Effects of arginine treatment on nutrition, growth and urea cycle function in seven Japanese boys with late-onset ornithine transcarbamylase deficiency

Eur J Pediatr. 2006 Sep;165(9):618-24. doi: 10.1007/s00431-006-0143-y. Epub 2006 May 16.


Background: The aim of this study was to investigate the effects of arginine on nutrition, growth and urea cycle function in boys with late-onset ornithine transcarbamylase deficiency (OTCD). Seven Japanese boys with late-onset OTCD enrolled in this study resumed arginine treatment after the cessation of this therapy for a few years. Clinical presentations such as vomiting and unconsciousness, plasma amino acids and urinary orotate excretion were followed chronologically to evaluate urea cycle function and protein synthesis with and without this therapy. In addition to height and body weight, blood levels of proteins, lipids, growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein -3 (IGFBP-3) were monitored.

Results: The frequency of hyperammonemic attacks and urinary orotate excretion decreased significantly following the resumption of arginine treatment. Despite showing no marked change in body weight, height increased gradually. Extremely low plasma arginine increased to normal levels, while plasma glutamine and alanine levels decreased considerably. Except for a slight increase in high-density lipoprotein cholesterol level, blood levels of markers for nutrition did not change. In contrast, low serum IGF-I and IGFBP-3 levels increased to age-matched control levels, and normal urinary GH secretion became greater than the level observed in the controls.

Conclusion: Arginine treatment is able to reduces attacks of hyperammonemia in boys with late-onset OTCD and to increase their growth.

Publication types

  • Clinical Trial

MeSH terms

  • Age of Onset
  • Amino Acids / blood
  • Amino Acids / drug effects
  • Ammonia / blood
  • Analysis of Variance
  • Arginine / blood
  • Arginine / therapeutic use*
  • Biomarkers / blood
  • Biomarkers / urine
  • Blood Proteins / drug effects
  • Blood Proteins / metabolism
  • Body Height / drug effects
  • Body Weight / drug effects
  • Child, Preschool
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Diet, Protein-Restricted
  • Growth / drug effects*
  • Growth Hormone / blood
  • Growth Hormone / drug effects
  • Growth Hormone / urine
  • Humans
  • Hyperammonemia / diet therapy
  • Hyperammonemia / drug therapy
  • Hyperammonemia / etiology
  • Hyperammonemia / metabolism
  • Hyperammonemia / physiopathology
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor Binding Protein 3 / drug effects
  • Insulin-Like Growth Factor I / drug effects
  • Insulin-Like Growth Factor I / metabolism
  • Japan
  • Male
  • Nutritional Physiological Phenomena / drug effects*
  • Ornithine Carbamoyltransferase Deficiency Disease / complications
  • Ornithine Carbamoyltransferase Deficiency Disease / diet therapy
  • Ornithine Carbamoyltransferase Deficiency Disease / drug therapy*
  • Ornithine Carbamoyltransferase Deficiency Disease / metabolism
  • Ornithine Carbamoyltransferase Deficiency Disease / physiopathology*
  • Orotic Acid / urine
  • Thyrotropin / blood
  • Time Factors
  • Treatment Outcome
  • Triglycerides / blood
  • Urea / metabolism*


  • Amino Acids
  • Biomarkers
  • Blood Proteins
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Insulin-Like Growth Factor Binding Protein 3
  • Triglycerides
  • Orotic Acid
  • Insulin-Like Growth Factor I
  • Ammonia
  • Urea
  • Thyrotropin
  • Growth Hormone
  • Arginine