Journal of Inherited Metabolic Disease

, Volume 31, Issue 2, pp 194–204

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

DOI: 10.1007/s10545-008-0823-z

Cite this article as:
Kölker, S., Sauer, S.W., Hoffmann, G.F. et al. J Inherit Metab Dis (2008) 31: 194. doi:10.1007/s10545-008-0823-z

Summary

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.

Abbreviations

CD

Canavan–van Bogaert–Bertrand disease

CNS

central nervous system

GA I

glutaric aciduria type I

IEM

inborn error of metabolism

LNAA

large neutral amino acid

NAA

N-acetyl-l-aspartate

OAD

organic aciduria

PKU

phenylketonuria

SSADH

succinic semialdehyde dehydrogenase

TCA cycle

tricarboxylic acid cycle

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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