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News from Science Daily Oct. 11,
2007
New Insight Into Childhood Metabolic
Disease
Glutaric acidemia type I (GA-I) is an inherited disorder
similar to Huntington disease. Individuals with GA-I are unable to
breakdown completely the amino acids lysine and tryptophan and the
intermediates of lysine and tryptophan breakdown accumulate in the
brain
In most, but not all, affected children, a period of normal
development is followed by an irreversible brain injury triggered by
a nonspecific illness. If children with GA-I reach 5 years of age
without suffering brain injury they usually never show symptoms of
the disease.
New research using a mouse model of GA-I (Gcdh--/-- mice) by William
Zinnanti and colleagues at Penn State, Hershey, has provided insight
into the mechanisms underlying injury and age-dependent
susceptibility to the disease and suggested a way to monitor
children with the disease.
Gcdh--/-- mice do not develop disease if lysine and tryptophan are
excluded from their diet. Exposure to lysine in the diet caused
brain damage in both young and adult mice, but the extent of the
damage was much greater in the young mice.
This was shown to be because lysine uptake is enhanced in the
immature brain compared with the adult brain and so more
intermediates of lysine degradation accumulated, thereby increasing
the susceptibility to brain damage.
Treating young Gcdh--/-- mice with homoarginine, to limit brain
uptake of lysine, and glucose, to limit lysine degradation,
substantially decreased brain damage caused by exposure to lysine in
the diet.
Furthermore, brain injury was preceded by decreases in glutamate and
GABA in the brain that could be monitored by proton nuclear magnetic
resonance spectroscopy, providing hope that a way of monitoring
children with GA-I to predict the onset of brain injury might be
developed.
Article: Mechanism of age-dependent susceptibility and novel
treatment strategy in glutaric acidemia type I
Note: This story has been adapted from material provided by Journal
of Clinical Investigation.
From:
http://www.sciencedaily.com/releases/2007/10/071011180857.htm
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