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Pathogenesis of CNS involvement in disorders of amino and organic acid metabolism
Author(s) -
Kölker S.,
Sauer S. W.,
Hoffmann G. F.,
Müller I.,
Morath M. A.,
Okun J. G.
Publication year - 2008
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-008-0823-z
Subject(s) - pathogenesis , glutaric acid , biology , maple syrup urine disease , disease , blood–brain barrier , medicine , neuroscience , central nervous system , biochemistry , amino acid , immunology , leucine
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.