Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1981 May;33(3):345–353.

Autosomal recessive inheritance of human mitochondrial carbamyl phosphate synthetase deficiency.

J W McReynolds, B Crowley, M J Mahoney, L E Rosenberg
PMCID: PMC1685048  PMID: 7246541

Abstract

The mode of inheritance of hepatic mitochondrial carbamyl phosphate synthetase (CPS I) deficiency has not been established conclusively in the past. In this study, hepatic tissue obtained by percutaneous biopsy from all members of the immediate family of two girls affected with partial CPS I deficiency was assayed for CPS I, ornithine transcarbamylase (OTC), and arginase activities. Only values for CPS I activity differed significantly from those in controls. The two affected girls each had markedly reduced CPS I activities of about 6% of the control mean. Their brother had activity well within the normal range. Of greatest significance was the finding that both parents had activities below the 95% confidence limits in controls, and intermediate between the deficient values of the two girls and the control range. The father and mother had, respectively, 32% and 54% of mean control activity. These data indicate that CPS I deficiency is inherited as an autosomal recessive trait and that the two affected girls are homozygous for the mutant gene, their brother is homozygous for the normal allele, and the parents are heterozygous.

Full text

PDF
345

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ADACHI T., TANIMURA A., ASAHINA M. A COLORIMETRIC DETERMINATION OF OROTIC ACID. J Vitaminol (Kyoto) 1963 Sep 10;9:217–226. doi: 10.5925/jnsv1954.9.217. [DOI] [PubMed] [Google Scholar]
  2. Arashima S., Matsuda I. A case of carbamyl phosphate synthetase deficiency. Tohoku J Exp Med. 1972 Jun;107(2):143–147. doi: 10.1620/tjem.107.143. [DOI] [PubMed] [Google Scholar]
  3. BROWN G. W., Jr, COHEN P. P. Comparative biochemistry of urea synthesis. I. Methods for the quantitative assay of urea cycle enzymes in liver. J Biol Chem. 1959 Jul;234(7):1769–1774. [PubMed] [Google Scholar]
  4. Batshaw M., Brusilow S., Walser M. Treatment of carbamyl phosphate synthetase deficiency with keto analogues of essential amino acids. N Engl J Med. 1975 May 22;292(21):1085–1090. doi: 10.1056/NEJM197505222922101. [DOI] [PubMed] [Google Scholar]
  5. Brown T., Hug G., Bove K., Brown H., Lansky L. Letter: Reye's syndrome. Lancet. 1974 Sep 21;2(7882):716–717. doi: 10.1016/s0140-6736(74)93289-9. [DOI] [PubMed] [Google Scholar]
  6. Clarke S. A major polypeptide component of rat liver mitochondria: carbamyl phosphate synthetase. J Biol Chem. 1976 Feb 25;251(4):950–961. [PubMed] [Google Scholar]
  7. DeMars R., LeVan S. L., Trend B. L., Russell L. B. Abnormal ornithine carbamoyltransferase in mice having the sparse-fur mutation. Proc Natl Acad Sci U S A. 1976 May;73(5):1693–1697. doi: 10.1073/pnas.73.5.1693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Farriaux J. P., Ponte C., Pollitt R. J., Lequien P., Formstecher P., Dhondt J. L. Carbamyl-phosphate-synthetase deficiency with neonatal onset of symptoms. Acta Paediatr Scand. 1977 Jul;66(4):529–534. doi: 10.1111/j.1651-2227.1977.tb07940.x. [DOI] [PubMed] [Google Scholar]
  9. Gatfield P. D., Taller E., Wolfe D. M., Haust M. D. Hyperornithinemia, hyperammonemia, and homocitrullinuria associated with decreased carbamyl phosphate synthetase I activity. Pediatr Res. 1975 May;9(5):488–497. doi: 10.1203/00006450-197505000-00006. [DOI] [PubMed] [Google Scholar]
