There is wonderful, disturbing, and extremely graphic article in last week’s New Yorker (not online) about Lesch-Nyhan syndrome, a mysterious disorder characterized by excessive amounts of uric acid and a dangerous tendency to injure oneself. In its bleakest incarnation, Lesch-Nyhan turns victims into their own worst enemy, as their can’t help but chew off their lower lip, or bite of their own fingers, or curse at a loved one. (For Lesch-Nyhan patients, aggression and hateful speech are a sign of love.)
What biological mistake could cause such a tragic behavioral disorder? The problem results from a minor stretch of DNA (only 657 base pairs long), which codes for HPRT, an enzyme that helps recycle DNA inside cells. Nobody knows how this glitch leads to such self-destructive tendencies, but reduced levels of dopamine seem to be implicated. According to one study, Lesch-Nyhan brains contain eighty-percent less dopamine than normal brains in the basal ganglia.
But here’s what so odd: Parkinson’s patients also have drastically reduced dopamine levels in the basal ganglia, a result of the death of dopamine neurons. And yet, as Richard Preston notes, Lesch-Nyhan manifests itself as a very different set of symptoms:
In some ways, Lesch-Nyhan syndrome looks like Parkinson’s disease reversed. People with Parkinson’s have trouble starting physical actions, and are said to hypokinetic. Lesch-Nyhan people start actions too easily, and can’t stop an action once it starts; they are said to be hyperkinetic. Because Parkinson’s is also associated with a deficiency of dopamine in the basal ganglia, scientists have looked to each disease for clues to the other.
Diseases like Lesch-Nyhan are a bleak reminder of how much remains to be learned about the brain. We know so little, and understand even less.
Read the whole article. It’s another Richard Preston gem.