Carbamyl phosphate synthetase deficiency

Diagnosis of CPS or OTC deficiency may not be apparent from the blood aminogram. Ornithine levels typically are normal. The presence of hyperammonemia, hyperglu-taminemia, hyperalaninemia and orotic aciduria in a critically ill infant affords presumptive evidence for OTC deficiency. The presence of this blood aminogram without orotic aciduria suggests carbamyl phosphate synthetase deficiency. 

Carbamyl phosphate synthetase deficiency. Carbamyl phosphate synthetase deficiency is rare. Neonates quickly develop lethargy, hypothermia, vomiting and irritability. The hyperammonemia typically is severe, even exceeding 1 mmol/1. Occasional patients with a partial enzyme deficiency have had a relapsing syndrome of lethargy and irritability upon exposure to protein. Brain damage can occur in both neonatal and late-onset groups. 

Tuchman M, Mauer SM, Holzknecht RA, Summar ML, Vnencak-Jones CL. Prospective versus clinical diagnosis and therapy of acute neonatal hyperam-monaemia in two sisters with carbamyl phosphate synthetase deficiency. J Inher Metab Dis 1992 15 269-77. 

None of these cases can be considered as established examples of an isolated carbamyl phosphate synthetase deficiency. Although in the first the clinical history and the presence of severe hyperammonemia support the diagnosis of a defect of urea synthesis, the normal finding of levels of plasma amino acids, apart from glycine, is against it. No actual numerical data on the level of activity of the urea cycle enzymes are given. 

H4. Hommes, F. A., Degroot, C. J., Wilmink, C. W., and Jonxis, J. H. P., Carbamyl phosphate synthetase deficiency in an infant with severe cerebral damage. Arch. Dis. Childhood 44, 688-693 (1969). 

Kotani Y, et al. Carbamyl phosphate synthetase deficiency and postpartum hyperammonemia. Am J Obstet Gynecol. 2010 203(l) el0-l. 

Propionyl CoA inhibits A(-acetylglutamate synthetase competitively with respect to acetyl CoA, forming A(-propionylglutamate and reducing the synthesis of A(-acetylglutamate. This is an obligatory activator of carbamyl phosphate synthetase, the first enzyme of urea synthesis. Vitamin B12 deficiency may result in some degree of protein intolerance and hyperammonemia. 

Call G, Seay AR, Sherry R, Qureshi lA. Clinical features of carbamyl phosphate synthetase-I deficiency in an adult. Ann Neurol 1984 16 90-3. 

Hoshide R, Matsuura T, Haraguchi Y, Endo F, Yoshinaga M, Matsuda I. Carbamyl phosphate synthetase I deficiency-one base substitution in an exon of the CPSI gene causes a 9-basepair deletion due to aberrant splicing. J Clin Invest 1993 91 1884-7. 

Lo WD, Sloan HR, Sotos JF, Klinger RJ. Late clinical presentation of partial carbamyl phosphate synthetase I deficiency Am J Dis Child 1993 147 267-9. 

Sassaman EA, Zartler AS, Mulick JA. Cognitive functioning in two sisters with carbamyl phosphate synthetase I deficiency, f Ped Psychol 1981 6 171-5. 

Zimmer KP, Naim HY, Koch HG, Golombo JP, Rossi R, Schmid KW, et al. Survival after early treatment for carbamyl phosphate synthetase (CPS) I deficiency associated with increase of intramitochondrial CPS I. Lancet 1995 346 1530-1. 

No proved example of a gross deficiency solely of carbamyl phosphate synthetase (Fig. 12) has as yet been recorded. Prior to the characterization and separation of the two carbamyl phosphate synthetases, it... 

It may be concluded therefore that a metabolic disorder due solely to a deficiency of carbamyl phosphate synthetase has not yet been proved. 

Association of Carbamyl Phosphate Synthetase with Ornithine Transcarbamylase Deficiency... 

It may be concluded that in many cases of an ornithine transcarbamylase deficiency, there is an associated carbamyl phosphate deficiency, usually of moderate degree. It is because of this that it has even been suggested (E2) that hyperammonemia might not be due solely to ornithine transcarbamylase deficiency. This view cannot be correct in at least two cases where the carbamyl phosphate synthetase was within the normal, albeit low normal, range. 

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