A question that I have thought many times, and was also recently asked is, "Why is Glutathione low when Cysteine (a component which makes up Glutathione) is in excess in DS?"
It's a good question. And a hard one at that!
Bottom line - No one really understands it all the way. But, this is what is understood:
There is excess cysteine due to the overexpressed CBS gene. Then there is also the overexpressed SOD1 gene causing a 50% increase in oxidative stress/free radicals. This increase in oxidative stress seems to cause a decrease in Glutathione, as there are not enough antioxidants (Glutathione being one of them) to match the amount of oxidative stress and free radicals which are present.
One of the best studies on the topic is, Homocysteine Metabolism in Children with Down Syndrome: In Vitro Modulation. One quote from the abstract says,
Plasma levels of cystathionine and cysteine were significantly increased, consistent with an increase in CBS activity. Plasma glutathione levels were significantly reduced in the children with DS and may reflect an increase in oxidative stress due to the overexpression of the superoxide dismutase gene, also located on chromosome 21.Another good article on this topic is Steven Fowkes article from CERI, Antioxidant Intervention in Down's Syndrome. This article is a few years old (written in 1998), but it is still interesting.