Familial Hyperlysinemia

Reference work entry

Familial hyperlysinemia is an inborn error of metabolism caused by a defect in the bifunctional protein α-aminoadipic semialdehyde synthase.

Synonyms and Related Disorders

Alpha-aminoadipic semialdehyde synthase deficiency; L-lysine NAD-oxido-reductase deficiency; Lysine:alpha-ketoglutarate reductase deficiency

Genetics/Basic Defects

  1. 1.

    Inheritance: autosomal recessive

  2. 2.
    A heterogeneous group of at least three disorders
    1. a.

      Caused by mutations in the gene (mapped to 7q31.3) encoding α-aminoadipic semialdehyde synthase (AASS), the bifunctional protein that contains both lysine-ketoglutarate reductase (LKR) and saccharopine dehydrogenase (SDH) activity.

    2. b.

      Deficiency in lysine-ketoglutarate reductase (LKR) and/or saccharopine dehydrogenase (SDH) activities leads to a clinical phenotype characterized by hyperlysinemia, lysinuria, and variable saccharopinuria.

    3. c.

      Deficiency in saccharopine oxidoreductase activity, along with deficient LKR and SDH activities, is also observed in...


Genetic Counseling Marfan Syndrome Bifunctional Protein Danlos Syndrome Urinary 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.


  1. Armstrong, M. D., & Robinow, M. (1967). A case of hyperlysinemia: Biochemical and clinical observations. Pediatrics, 39, 546–554.PubMedGoogle Scholar
  2. Carson, N. A. J., Scally, B. G., Neill, D. W., et al. (1968). Saccharopinuria: A new inborn error of lysine metabolism. Nature, 218, 679.PubMedCrossRefGoogle Scholar
  3. Cederbaum, S. D., Shaw, K. N., Dancis, J., et al. (1979). Hyperlysinemia with saccharopinuria due to combined lysine-ketoglutarate reductase and saccharopine dehydrogenase deficiencies presenting as cystinuria. Journal of Pediatrics, 95, 234–238.PubMedCrossRefGoogle Scholar
  4. Cox, R. P. (2001). Errors in lysine metabolism. In C. R. Scriver, A. L. Beaudet, W. S. Sly, & D. Valle (Eds.), The metabolic & molecular bases of inherited disease (8th ed., pp. 1965–1970). New York: McGraw-Hill (Chap. 86).Google Scholar
  5. Dancis, J., Hutzler, J., Ampola, M. G., et al. (1983). The prognosis of hyperlysinemia: An interim report. American Journal of Human Genetics, 35, 438–442.PubMedGoogle Scholar
  6. Dancis, J., Hutzler, J., & Cox, R. P. (1979). Familial hyperlysinemia: Enzyme studies, diagnostic methods, comments on terminology. American Journal of Human Genetics, 31, 290–299.PubMedGoogle Scholar
  7. Dancis, J., Hutzler, J., Cox, R. P., et al. (1969). Familial hyperlysinemia with lysine-ketoglutarate reductase insufficiency. Journal of Clinical Investigation, 48, 1447–1452.PubMedCrossRefGoogle Scholar
  8. Dancis, J., Hutzler, J., Woody, N. C., et al. (1976). Multiple enzyme defects in familial hyperlysinemia. Pediatric Research, 10, 686–691.PubMedGoogle Scholar
  9. Ghadimi, H., Binnington, V. I., & Pecora, P. (1965). Hyperlysinemia associated with retardation. The New England Journal of Medicine, 273, 723–729.PubMedCrossRefGoogle Scholar
  10. Ghadimi, H., Zischka, R., & Binnington, V. I. (1967). Further studies on hyperlysinemia associated with retardation. American Journal of Diseases of Children, 113, 146–151.PubMedGoogle Scholar
  11. Markovitz, P. J., Chuang, D. T., & Cox, R. P. (1984). Familial hyperlysinemias: Purification and characterization of the bifunctional aminoadipic semialdehyde synthase with lysine-ketoglutarate reductase and saccharopine dehydrogenase activities. Journal of Biological Chemistry, 259, 11643–11646.PubMedGoogle Scholar
  12. Özalp, I., Hasanoğlu, A., Tunçbilek, E., et al. (1981). Hyperlysinemia without clinical findings. Acta Paediatrica Scandinavica, 70, 951–953.PubMedCrossRefGoogle Scholar
  13. Sacksteder, K. A., Biery, B. J., Morrell, J. C., et al. (2000). Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia. American Journal of Human Genetics, 66, 1736–1743.PubMedCrossRefGoogle Scholar
  14. Simell, O., Visakarpi, J. K., & Donner, M. (1972). Saccharopinuria. Archives of Disease in Childhood, 47, 52.PubMedCrossRefGoogle Scholar
  15. Smith, T. H., Holland, M. G., & Woody, N. C. (1971). Ocular manifestations of familial hyperlysinemia. Transactions of the American Academy of Ophthalmology & Otolaryngology, 75, 355–360.Google Scholar
  16. Van Gelderen, H. H., & Teijema, H. L. (1973). Hyperlysinemia: Harmless inborn error of metabolism? Archives of Disease in Childhood, 48, 892.PubMedCrossRefGoogle Scholar
  17. Woody, N. C. (1964). Hyperlysinemia. American Journal of Diseases of Children, 108, 543.PubMedGoogle Scholar
  18. Woody, N. C., Hutzler, J., & Dancis, J. (1966). Further studies of hyperlysinemia. American Journal of Diseases of Children, 112, 577–580.PubMedGoogle Scholar
  19. Woody, N. C., & Ong, E. B. (1967). Paths of lysine degradation in patients with hyperlysinemia. Pediatrics, 40, 986–992.PubMedGoogle Scholar
  20. Woody, N. C., & Pupene, M. B. (1970). Excretion of pipecolic acid by infants and by patients with hyperlysinemia. Pediatric Research, 4, 89–95.PubMedCrossRefGoogle Scholar
  21. Woody, N. C., & Pupene, M. B. (1973). Excretion of hypusine by children and by patients with familial hyperlysinemia. Pediatric Research, 7, 994–995.PubMedCrossRefGoogle Scholar
  22. Yiannikas, C., & Cordato, D. (1996). Familial hyperlysinemia in a patient presenting with progressive spastic paraparesis. Neurology, 47, 846.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Personalised recommendations