Alternative pathway therapy for urea cycle disorders
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
In man the major pathway for the disposal of waste nitrogen is the urea cycle; in inborn errors of this pathway, nitrogen flux is reduced. As a result there is accumulation of ammonia and glutamine with disordered metabolism of other amino acids. Nitrogen homeostasis can be restored in these patients with a low-protein diet combined with compounds that create alternative pathways for nitrogen excretion. The introduction of these compounds has been a major advance in the management of these inborn errors and as a result the outcome, particularly for those treated early, has improved.
- Bachmann C, Colombo JP (1983) Incrased tryptophan uptake into the brain in hyperammonaemia. Life Sci 33: 2417–2424.
- Bachmann C, Lüthi H, Gradwohl M, Colombo JP (1986) Brain uptake of tryptophan in urease-injected hyperammonaemic rats after treatment with benzoate or hippurate. Biochem Med Metab Biol 36: 214–219.
- Barshop BA, Breuer J, Holm J, Leslie J, Nyhan WL (1989) Excretion of hippuric acid during sodium benzoate therapy in patients with hyperglycinaemia or hyperammonaemia. J Inher Metab Dis 12: 72–79.
- Batshaw ML (1983) Sodium benzoate and arginine: alternative pathway therapy in inborn errors of urea synthesis. Prog Clin Biol Res 127: 69–83.
- Batshaw ML, Brusilow SW (1981) Evidence of lack of toxicity of sodium phenylacetate and sodium benzoate in treating urea cycle enzymopathies. J Inher Metab Dis 4: 231.
- Brusilow SW (1984) Arginine, an indispensable amino acid for patients with inborn errors of urea synthesis. J Clin Invest 74: 2144–2148.
- Brusilow SW (1991) Phenylacetylglutamine may replace urea as a vehicle for waste nitrogen excretion. Pediatr Res 29: 147–150.
- Brusilow SW, Batshaw ML (1979) Arginine treatment of argininosuccinase deficiency. Lancet 1: 124–126.
- 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 Disease, 7th edn. New York: McGraw-Hill, 1187–1232.
- Brusilow SW, Maestri NE (1996) Urea cycle disorders: diagnosis, pathophysiology, and therapy. Adv Pediatr 43: 127–170.
- Brusilow SW, Valle DL, Batshaw M (1979) New pathways of nitrogen excretion in inborn errors of urea synthesis. Lancet 2: 452–454.
- Connelly A, Cross JH, Gadian DG, Hunter JV, Kirkham FJ, Leonard JV (1993) Magnetic resonance spectroscopy shows increased brain glutamine in ornithine carbamoyl transferase deficiency. Pediatr Res 33: 77–81.
- Gregus Z, Fekete T, Varga F, Klaassen CD (1992) Availability of glycine and coenzyme A limits glycine conjugation in vivo. Drug Metab Dispos 20: 234–240
- Griffith AD, Cyr DM, Egan SG, et al (1989) Inhibition of pyruvate carboxylase by sequestration of coenzyme A with sodium benzoate. Arch Biochem Biophys 269: 201–207.
- Hyman SL, Porter CA, Page TJ, Iwata BA, Kissel R, Batshaw ML (1987) Behavior management of feeding disturbances in urea cycle and organic acid disorders. J Pediatr 111: 558–562.
- Kalbag SS, Palekar AG (1988) Soidum benzoate inhibits fatty acids oxidation in rat liver. Effect on ammonia levels. Biochem Metab Biol 40: 133–142.
- Kline JJ, Hug G, Schubert WK, Berry H (1981) Arginine deficiency syndrome. Am J Dis Child 135: 437–442.
- Kubota K, Ishizaki T (1991) Dose-dependent pharmacokinetics of benzoic acid following oral administration of sodium benzoate to humans. Eur J Clin Pharmacol 41: 363–368.
- Kubota K, Ishizaki T (1993) Effect of single oral dose of sodium benzoate on ureagenesis in healthy men and two patients with late onset citrullinaemia. Eur J Clin Pharmacol 45: 465–468.
- Leonard JV (1995) Urea cycle disorders. In Fernandes J, Saudubray JM, Van den Berghe G, eds. Inborn Metabolic Diseases: Diagnosis and Treatment, 2nd ed. Berlin: Springer-Verlag, 167–176.
- Letarte J, Qureshi IA, Ouellet R, Godard M (1985) Chronic benzoate therapy in a boy with partial ornithine transcarbamylase deficiency. J Pediatr 106: 794–797.
