Journal of Inherited Metabolic Disease

, Volume 29, Issue 5, pp 612–619

Infant mice with glutaric acidaemia type I have increased vulnerability to 3-nitropropionic acid toxicity

Authors

    • Department PsychiatryUniversity of Colorado Health Sciences Center
  • L. S. Crnic
    • Department PediatricsUniversity of Colorado Health Sciences Center
  • S. I. Goodman
    • Department PediatricsUniversity of Colorado Health Sciences Center
  • C. R. Freed
    • Department Medicine and Division of Clinical PharmacologyUniversity of Colorado Health Sciences Center
Original Article

DOI: 10.1007/s10545-006-0102-9

Cite this article as:
Bjugstad, K.B., Crnic, L.S., Goodman, S.I. et al. J Inherit Metab Dis (2006) 29: 612. doi:10.1007/s10545-006-0102-9

Summary

Glutaric acidaemia type I (GA I) is an inborn error of metabolism caused by a deficiency of glutaryl-CoA dehydrogenase (GCDH) and is characterized clinically by striatal degeneration that almost always occurs in early childhood. A murine knockout model of GA I has the organic aciduria seen in the human disorder, but this model does not develop striatal degeneration spontaneously. 3-Nitropropionic acid (3NP), a succinic dehydrogenase inhibitor with specificity for the striatum, was investigated as a potential initiator of striatal degeneration in GCDH-deficient mice. This study shows that GCDH-deficient mouse pups are more susceptible to 3NP than their wild-type littermates, and that all mouse pups are more sensitive to 3NP as infants than as adolescents and adults. Increased sensitivity to 3NP early in life may model the developmental window for the striatal damage observed in human GA I.

Abbreviations

3HGA

3-hydroxyglutaric acid

3NP

3-nitropropionic acid

GA I

glutaric acidaemia type I

GA

glutaric acid

GCDH

glutaryl-CoA dehydrogenase

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© SSIEM and Springer 2006