Abstract
Six inherited disorders of the urea cycle are well described (Fig. 20.1). These are the deficiencies of carbamoyl phosphate synthetase (CPS), ornithine transcarbamoylase (OTC), argininosuccinate synthetase, argininosuccinate lyase, arginase, and N-acetylglutamate synthetase (NAGS). Deficiencies of glutamine synthetase and of citrin have also been described. All these defects are characterised by hyperammonaemia and disordered amino acid metabolism. The presentation is highly variable: those presenting in the newborn period usually have an overwhelming illness that rapidly progresses from poor feeding, vomiting, lethargy or irritability and tachypnoea to fits, coma and respiratory failure. In infancy, the symptoms are less severe and more variable. Poor developmental progress, behavioural problems, hepatomegaly and gastrointestinal symptoms are common. Children and adults frequently have a chronic neurological illness that is characterised by variable behavioural problems, confusion, irritability and episodic vomiting. However, during any metabolic stress the patients may become acutely unwell. Arginase deficiency has more specific symptoms, such as spastic diplegia, dystonia, ataxia and fits. All these disorders have autosomal- recessive inheritance except ornithine transcarbamoylase deficiency, which is X-linked.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Arn PH, Hauser ER, Thomas GH et al (1990) Hyperammonemia in women with a mutation at the ornithine carbamoyltransferase locus. A cause of postpartum coma. N Engl J Med 322:1652–1655
Christodoulou J, Qureshi IA, McInnes RR, Clarke JT (1993) Ornithine transcarbamylase deficiency presenting with strokelike episodes. J Pediatr 122:423–425
Patel JS, Van’t Hoff W, Leonard JV (1994) Arginase deficiency presenting with convulsions. J Inherit Metab Dis 17:254
Häberle J, Gőrg B, Rutsch F et al (2005) Congenital glutamine deficiency with glutamine synthetase mutations. N Engl J Med 353:1926–1933
Saheki T, Kobayashi K, Iijima M et al (2004) Adult-onset type II citrullinaemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle. Mol Genet Metab 81[Suppl 1]:SS20–26
Newsholme EA, Leech AR (1983) Biochemistry for the medical sciences. Wiley, Chichester, pp 491–494
Batshaw ML, Brusilow SW (1978) Asymptomatic hyperammonaemia in low birthweight infants. Pediatr Res 12:221–224
Grünewald S, Fairbanks L, Genet S et al (2004) How reliable is the allopurinol load in detecting carriers for ornithine transcarbamylase deficiency? J Inherit Metab Dis 27:179–186
Hyman SL, Porter CA, Page TJ et al (1987) Behavior management of feeding disturbances in urea cycle and organic acid disorders. J Pediatr 111:558–562
Surtees RJ, Leonard JV (1989) Acute metabolic encephalopathy. J Inherit Metab Dis 12[Suppl 1]:42–54
Connelly A, Cross JH, Gadian DG et al (1993) Magnetic resonance spectroscopy shows increased brain glutamine in ornithine carbamoyl transferase deficiency. Pediatr Res 33:77–81
Caldovic L, Morizono H, Panglao MG et al (2003) Null mutations in the N-acetylglutamate synthase gene associated with acute neonatal disease and hyperammonemia. Hum Genet 112:364–368
Kendall B, Kingsley DPE, Leonard JV, Lingam S, Oberholzer VG (1983) Neurological features and computed tomography of the brain in children with ornithine carbamyl transferase deficiency. J Neurol Neurosurg Psychiatr 46:28–34
Hudak ML, Jones MD, Brusilow SW (1985) Differentiation of transient hyperammonaemia of the newborn and urea cycle enzyme defects by clinical presentation. J Pediatr 107:712–719
Leonard JV (2001) Nutritional treatment of urea cycle disorders. J Pediatr 138[Suppl 1]:S40–44
Brusilow SW, Valle DL, Batshaw ML (1979) New pathways of nitrogen excretion in inborn errors of urea synthesis. Lancet II:452–454
Feillet F, Leonard JV (1998) Alternative pathway therapy for urea cycle disorders. J Inherit Metab Dis 21[Suppl 1]:101–111
Kasumov T, Brunengraber LL, Comte B et al (2004) New secondary metabolites of phenylbutyrate in humans and rats. Drug Metab Dispos 32:10–19
Brusilow SW (1991) Phenylacetylglutamine may replace urea as a vehicle for waste nitrogen excretion. Pediatr Res 29:147–150
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, pp 25
Brusilow SW (1984) Arginine, an indispensible aminoacid for patients with inborn errors of urea synthesis. J Clin Invest 74:2144–2148
Iafolla AK, Gale DS, Roe CR (1990) Citrate therapy in arginosuccinate lyase deficiency. J Pediatr 117:102–105
Bachmann C, Colombo JP, Jaggi K (1982) N-acetylglutamate synthetase (NAGS) deficiency: diagnosis, clinical observations and treatment. Adv Exp Med Biol 153:39–45
Tripp JH, Hargreaves T, Anthony PP et al (1981) Sodium valproate and ornithine carbamyl transferase deficiency (letter). Lancet 1:1165–1166
Maestri NE, McGowan KD, Brusilow SW (1992) Plasma glutamine concentration: a guide to the management of urea cycle disorders. J Pediatr 121:259–261
Dixon MA, Leonard JV (1992) Intercurrent illness in inborn errors of intermediary metabolism. Arch Dis Child 67:1387–1391
Maestri NE, Hauser ER, Bartholomew D, Brusilow SW (1991) Prospective treatment of urea cycle disorders. J Pediatr 119:923–928
Picca S, Dionisi-Vici C, Abeni D et al (2001) Extracorporeal dialysis in neonatal hyperammonaemia: modalities and prognostic indicators. Paediatr Nephrol 16:862–867
Bachmann C (2003) Outcome and survival of 88 patients with urea cycle disorders: a retrospective evaluation. Eur J Pediatr 162:410–416
Todo S, Starzl TE, Tzakis A et al (1992) Orthotopic liver transplantation for urea cycle enzyme deficiency. Hepatology 15:419–422
Saudubray J-M, Touati G, DeLonlay P et al (1999) Liver transplantation in urea cycle disorders. Eur J Pediatr 158[Suppl 2]:S55–59
Sokal E (2006) Transplantation for inborn errors of liver metabolism. J Inherit Metab Dis 29:426–430
General Reference
Tuchman M (2001) Proceedings of a Consensus Conference For the Management of Patients with Urea Cycle disorders. J Pediatr 138[Suppl 1]:S1–S80
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer Medizin Verlag Heidelberg
About this chapter
Cite this chapter
Leonard, J.V. (2006). Disorders of the Urea Cycle and Related Enzymes. In: Fernandes, J., Saudubray, JM., van den Berghe, G., Walter, J.H. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg . https://doi.org/10.1007/978-3-540-28785-8_20
Download citation
DOI: https://doi.org/10.1007/978-3-540-28785-8_20
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-28783-4
Online ISBN: 978-3-540-28785-8
eBook Packages: MedicineMedicine (R0)