- Lewis HB (1914) Studies in the synthesis of hippuric acid in the animal organism. J Biol Chem 18: 225–231.
- Maestri NE, Hauser ER, Bartholomew D, Brusilow SW (1991) Prospective treatment of urea cycle disorders. J Pediatr 119: 923–928.
- Maestri NE, McGowan KD, Brusilow SW (1992) Plasma glutamine concentration: a guide to the management of urea cycle disorders. J Pediatr 121: 259–261.
- Maestri NE, Clissold DB, Brusilow SW (1995) Long-term survival of patients with argininosuccinate synthetase deficiency. J Pediatr 127: 929–935.
- Maestri NE, Brusilow SW, Clissold DB, Bassett SS (1996) Long-term treatment of girls with ornithine transcarbamylase deficiency. N Engl J Med 335: 855–859.
- Michalak A, Lambert MA, Dallaire L, et al (1990) Hypocarnitinemie chez les patients atteints d'un defaut primaire du metabolisme de l'ammoniaque traites avec le benzoate de sodium. Diabete Metab 16: 226–233.
- Msall M, Batshaw ML, Suss R, Brusilow SW, Mellits ED (1984) Neurologic outcome in children with inborn errors of urea synthesis. N Engl J Med 310: 1500–1505.
- O'Connor JE, Costell M, Grisolia S (1987) The potentiation of ammonia toxicity by sodium benzoate is prevented by L-carnitine. Biochem Biophys Res Commun 145: 817–824.
- O'Connor JE, Costell M, Grisolia S (1989) Carbamyl glutamate prevents the potentiation of ammonia toxicity by sodium benzoate. Eur J Pediatr 148: 540–542.
- Ohtani Y, Ohyagani K, Yamamoto S, Matsuda I (1988) Secondary carnitine deficiency in hyperammonemic attacks of ornithine transcarbamylase deficiency. J Pediatr 112: 409–414.
- Palekar AG, Kalbag SS (1991) Amino acids in the rat liver and plasma and some metabolites in the liver after sodium benzoate treatment. Biochem Med Metab Biol 46: 52–58.
- Piscitelli SC, Thibault A, Figg WD, et al (1995) Disposition of phenylbutyrate and its metabolites, phenylacetate and phenylacetylglutamine. J Clin Pharmacol 35: 368–373.
- Ratnakumari L, Qureshi IA, Butterworth RF (1993a) Effect of L-carnitine on cerebral and hepatic energy metabolites in congenitally hyperammonemic sparse-fur mice and its role during benzoate therapy. Metabolism 42: 1039–1046.
- Ratnakumari L, Qureshi IA, Butterworth RF (1993b) Effect of sodium benzoate on cerebral and hepatic energy metabolites in spf mice with congenital hyperammonemia. Biochem Pharmacol 45: 137–146.
- Simell O, Sipila I, Rajantie J, Valle DL, Brusilow SW (1986) Waste nitrogen excretion via amino acid acylation: benzoate and phenylacetate in lysinuric protein intolerance. Pediatr Res 20: 1117–1121.
- Snyderman SE, Boyer A, Holt EL (1959) The arginine requirement of the infant Am J Dis Child 97: 192–195.
- Surtees RJ, Leonard JV (1989) Acute metabolic encephalopathy. J Inher Metab Dis 12(supplement 1): 42–54.
- Takeda E, Kuroda Y, Toshima K, Watanabe T, Naito E, Miyao M (1983) Effect of long term administration of sodium benzoate to a patient with partial ornithine carbamoyl transferase deficiency. Clin Pediatr Phila 22: 206–208.
- Tremblay GC, Qureshi IA (1993) The biochemistry and toxicology of benzoic acid metabolism and its relationship to the elimination of waste nitrogen. Pharmac Ther 60: 63–90.
- Wiech NL, Clissold DM, MacArthur RB (1997) Safety and efficacy of buphenyl (sodium phenylbutyrate) tablets and powder (Abstract). Advances in Inherited Urea Cycle Disorders, Satellite to the 7th International Congress for Inborn Errors of Metabolism, Vienna.
- Wildham K, Koch S, Scheibenreiter S, et al (1992) Long-term follow-up of 12 patients with late onset variant of argininosuccinic acid lysase deficiency: no impairment of intellectual and psychomotor development during therapy. Pediatrics 89: 1182–1184.
- Alternative pathway therapy for urea cycle disorders
Journal of Inherited Metabolic Disease
Volume 21, Issue 1 Supplement, pp 101-111
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers
- Additional Links
- Industry Sectors