Diagnostic Value of Orotic Acid Excretion in Heritable Disorders of the Urea Cycle and in Hyperammonemia Due to Organic Acidurias

Overview

Journal Eur J Pediatr

Specialty Pediatrics

Date 1980 Aug 1

PMID 7439194

Citations 19

Authors

C Bachmann

J P COLOMBO

Affiliations

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Abstract

Orotic acid excretion in urine in increased in ornithine transcarbamylase deficiency, citrullinemia and argininemia; it is barely increased in argininosuccinic aciduria and normal in carbamylphosphate synthetase deficiency and in hyperammonemia due to organic aciduria. The determination of orotic acid excretion is useful in differentiating the cases of hyperammonemia and reduces the need for enzymatic assays on tissue biopsies for decisions on therapy. The data indicate that orotic acid does not merely reflect ammonia concentration in plasma, but depends on carbamylphosphate concentration. Arginine could play a key role in the regulation of ammonia detoxication.

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References

Krieger I, Bachmann C, GRONEMEYER W, cejka J . Propionic acidemia and hyperlysinemia in a case with ornithine transcarbamylase (OTC) deficiency. J Clin Endocrinol Metab. 1976; 43(4):796-802. DOI: 10.1210/jcem-43-4-796. View

Shigesada K, TATIBANA M . Enzymatic synthesis of acetylglutamate by mammalian liver preparations and its stimulation by arginine. Biochem Biophys Res Commun. 1971; 44(5):1117-24. DOI: 10.1016/s0006-291x(71)80201-2. View

Batshaw M, BRUSILOW S, Walser M . Treatment of carbamyl phosphate synthetase deficiency with keto analogues of essential amino acids. N Engl J Med. 1975; 292(21):1085-90. DOI: 10.1056/NEJM197505222922101. View

Short E, CONN H, SNODGRASS P, Campbell A, ROSENBERG L . Evidence for x-linked dominant inheritance of ornithine transcarbamylase deficiency. N Engl J Med. 1973; 288(1):7-12. DOI: 10.1056/NEJM197301042880102. View

Snyderman S, Sansaricq C, Chen W, NORTON P, PHANSALKAR S . Argininemia. J Pediatr. 1977; 90(4):563-8. DOI: 10.1016/s0022-3476(77)80367-3. View

Levin B . Hereditary metabolic disorders of the urea cycle. Adv Clin Chem. 1971; 14:65-143. DOI: 10.1016/s0065-2423(08)60145-6. View

COLOMBO J, Peheim E, Flury W . Comparison of plasma creatinine determined with the Greiner Selective Analyser GSA II and the glomerular filtration rate. Clin Biochem. 1980; 13(1):6-11. DOI: 10.1016/s0009-9120(80)90422-1. View

Brusilow S, Valle D, Batshaw M . New pathways of nitrogen excretion in inborn errors of urea synthesis. Lancet. 1979; 2(8140):452-4. DOI: 10.1016/s0140-6736(79)91503-4. View

Goldstein A, Hoogenraad N, Johnson J, Fukanaga K, SWIERCZEWSKI E, Cann H . Metabolic and genetic studies of a family with ornithine transcarbamylase deficiency. Pediatr Res. 1974; 8(1):5-12. DOI: 10.1203/00006450-197401000-00002. View

10.

Wick H, Bachmann C, Baumgartner R, BRECHBUHLER T, COLOMBO J, Wiesmann U . Variants of citrullinaemia. Arch Dis Child. 1973; 48(8):636-41. PMC: 1648609. DOI: 10.1136/adc.48.8.636. View

11.

Russell A, Levin B, Oberholzer V, Sinclair L . Hyperammonaemia. A new instance of an inborn enzymatic defect of the biosynthesis of urea. Lancet. 1962; 2(7258):699-700. DOI: 10.1016/s0140-6736(62)90508-1. View

12.

Ricciuti F, Gelehrter T, ROSENBERG L . X-chromosome inactivation in human liver: confirmation of X-linkage of ornithine transcarbamylase. Am J Hum Genet. 1976; 28(4):332-8. PMC: 1685051. View

13.

Kuchel P, Roberts D, Nichol L . The simulation of the urea cycle: correlation of effects due to inborn errors in the catalytic properties of the enzymes with clinical-biochemical observations. Aust J Exp Biol Med Sci. 1977; 55(3):309-26. DOI: 10.1038/icb.1977.26. View

14.

Cathelineau L, Petit F, Coude F, Kamoun P . Effect of propionate and pyruvate on citrulline synthesis and ATP content in rat liver mitochondria. Biochem Biophys Res Commun. 1979; 90(1):327-32. DOI: 10.1016/0006-291x(79)91628-0. View

15.

Dhondt J, Farriaux J . [Detection of female carriers of ornithine-carbamyl-transferase deficiency by measurement of orotic acid in the urine]. Lille Med. 1975; 20(8):727-30. View

16.

BROWN Jr G, Cohen P . Comparative biochemistry of urea synthesis. I. Methods for the quantitative assay of urea cycle enzymes in liver. J Biol Chem. 1959; 234(7):1769-74. View

17.

Bachmann C, COLOMBO J, Beruter J . Short chain fatty acids in plasma and brain: quantitative determination by gas chromatography. Clin Chim Acta. 1979; 92(2):153-9. DOI: 10.1016/0009-8981(79)90109-8. View