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Growth Hormone Deficiency and Lysinuric Protein Intolerance: Case Report and Review of the Literature

  • Research Report
  • Chapter
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JIMD Reports, Volume 19

Part of the book series: JIMD Reports ((JIMD,volume 19))

Abstract

Background: Lysinuric protein intolerance (LPI; MIM# 222700) is a rare metabolic disorder caused by a defective cationic amino acids (CAA) membrane transport leading to decreased circulating plasma CAA levels and resulting in dysfunction of the urea cycle. Short stature is commonly observed in children with LPI and has been associated with protein malnutrition. A correlation between LPI and growth hormone deficiency (GHD) has also been postulated because of the known interaction between the AA arginine, ornithine, and lysine and growth hormone (GH) secretion. Our report describes a case of GHD in an LPI patient, who has not presented a significant increase in growth velocity with recombinant-human GH (rhGH) therapy, suggesting some possible pathogenic mechanisms of growth failure.

Case Presentation: The proband was a 6-year-old boy, diagnosed as suffering from LPI, erythrophagocytosis (HP) in bone marrow, and short stature. Two GH provocative tests revealed GHD. The patient started rhGH therapy and a controlled-protein diet initially with supplementation of oral arginine and then of citrulline. At 3-year follow-up, no significant increase in growth velocity and in insulin-like growth factor-1 (IGF-1) levels was observed. Inadequate nutrition and low plasmatic levels of arginine, ornithine, lysine, and HP may have contributed to his poor growth.

Conclusion: Our case suggests that growth failure in patients with GHD and LPI treated with rhGH could have a complex and multifactorial pathogenesis. Persistently low plasmatic levels of lysine, arginine, and ornithine, associated with dietary protein and caloric restriction and systemic inflammation, could determine a defect in coupling GH to IGF-1 production explaining why GH replacement therapy is not able to significantly improve growth impairment. We hypothesize that a better understanding of growth failure pathophysiology in these patients could lead to the development of more rational strategies to treat short stature in patients with LPI.

Competing interests: None declared

An erratum to this chapter is available at 10.1007/8904_2014_362

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Abbreviations

AA:

Amino acids

CAA:

Cationic amino acids

GH:

Growth hormone

GHD:

Growth hormone deficiency

HP:

Erythrophagocytosis

IGF-1:

Insulin-like growth factor-1

IUGR:

Intrauterine growth restriction

LDH:

Lactic dehydrogenase

LPI:

Lysinuric protein intolerance

MPH:

Midparental height

NO:

Nitric oxide

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Acknowledgements

The Authors are grateful to CEINGE Laboratories of University of Naples Federico II (Italy) for testing SLC7A7 gene, and to Alice Dianin for dietetic assessment of the patient to Ms. Judyth Dillon for editing the English version of the manuscript.

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Authors and Affiliations

  1. Department of Life Sciences and Reproduction Sciences, Pediatric Clinic, “Giambattista Rossi” Hospital, University of Verona, Verona, Italy

    Maines Evelina, Morandi Grazia, Olivieri Francesca, Camilot Marta, Cavarzere Paolo, Gaudino Rossella, Antoniazzi Franco & Bordugo Andrea

Authors
  1. Maines Evelina
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  2. Morandi Grazia
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  3. Olivieri Francesca
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  4. Camilot Marta
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  6. Gaudino Rossella
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  7. Antoniazzi Franco
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Corresponding author

Correspondence to Maines Evelina .

Editor information

Editors and Affiliations

  1. Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria

    Johannes Zschocke

  2. Division for Metabolic Diseases, University Children´s Hospital, Zürich, Switzerland

    Matthias Baumgartner

  3. Tulane University Medical School, New Orleans, Louisiana, USA

    Eva Morava

  4. Division of Child and Adolescent Neurolo, Mayo Clinic, Rochester, USA

    Marc Patterson

  5. Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, United Kingdom

    Shamima Rahman

  6. Centre for Child and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

    Verena Peters

Additional information

Communicated by: Jean-Marie Saudubray

Appendices

Conflict of Interest

Maines Evelina, Morandi Grazia, Olivieri Francesca, Camilot Marta, Cavarzere Paolo, Gaudino Rossella, Antoniazzi Franco, and Andrea Bordugo declare that they have no conflict of interest.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000.

Written informed consent was obtained from the parents of the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Animal Rights

This article does not contain any studies with human or animal subjects performed by the any of the authors.

Author’s Contributions

Dr. Gaudino and Dr. Cavarzere conceived and designed the study and ensured the accuracy of the data and analysis. Dr. Olivieri collected the data and revised the manuscript critically for important intellectual content. Dr. Maines and Dr. Morandi ensured the accuracy of the data and analysis, wrote the initial draft, and critically revised the manuscript for important intellectual content. Dr. Camilot ensured the accuracy of the draft and edited the English version of the manuscript. Dr. Antoniazzi conceived and designed the study, ensured the accuracy of the data analysis, and critically revised the manuscript for important intellectual content. Dr. Bordugo revised the manuscript critically for important intellectual content.

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Evelina, M. et al. (2014). Growth Hormone Deficiency and Lysinuric Protein Intolerance: Case Report and Review of the Literature. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 19. JIMD Reports, vol 19. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_362

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  • DOI: https://doi.org/10.1007/8904_2014_362

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  • Print ISBN: 978-3-662-46189-1

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