Journal of Applied Genetics

, Volume 48, Issue 3, pp 277–280 | Cite as

First reported case of lysinuric protein intolerance (LPI) in Lithuania, confirmed biochemically and by DNA analysis

  • Loreta Cimbalistienè
  • Willy Lehnert
  • Kirsi Huoponen
  • Vaidutis Kučinskas
Case Report

Abstract

We report on an 18-year-old Lithuanian girl with hepatosplenomegaly noticed at birth, which progressed thereafter. The patient had to wait about 17 years for an accurate diagnosis and appropriate therapy. Lactase deficiency, congenital cataract of the right eye, and osteoporosis were observed. Episodes of drowsiness were caused by intake of high-protein food. Laboratory findings included slight hyperammonaemia, high plasma Citr, Ala, Gly, Glu, Ser levels, as well as citrullinuria, lysinuria, glutaminuria, alaninuria, argininuria, prolinuria, hydroxyprolinuria, ornithinuria, and orotic aciduria. A version to high-protein diet strongly suggested a disorder resulting in hyperammonaemia. Citrullinaemia was suspected. Subsequently the diagnosis of LPI was made on the basis of biochemical and clinical features. Molecular genetic testing revealed a mutation in theSLC7A7 gene, confirming the diagnosis.

Keywords

aversion to protein hepatosplenomegaly lysinuric protein intolerance secondary juvenile osteoporosis 

