Amino Acids

, Volume 47, Issue 9, pp 1751–1762 | Cite as

Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature

  • A. SchluneEmail author
  • S. vom Dahl
  • D. Häussinger
  • R. Ensenauer
  • E. Mayatepek
Review Article
Part of the following topical collections:
  1. Homoarginine, Arginine and Relatives


Hyperargininemia is caused by deficiency of arginase 1, which catalyzes the hydrolysis of l-arginine to urea as the final enzyme in the urea cycle. In contrast to other urea cycle defects, arginase 1 deficiency usually does not cause catastrophic neonatal hyperammonemia but rather presents with progressive neurological symptoms including seizures and spastic paraplegia in the first years of life and hepatic pathology, such as neonatal cholestasis, acute liver failure, or liver fibrosis. Some patients have developed hepatocellular carcinoma. A usually mild or moderate hyperammonemia may occur at any age. The pathogenesis of arginase I deficiency is yet not fully understood. However, the accumulation of l-arginine and the resulting abnormalities in the metabolism of guanidine compounds and nitric oxide have been proposed to play a major pathophysiological role. This article provides an update on the first patients ever described, gives an overview of the distinct clinical characteristics, biochemical as well as genetical background and discusses treatment options.


Urea cycle Arginase deficiency Hyperargininemia Guanidino compounds Oxidative stress 



l-Arginine-glycine amidinotransferase


Argininosuccinate lyase


Argininosuccinate synthase


Cerebrospinal fluid


Carbamoyl phosphate synthase I






Guanidino compounds


N-Acetyl-glutamate synthase


Nitric oxide


Nitric oxide synthase


Magnetic resonance imaging


Magnetic resonance spectroscopy


Mitochondrial ornithine transporter


Ornithine aminotransferase


Ornithine transcarbamylase


Urea cycle disorder


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.


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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • A. Schlune
    • 1
    Email author
  • S. vom Dahl
    • 2
  • D. Häussinger
    • 2
  • R. Ensenauer
    • 1
  • E. Mayatepek
    • 1
  1. 1.Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s HospitalHeinrich Heine UniversityDüsseldorfGermany
  2. 2.Department of Gastroenterology, Hepatology and Infectious Diseases, University HospitalHeinrich Heine UniversityDüsseldorfGermany

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