Abstract
Lysinuric protein intolerance (LPI; MIM 222700) is an inherited aminoaciduria with an autosomal recessive mode of inheritance. Biochemically, affected patients present with increased excretion of the cationic amino acids: lysine, arginine, and ornithine. We report the first case of LPI diagnosed in Malaysia presented with excessive excretion of homocitrulline. The patient was a 4-year-old male who presented with delayed milestones, recurrent diarrhea, and severe failure to thrive. He developed hyperammonemic coma following a forced protein-rich diet. Plasma amino acid analysis showed increased glutamine, alanine, and citrulline but decreased lysine, arginine and ornithine. Urine amino acids showed a marked excretion of lysine and ornithine together with a large peak of unknown metabolite which was subsequently identified as homocitrulline by tandem mass spectrometry. Molecular analysis confirmed a previously unreported homozygous mutation at exon 1 (235 G > A, p.Gly79Arg) in the SLC7A7 gene. This report demonstrates a novel mutation in the SLC7A7 gene in this rare inborn error of diamino acid metabolism. It also highlights the importance of early and efficient treatment of infections and dehydration in these patients. Conclusion: The diagnosis of LPI is usually not suspected by clinical findings alone, and specific laboratory investigations and molecular analysis are important to get a definitive diagnosis.
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Acknowledgements
We thank the Director General of Health Malaysia for the permission to publish this paper. Our special thanks to Dr. Shahnaz Murad, Director of Institute for Medical Research Kuala Lumpur, and Dr. Rohani Md Yasin, Head of Specialised Diagnostic Centre, for the critical reading of the manuscript and valuable comments. We wish to acknowledge the expert technical assistance of Professor Johannes Häberle and Miss Dana Leiteritz from the Division of Metabolism, University Children’s Hospital and University of Zurich, Switzerland in the molecular diagnosis of the proband. This case study was funded by a diagnostic fund from the Ministry of Health where most of the authors work (except the author from Australia).
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Habib, A., Md Yunus, Z., Azize, N.A. et al. Hyperexcretion of homocitrulline in a Malaysian patient with lysinuric protein intolerance. Eur J Pediatr 172, 1277–1281 (2013). https://doi.org/10.1007/s00431-013-1947-1
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DOI: https://doi.org/10.1007/s00431-013-1947-1