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References

  1. Borsani G, Bassi MT, Sperandeo MP, De Grandi A, Buoninconti A, Riboni M, et al. 1999.SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance. Nat Genet 21: 297–301.CrossRefPubMedGoogle Scholar
  2. Borsani G, et al. 2000. Structure of theSLC7A7 gene and mutational analysis of patients affected by lysinuric protein intolerance. Am J Hum Genet 66: 92–99.CrossRefPubMedGoogle Scholar
  3. Desjeux J-F, Rajantie J, Simell 0, Dumontier A-M, Perheentupa J, 1980. Lysine fluxes across the jejunal epithelium in lysinuric protein intolerance. J Clin Invest 65: 1382–1387.CrossRefPubMedGoogle Scholar
  4. Incerti B, Andria G, Parenti G, Sebastio G, Ghezzi M, Strisciugho P, Sperli D, 1993. Lysinuric protein intolerance: studies on 17 Italian patients. Am J Hum Genet Suppl 53: 908.Google Scholar
  5. Kato T, Mizutani N, Ban M, 1984. Hyperammonemia in lysinuric protein intolerance. Pediatrics 73: 489–492.PubMedGoogle Scholar
  6. Lauteala T, Sistonen P, Savontaus ML, Mykkanen J, Simell J, Lukkarinen M, Aula P, 1997. Lysinuric Protein Intolerance (LPI) gene maps to the long arm of chromosome 14. Am J Hum Genet 60: 1479–1486.CrossRefPubMedGoogle Scholar
  7. Lukkarinen M, Nanto-Salonen K, Pulkki K, Aalto M, Simell O, 2003. Oral supplementation corrects plasma lysine concentrations in lysinuric protein intolerance. Metabolism 52: 935–938.CrossRefPubMedGoogle Scholar
  8. Mannuci L, Emma F, Maeket M, Bachmas C, Boulat O, Carozzo R, Rizzoni G, Dionisi-Vici, 2005. Increased NO production in lysinuric protein intolerance. J Inherited Metab Dis 28: 123–129.CrossRefGoogle Scholar
  9. Norio R, Visakorpi JK, 1965. Protein intolerance with deficient transport of basic amino acids. Lancet 2: 813.Google Scholar
  10. Norio R, Perheentupa J, Kekomaki M, Visakorpi JK, 1971. Lysinuric protein intolerance: an autosomal recessive disease. Clin Genet 2: 214.CrossRefPubMedGoogle Scholar
  11. Parenti G, Sebastio G, Strisciuglio P, Incerti B, Pecoraro C, Terracciano L, Andria G, 1995. Lysinuric protein intolerance characterized by bone marrow abnormalities and severe clinical course. J Pediatr 126: 246–251.CrossRefPubMedGoogle Scholar
  12. Perheentupa J, Visakorpi JK, 1965. Protein intolerance with deficient transport of basic amino acids: another inborn error of metabolism. Lancet 2: 813–816.CrossRefPubMedGoogle Scholar
  13. Palacin M, Borsani G, Sebastio G, 2001. The molecular bases of cystinuria and lysinuric protein intolerance. Curr Opin Genet Dev 11: 328–335.CrossRefPubMedGoogle Scholar
  14. Puomila K, Simell O, Huoponen K, Mykkanen J, 2006. Two alternative promoters regulate the expression of lysinuric protein intolerance geneSLC7A7. Mol Genet Metab: 28.Google Scholar
  15. Rajantie J, Simell O, Perheentupa J, 1980. Basolateralmembrane transport defect for lysine in lysinuric protein intolerance. Lancet 1: 1219.CrossRefPubMedGoogle Scholar
  16. Rajantie J, Simell O, Perheentupa J, 1981. Basolateral-membrane transport defect for lysinuric protein intolerance. J Clin Invest 67: 1078–1082.CrossRefPubMedGoogle Scholar
  17. Rajantie J, Simell O, Perheentupa J, 1983. Oral administration of n-acetyllysine and homocitrulline in lysinuric protein intolerance. J Pediatr 102: 388–390.CrossRefPubMedGoogle Scholar
  18. Santamaria F, Parenti G, Guidi G, Rotondo A, Grillo G, Larocca MR, et al. 1996. Early detection of lung involvement in lysinuric protein intolerance: role of high-resolution computed tomography and radioisotopic methods. Am J Respir Crit Care Med 153: 731–735.PubMedGoogle Scholar
  19. Simell O, 2001. Lysinuric protein intolerance and other cationic aminoacidurias. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease, 8th ed. New York, McGraw-Hill Medical Publication Division 3: 4933–4956.Google Scholar
  20. Shoji Y, Noguchi A, Shoji Y, Matsumori M, Takasago Y, Takayanagi M, et al. 2002. Five novel SLC7A7 variants and y+L gene-expression pattern in cultured lymphoblasts from Japanese patients with lysinuric protein intolerance. Hum Mutat 20: 375–381.CrossRefPubMedGoogle Scholar
  21. Sperandeo MP, Bassi MT, Riboni M, Parenti G, Buoninconti A, Manzoni M, et al. 2000. Structure of theSLC7A7 gene and mutation analysis of patients affected by lysinuric protein intolerance. Am J Hum Genet 66: 92–99.CrossRefPubMedGoogle Scholar
  22. Sperandeo MP, Annunziata P, Ammendola V, Fiorito V, Pepe A, Soldovieri MV, et al. 2005. Lysinuric protein intolerance: identification and functional analysis of mutations of theSLC7A7 gene. Hum Mutat 25: 410.CrossRefPubMedGoogle Scholar
  23. Tanner LM, Nanto-Salonen K, Niinikovski H, Huoponen K, Simell O, 2007. Long-term oral lysine supplementation in lysinuric protein intolerance. Metabolism 56: 185–189.CrossRefPubMedGoogle Scholar
  24. Torrents D, Mykkanen J, Pineda M, Feliubadalo L, Estevez R, de Cid R, et al. 1999. Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene. Nat Genet 21: 293–296.CrossRefPubMedGoogle Scholar

Copyright information

© Institute of Plant Genetics, Polish Academy of Sciences, Poznan 2007

Authors and Affiliations

  • Loreta Cimbalistienè
    • 1
  • Willy Lehnert
    • 2
  • Kirsi Huoponen
    • 3
  • Vaidutis Kučinskas
    • 1
  1. 1.Department of Human and Medical GeneticsVilnius UniversityVilniusLithuania
  2. 2.Metabolic UnitUniversity Children’s HospitalFreiburgGermany
  3. 3.Department of Medical GeneticsUniversity of TurkuFinland

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