mackenzie S, Clow CL, Scriver CR. Ornithine loading did not prevent induced hyperammonemia in a patient with hyperornithinemiahyperammonemia-homocitrullinemia syndrome . Pediatr Res . 1985;19:1283-1287.Crossref 15. Gjessing LR, Lunde HA, Undrum T, Broch H, Alme A, Lie SO. A new patient with hyperornithinaemia, hyperammonaemia and homocitrullinuria treated early with low protein diet . J Inherited Metab Dis . 1986;9:186-192.Crossref 16. Hommes FA, Roesel RA, Metoki K, Hartlage PL, Dyken PR. Studies on a case of HHH syndrome (hyperammonemia, hyperornithinemia, homocitrullinuria) . Neuropediatrics . 1986;17:48-52.Crossref 17. Rodes M, Ribes A, Pineda M, et al. A new family affected by the syndrome of hyperornithinaemia, hyperammonaemia and homocitrullinuria . J Inherited Metab Dis . 1987;10:73-81.Crossref 18. Koike R, Fujimori K, Yuasa T, Miyatake T, Inoue I, Saheki T. Hyperornithinemia, hyperammonemia and homocitrullinuria: case report and biochemical study . Neurology . 1987;37:1813-1815.Crossref 19. Dionsi Vici C, Bachmann C, Gambarara M, Colombo JP, Sabetta G. Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome: low creatine excretion and effect of citrulline, arginine or ornithine supplement . Pediatr Res . 1987;22:364-367.Crossref 20. Nakajima M, Ishii S, Mito T, et al. Clinical, biochemical and ultrastructural study on the pathogenesis of hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome . Brain Dev . 1988;10:181-185.Crossref 21. Valle D, Simell O. The hyperornithinemias . In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic Basis of Inherited Disease . New York, NY: McGraw-Hill International Book Co; 1989:599-627. 22. James MO, Smith RL, Williams RT, Reidenberg M. The conjugation of phenylacetic acid in man, sub-human primates and some nonprimate species . Proc R Soc Lond . 1972;182:25-35.Crossref 23. Hommes FA, Eller AG, Scott DF, Carter AL. Separation of ornithine and lysine activities of the ornithine transcarbamylase catalyzed reaction . Enzyme . 1983;29:271-277. 24. Brusilow SW, Houser E. Simple method of measurement of orotic acid and orotidine in urine . J Chromatogr . 1989;493:388-391.Crossref

Journal

Archives of NeurologyAmerican Medical Association

Published: Oct 1, 1990

References