  10. Gelehrter T. D., Snodgrass P. J. Lethal neonatal deficiency of carbamyl phosphate synthetase. N Engl J Med. 1974 Feb 21;290(8):430–433. doi: 10.1056/NEJM197402212900804. [DOI] [PubMed] [Google Scholar]
  11. Hommes F. A., De Groot C. J., Wilmink C. W., Jonxis J. H. Carbamylphosphate synthetase deficiency in an infant with severe cerebral damage. Arch Dis Child. 1969 Dec;44(238):688–693. doi: 10.1136/adc.44.238.688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  13. Lambotte C., Adam A., Van Der Hofstadt J., Dodinval-Versie J., Gielen J. Severe neonatal deficiency of carbamylphosphate synthetase. Acta Paediatr Belg. 1977 Jul-Sep;30(3):151–155. [PubMed] [Google Scholar]
  14. Maier K. P., Talke H., Gerok W. Letter: Hepatic biopsy technics and enzymatic activity. N Engl J Med. 1976 Aug 26;295(9):508–509. doi: 10.1056/NEJM197608262950919. [DOI] [PubMed] [Google Scholar]
  15. Mantagos S., Tsagaraki S., Burgess E. A., Oberholzer V., Palmer T., Sacks J., Baibas S., Valaes T. Neonatal hyperammonaemia with complete absence of liver carbamyl phosphate synthetase activity. Arch Dis Child. 1978 Mar;53(3):230–234. doi: 10.1136/adc.53.3.230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McReynolds J. W., Mantagos S., Brusilow S., Rosenberg L. E. Treatment of complete ornithine transcarbamylase deficiency with nitrogen-free analogues of essential amino acids. J Pediatr. 1978 Sep;93(3):421–427. doi: 10.1016/s0022-3476(78)81149-4. [DOI] [PubMed] [Google Scholar]
  17. Odievre M., Charpentier C., Cathelineau L., Vedrenne J., Delacoux des Roseaux F., Mercie C. Hyperammoniémie constitutionnelle avec déficit en carbamyl-phosphate-synthétase. Evolution sous régime dietétique. Arch Fr Pediatr. 1973 Jan;30(1):5–13. [PubMed] [Google Scholar]
  18. Ricciuti F. C., Gelehrter T. D., Rosenberg L. E. X-chromosome inactivation in human liver: confirmation of X-linkage of ornithine transcarbamylase. Am J Hum Genet. 1976 Jul;28(4):332–338. [PMC free article] [PubMed] [Google Scholar]
  19. SELIGSON D., HIRAHARA K. The measurement of ammonia in whole blood, erythrocytes, and plasma. J Lab Clin Med. 1957 Jun;49(6):962–974. [PubMed] [Google Scholar]
  20. Sheffield L. J., Danks D. M., Hammond J. W., Hoogenraad N. J. Massive pulmonary hemorrhage as a presenting feature in congenital hyperammonemia. J Pediatr. 1976 Mar;88(3):450–452. doi: 10.1016/s0022-3476(76)80263-6. [DOI] [PubMed] [Google Scholar]
  21. Short E. M., Conn H. O., Snodgrass P. J., Campbell A. G., Rosenberg L. E. Evidence for x-linked dominant inheritance of ornithine transcarbamylase deficiency. N Engl J Med. 1973 Jan 4;288(1):7–12. doi: 10.1056/NEJM197301042880102. [DOI] [PubMed] [Google Scholar]
  22. Sinatra F., Yoshida T., Applebaum M., Masion Hoogenraad N. J., Sunshine P. Abnormalities of carbamyl phosphate synthetase and ornithine transcarbamylase in liver of patients with Reye's syndrome. Pediatr Res. 1975 Nov;9(11):829–833. doi: 10.1203/00006450-197511000-00005. [DOI] [PubMed] [Google Scholar]
  23. Wilson R. G., Masters P. L. Neonatal death due to carbamyl phosphate synthetase deficiency. Aust Paediatr J. 1977 Jun;13(2):119–121. doi: 10.1111/j.1440-1754.1977.tb01136.x. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES