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Lysinuric Protein Intolerance

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Summary

In lysinuric protein intolerance (LPI) urinary excretion and clearance of the cationic amino acids lysine, arginine, and ornithine are increased, whereas they are poorly absorbed from the intestine; their plasma concentrations are low. Lysine is an essential amino acid; arginine and ornithine are intermediates in the urea cycle. The transport defect leads to “functional” deficiency of ornithine, the molecular backbone in the urea cycle, and the patients have periods of hyperammonemia. Thus, the clinical symptoms resemble those of patients with urea cycle enzyme deficiences. The patients have periods of nausea and vomiting, and they develop an aversion to protein-rich food, fail to thrive, have hepato- and splenomegaly and osteoporosis, and their growth becomes stunted. The importance of lysine deficiency for the development of the symptoms is unclear. Mental development is normal if periods of prolonged or severe hyperammonemia can be avoided. A potentially lethal complication is interstitial lung disease.

For diagnosis, plasma and urine amino acids, pre- and postprandial blood ammonia and urinary orotic acid are measured. Urea cycle function is tested with an intravenous L-alanine load. The urine contains massive amounts of lysine, arginine, and ornithine; cyst(e)ine excretion may be mildly increased, and mild overflow-aminoaciduria of glutamine, alanine, serine, proline, glycine, and citrulline may occur. Plasma concentrations of cationic amino acids are subnormal or low normal; glutamine, alanine, serine, proline, glycine, and citrulline are moderately elevated. Blood ammonia is normal during fasting but increases after protein meals, as does orotic acid in the urine. Serum lactate dehydrogenase, ferritin, and thyroxin-binding globulin concentrations are elevated.

For maintenance treatment dietary protein in children is restricted to 1.0–1.5 g/kg per day and in adults to 0.5–0.8 g/kg per day, and L-citrulline is supplemented, 2.5–8.5 g daily divided in doses related to the protein content of the meals. The dose is adjusted according to clinical and biochemical response. During a hyperammonemic crisis, protein and amino acids are avoided, glucose administered i. v., and ornithine, arginine, or citrulline i. v. supplemented. Sodium benzoate and sodium phenylacetate may be beneficial.

Over 80 patients have been described or are known to me; 40 are from Finland. The disease is autosomal recessive. The transport protein and the respective genes have not been isolated. Clinical heterogeneity appears minimal, but has not been systematically studied.

Keywords

  • Interstitial Lung Disease
  • Urea Cycle
  • Orotic Acid
  • Blood Ammonia
  • Cationic Amino Acid

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Perheentupa J, Visakorpi JK (1965) Protein intolerance with deficient transport of basic amino acids. Lancet 2: 813

    PubMed  CrossRef  CAS  Google Scholar 

  2. Simell O, Perheentupa J, Rapola J, Visakorpi JK, Eskelin L-E (1975) Lysinuric protein intolerance. Am J Med 59: 229

    PubMed  CrossRef  CAS  Google Scholar 

  3. Rajantie J, Simell O, Rapola J, Perheentupa J (1980) Lysinuric protein intolerance: a two-year trial of dietary supplementation therapy with citrulline and lysine. J Pediatr 97: 927

    PubMed  CrossRef  CAS  Google Scholar 

  4. Silk DBA (1974) Peptide absorption in man. Gut 15: 494

    PubMed  CrossRef  CAS  Google Scholar 

  5. Rajantie J, Simell O, Perheentupa J (1980) Intestinal absorption in lysinuric protein intolerance: impaired for diamino acids, normal for citrulline. Gut 21: 519

    PubMed  CrossRef  CAS  Google Scholar 

  6. Desjeux J-F, Rajantie J, Simell O, Dumontier A-M, Perheentupa J (1980) Lysine fluxes across the jejunal epithelium in lysinuric protein intolerance. J Clin Invest 65: 1382

    PubMed  CrossRef  CAS  Google Scholar 

  7. Rajantie J, Simell O, Perheentupa J (1980) Basolateral membrane transport defect for lysine in lysinuric protein intolerance. Lancet 1: 1219

    PubMed  CrossRef  CAS  Google Scholar 

  8. Rajantie J, Simell O, Perheentupa J (1981) Lysinuric protein intolerance. Basolateral transport defect in renal tubuli. J Clin Invest 67: 1078

    Google Scholar 

  9. Smith DW, Scriver CR, Tenenhouse HS, Simell 0 (1987) Lysinuric protein intolerance mutation is expressed in the plasma membrane of cultured skin fibroblasts. Proc Natl Acad Sci USA 84: 7711

    CAS  Google Scholar 

  10. Carpenter TO, Levy HL, Holtrop ME, Shih VE, Anast CS (1985) Lysinuric protein intolerance presenting as childhood osteoporosis. Clinical and skeletal response to citrulline therapy. N Engl J Med 312: 290

    Google Scholar 

  11. Rajantie J, Simell O, Perheentupa J, Siimes M (1980) Changes in peripheral blood cells and serum ferritin in lysinuric protein intolerance. Acta Paediatr Scand 69: 741

    PubMed  CrossRef  CAS  Google Scholar 

  12. Awrich AE, Stackhouse J, Cantrell JE, Patterson JH, Rudman D (1975) Hyperdibasicaminoaciduria, hyperammonemia, and growth retardation: treatment with arginine, lysine and citrulline. J Pediatr 87: 731

    PubMed  CrossRef  CAS  Google Scholar 

  13. Rajantie J, Simell O, Perheentupa J (1983) Oral administration of c-N-acetyllysine and homocitrulline for lysinuric protein intolerance. J Pediatr. 102: 388

    PubMed  CrossRef  CAS  Google Scholar 

  14. Friedman M, Gumbmann MR (1981) Bioavailability of some lysine derivatives in mice. J Nutr 111: 1362

    PubMed  CAS  Google Scholar 

  15. Simell O, McKenzie S, Clow CL, Scriver CR (1985) Ornithine loading did not prevent induced hyperammonemia in a patient with HHH syndrome. Pediatr Res 19: 1283

    PubMed  CrossRef  CAS  Google Scholar 

  16. Brusilow S, Tinker J, Batshaw ML (1980) Amino acid acylation: a mechanism of nitrogen excretion in inborn errors of urea synthesis. Science 207: 659–611

    PubMed  CrossRef  CAS  Google Scholar 

  17. Brusilow SW, Danney M, Waber U, Batshaw M, Burton B et al (1984) Treatment of episodic hyperammonemia in children with inborn errors of urea synthesis. N Engl J Med 310: 1630

    PubMed  CrossRef  CAS  Google Scholar 

  18. Whelan DT, Scriver CR (1968) Hyperdibasicaminoaciduria: an inherited disorder of amino acid transport. Pediatr Res 2: 525

    PubMed  CrossRef  CAS  Google Scholar 

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© 1990 Springer-Verlag Berlin Heidelberg

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Simell, O. (1990). Lysinuric Protein Intolerance. In: Fernandes, J., Saudubray, JM., Tada, K. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-02613-7_44

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  • DOI: https://doi.org/10.1007/978-3-662-02613-7_44

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