Journal of Inherited Metabolic Disease

, Volume 31, Issue 2, pp 194–204 | Cite as

Pathogenesis of CNS involvement in disorders of amino and organic acid metabolism

  • S. Kölker
  • S. W. Sauer
  • G. F. Hoffmann
  • I. Müller
  • M. A. Morath
  • J. G. Okun
SSIEM Symposium 2007


Inherited disorders of amino and organic acid metabolism have a high cumulative frequency, and despite heterogeneous aetiology and varying clinical presentation, the manifestation of neurological disease is common. It has been demonstrated for some of these diseases that accumulating pathological metabolites are directly involved in the manifestation of neurological disease. Various pathomechanisms have been suggested in different in vitro and in vivo models including an impairment of brain energy metabolism, an imbalance of excitatory and inhibitory neurotransmission, altered transport across the blood–brain barrier and between glial cells and neurons, impairment of myelination and disturbed neuronal efflux of metabolic water. This review summarizes recent knowledge on pathomechanisms involved in phenylketonuria, glutaric aciduria type I, succinic semialdehyde dehydrogenase deficiency and aspartoacylase deficiency with examples, highlighting general as well as disease-specific concepts and their putative impact on treatment.


GABAB Receptor Large Neutral Amino Acid Glutaric Aciduria Type Canavan Disease Organic Aciduria 
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.



Canavan–van Bogaert–Bertrand disease


central nervous system


glutaric aciduria type I


inborn error of metabolism


large neutral amino acid




organic aciduria




succinic semialdehyde dehydrogenase

TCA cycle

tricarboxylic acid cycle


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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • S. Kölker
    • 1
  • S. W. Sauer
    • 1
  • G. F. Hoffmann
    • 1
  • I. Müller
    • 1
  • M. A. Morath
    • 1
  • J. G. Okun
    • 1
  1. 1.Department of General Pediatrics, Division of Inherited Metabolic DiseaseUniversity Children’s Hospital HeidelbergHeidelbergGermany

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