Effects of arginine treatment on nutrition, growth and urea cycle function in seven Japanese boys with late-onset ornithine transcarbamylase deficiency
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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.
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.
Arginine treatment is able to reduces attacks of hyperammonemia in boys with late-onset OTCD and to increase their growth.
KeywordsArginine deficiency Growth hormone Nutrition and growth Plasma glutamine and alanine Ornithine transcarbamylase deficiency Orotate
Free fatty acids
Insulin-like growth factor-I
Insulin-like growth factor binding protein-3
Ornithine transcarbamylase deficiency
Total ketone body
- 6.Brusilow SW, Horwich AL (2001) Urea cycle enzymes. In: Scriver CR, Baudet AL, Valle D, Sly WS. The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, New-York, pp 1909–1964Google Scholar
- 14.Gianotti L, Maccario M, Lanfranco F, Ramunni J, Di Vito L, Grottoli S, Muller EE, Chigo E, Arvat E (2000) Arginine counteracts the inhibitory effect of recombinant human insulin-like growth factor I on the somatotroph responsiveness to growth hormone-releasing hormone in humans. J Clin Endocrinol Metab 85:3604–3608PubMedCrossRefGoogle Scholar
- 15.Gianotti L, Pincelli AI, Scacchi M, Rolla M, Bellitti D, Arvat E, Lanfranco F, Torsello A, Ghigo E, Cavagnini F, Muller EE (2000) Effects of recombinant human insulin-like growth factor I administration on spontaneous and growth hormone (GH)-releasing hormone-stimulated GH secretion in anorexia nervosa. J Clin Endocrinol Metab 85:2805–2809PubMedCrossRefGoogle Scholar
- 25.Nagasaka H, Komatsu H, Ohura T, Sogo T, Inui A, Yorifuji T, Kei Murayama, Masaki Takayanagi, Hideaki Kikuta, Kunihiko Kobayashi (2004) Nitric oxide synthesis in ornithine transcarbamylase deficiency: possible involvement of low NO synthesis in clinical manifestations of urea cycle defect. J Pediatr 145:259–262PubMedCrossRefGoogle Scholar
- 29.Widhalm K, Koch S, Scheibenreiter S, Knoll E, Colombo JP, Bachmann C, Thalhammer O (1992) Long-term follow-up of 12 patients with the late-onset variant of arginisuccinic acid lyase deficiency: no impairment of intellectual and psychomotor development during therapy. Pediatrics 89:1182–1184PubMedGoogle Scholar