Advertisement

Urea Cycle Disorders

  • Kimitoshi NakamuraEmail author
  • Jun Kido
  • Shirou Matsumoto
Chapter

Abstract

A female infant, weighing 2786 g, was born at 39 weeks gestational age with Apgar scores of 8 points at 1 min and 9 points at 5 min after birth. She had no family history of hereditary disorders. Although she had no medical problems at birth and consumed her mother’s breast milk, she developed fever with increased white blood cell counts (WBC: 22,070/μL) and C-reactive protein level (CRP: 1.2 mg/dL) at 2 days after birth. Bacterial infection was suspected, and she received antibiotic therapy. Subsequently, she developed jaundice, convulsions, and respiratory failure and required respiratory support. As the doctors were concerned about a risk of neonatal herpes infection, she received γ-globulin and acyclovir treatments. In addition, she developed mild acidosis and hyperammonemia >400 μg/dL (normal range: 30–80 μg/dL). Urea cycle disorders were suspected, and she was treated with arginine, sodium benzoate, and high glucose infusion. Unfortunately, her plasma ammonia level increased to 2000 μg/dL at 3 days after birth (Fig. 12.1), and she was transferred to a neonatal intensive care unit for treatment with hemodialysis and possible liver transplantation. Her blood ammonia levels gradually improved and normalized at 21 days after birth. Her blood glutamine, glutamic acid, glycine, aspartic acid, citrulline, and arginine levels were 3262 μmol/L (control: 416–740 μmol/L), 265 μmol/L (12–83 μmol/L), 705 μmol/L (140–427 μmol/L), 29 μmol/L (trace–7.2 μmol/L), trace (18–48 μmol/L), and 69 μmol/L (32–150 μmol/L), respectively. The results of the neonatal tandem mass spectrometry screening test for inherited metabolic diseases and analysis test for urinary orotic acid were negative. She was definitively diagnosed with carbamoyl phosphate synthetase 1 deficiency (CPSD) by identification of a mutation of the carbamoyl phosphate synthetase 1 gene (c.2339G>A and c.2945G>A). She underwent a living donor liver transplantation with her father as the donor at the age of 6 months. The subject is presently 7 years and 5 months old, attends primary school, and lives a stable life.

Keywords

Ammonia Amino acids Orotic acid Neonatal onset Late onset 

References

  1. Batshaw ML, Tuchman M, Summar M et al (2014) A longitudinal study of urea cycle disorders. Mol Genet Metab 113:127–130CrossRefGoogle Scholar
  2. Berry GT, Steiner RD (2001) Long-term management of patients with urea cycle disorders. J Pediatr 138:S56–S60CrossRefGoogle Scholar
  3. Brusilow SW (1991) Phenylacetylglutamine may replace urea as a vehicle for waste nitrogen excretion. Pediatr Res 29:147–150CrossRefGoogle Scholar
  4. Brusilow SW, Horwich AL (2001) Urea cycle enzymes. In: Scriver CR, Beaudet AL, Sly WS et al (eds) The metabolic and molecular basis of inherited disease, 8th ed. McGraw-Hill, New York, pp 1909–1963Google Scholar
  5. Brusilow SW, Valle DL, Batshaw M (1979) New pathways of nitrogen excretion in inborn errors of urea synthesis. Lancet 2:452–454CrossRefGoogle Scholar
  6. Kasahara M, Sakamoto S, Shigeta T et al (2010) Living-donor liver transplantation for carbamoyl phosphate synthetase 1 deficiency. Pediatr Transplant 14:1036–1040CrossRefGoogle Scholar
  7. Kido J, Nakamura K, Mitsubuchi H et al (2012) Long-term outcome and intervention of urea cycle disorders in Japan. J Inherit Metab Dis 35:777–785CrossRefGoogle Scholar
  8. Langendonk JG, Roos JC, Angus L et al. (2012) A series of pregnancies in women with inherited metabolic disease. J Inherit Metab Dis 35:419–424Google Scholar
  9. Leonard JV (2001) The nutritional management of urea cycle disorders. J Pediatr 138:S40–S44, discussion S44–S45CrossRefGoogle Scholar
  10. Maestri NE, McGowan KD, Brusilow SW (1992, August) Plasma glutamine concentration: a guide in the management of urea cycle disorders. J Pediatr 121(2):259–261CrossRefGoogle Scholar
  11. Mori M (1991) Urea cycle. In: Journey of nitrogen in the living body (Seitai no tisso no tabi). Kyoritsu Shuppan Co., Ltd., Tokyo, pp 48–49Google Scholar
  12. Morioka D, Kasahara M, Takada Y et al (2005) Current role of liver transplantation for the treatment of urea cycle disorder: a review of the worldwide English literature and 13 cases at Kyoto University. Liver Transpl 11:1332–1342CrossRefGoogle Scholar
  13. Nagata N, Matsuda I, Oyanagi K (1991) Estimated frequency of urea cycle enzymopathies in Japan. Am J Med Genet 39:228–229CrossRefGoogle Scholar
  14. Uchino T, Endo F, Matsuda I (1998) Neurodevelopmental outcome of long-term therapy of urea cycle disorders in Japan. J Inherit Metab Dis 21:S151–S159CrossRefGoogle Scholar
  15. Wakiya T, Sanada Y, Mizuta K et al (2011) Living donor liver transplantation for ornithine transcarbamylase deficiency. Pediatr Transplant 15:390–395CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Kimitoshi Nakamura
    • 1
    Email author
  • Jun Kido
    • 1
  • Shirou Matsumoto
    • 1
  1. 1.Department of PediatricsKumamoto University Graduate School of Medical SciencesKumamotoJapan

Personalised recommendations