Arginase Deficiency Workup
- Author: Karl S Roth, MD; Chief Editor: Maria Descartes, MD more...
Beyond the inherent problems in diagnosis of any urea cycle disorder, arginase deficiency is somewhat difficult to diagnose.
The typical crisis associated with hyperammonemia is rare, and random measurement of blood ammonia levels during periods of clinical stability is not helpful.
Arginine excretion in urine is not usually massively increased because of isozyme induction; however, a urinary amino acid excretion pattern can be observed. The excretion pattern is similar to that found in cystinuria, with increased arginine, ornithine, lysine, and, possibly, cystine. It can be observed because of competitive inhibition of dibasic amino acid reabsorption by elevated arginine in the renal proximal tubule.
Plasma arginine levels may not be greatly increased in cases of self-restriction of protein intake; therefore, even experienced clinicians may fail to diagnose the disease. Urine orotic acid is usually mildly increased. Plasma ammonia levels may be mildly increased or normal.
When mild-to-moderate elevated plasma arginine levels are observed in association with developmental delay and spasticity, a red cell arginase assay is indicated for definitive biochemical diagnosis.
Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) findings in a relatively large group of patients with arginase deficiency have been reported recently. As in the vast majority of inherited biochemical disorders, and the urea cycle defects specifically, the results are not in any way unique to the disease. Hence, MRI as a part of the initial diagnostic evaluation contributes little, if anything.
Cederbaum SD, Yu H, Grody WW, et al. Arginases I and II: do their functions overlap?. Mol Genet Metab. 2004 Apr. 81 Suppl 1:S38-44. [Medline].
Oldham MS, VanMeter JW, Shattuck KF, Cederbaum SD, Gropman AL. Diffusion tensor imaging in arginase deficiency reveals damage to corticospinal tracts. Pediatr Neurol. 2010 Jan. 42(1):49-52. [Medline].
Ash DE, Scolnick LR, Kanyo ZF, et al. Molecular basis of hyperargininemia: structure-function consequences of mutations in human liver arginase. Mol Genet Metab. 1998 Aug. 64(4):243-9. [Medline].
Scheuerle AE, McVie R, Beaudet AL, Shapira SK. Arginase deficiency presenting as cerebral palsy. Pediatrics. 1993 May. 91(5):995-6. [Medline].
Carvalho DR, Brum JM, Speck-Martins CE, et al. Clinical features and neurologic progression of hyperargininemia. Pediatr Neurol. 2012 Jun. 46(6):369-74. [Medline].
Zhang Y, Landau YE, Miller DT, Marsden D, Berry GT, Kellogg MD. Recurrent unexplained hyperammonemia in an adolescent with arginase deficiency. Clin Biochem. 2012 Dec. 45(18):1583-6. [Medline].
Brosnan ME, Brosnan JT. Orotic acid excretion and arginine metabolism. J Nutr. 2007 Jun. 137(6 Suppl 2):1656S-1661S. [Medline].
Carvalho DR, Farage L, Martins BJ, Brum JM, Speck-Martins CE, Pratesi R. Brain MRI and Magnetic Resonance Spectroscopy Findings in Patients with Hyperargininemia. J Neuroimaging. 2012 Aug 28. [Medline].
Smith W, Diaz GA, Lichter-Konecki U, et al. Ammonia control in children ages 2 months through 5 years with urea cycle disorders: comparison of sodium phenylbutyrate and glycerol phenylbutyrate. J Pediatr. 2013 Jun. 162(6):1228-34, 1234.e1. [Medline].
Berry GT, Steiner RD. Long-term management of patients with urea cycle disorders. J Pediatr. Jan 2001. 138(1 Pt 2):S56-S62. [Medline].
Cederbaum SD, Shaw KN, Valente M. Hyperargininemia. J Pediatr. 1977 Apr. 90(4):569-73. [Medline].
Cowley DM, Bowling FG, McGill JJ, et al. Adult-onset arginase deficiency. J Inherit Metab Dis. 1998 Aug. 21(6):677-8. [Medline].
Crombez EA, Cederbaum SD. Hyperargininemia due to liver arginase deficiency. Mol Genet Metab. 2005 Mar. 84(3):243-51. [Medline].
Haberle J, Koch HG. Genetic approach to prenatal diagnosis in urea cycle defects. Prenat Diagn. 2004 May. 24(5):378-383. [Medline].
Iyer R, Jenkinson CP, Vockley JG, et al. The human arginases and arginase deficiency. J Inherit Metab Dis. 1998. 21 Suppl 1:86-100. [Medline].
Keskinen P, Siitonen A, Salo M. Hereditary urea cycle diseases in Finland. Acta Paediatr. 2008 Oct. 97(10):1412-9. [Medline].
Korman SH, Gutman A, Stemmer E, Kay BS, Ben-Neriah Z, Zeigler M. Prenatal diagnosis fro arginase deficiency by second-trimester fetal erythrocyte arginase assay and first-trimester ARG1 mutation analysis. Prenat Diagn. 2004 Nov. 24(11):857-60. [Medline].
Picker JD, Puga AC, Levy HL, et al. Arginase deficiency with lethal neonatal expression: evidence for the glutamine hypothesis of cerebral edema. J Pediatr. 2003 Mar. 142(3):349-52. [Medline].
Qureshi IA, Letarte J, Ouellet R, Batshaw ML, et al. Treatment of hyperargininemia with sodium benzoate and arginine- restricted diet. J Pediatr. Mar 1984. 104(3):473-6. [Medline].
Saudubray JM, Rabier D. Biomarkers identified in inborn errors for lysine, arginine, and ornithine. J Nutr. 2007 Jun. 137(6 Suppl 2):1669S-1672S. [Medline].
Scaglia F, Lee B. Clinical, biochemical, and molecular spectrum of hyperargininemia due to arginase I deficiency. Am J Med Genet C Semin Med Genet. 2006 May 15. 142(2):113-20. [Medline].
Steiner RD, Cederbaum SD. Laboratory evaluation of urea cycle disorders. J Pediatr. 2001 Jan. 138(1 Suppl):S21-9. [Medline].