Nature Medicine | Spoonful of Medicine

The imp of the perverse

The article on Lesch-Nyhan syndrome in this week’s The New Yorker (An Error in the Code) caught my attention. It’s a shame the magazine didn’t publish it online, as it’s worthwhile reading.

Its subtitle is “What can a rare disorder tell us about human behavior?” Not a lot, I’m afraid.

In a nutshell, people with Lesch-Nyhan lack the enzyme HRPT, which is important for purine metabolism. Patients experience damage to their kidneys, joints and other organs. But the most evident feature of the disease is the patients’ drive to inflict physical damage on themselves — what somewhere in the article is referred to as “the imp of the perverse” in reference to a phrase by Edgar Allan Poe.

It won’t come as a surprise that, whereas the kidney and joint damage can be managed in people with the condition, the behavioral problems cannot, at least not very effectively — as Lesch-Nyhan patients tend to bite their fingers and lips off, restraining their hands and removing their teeth are among the most commonly used ways to keep them from doing so.

What can this grim phenotype tell us about human behavior? A scientist who studies the disorder is quoted as saying that “We all do things that are bad for us… Many people bite their fingernails… There are people who chew their lips nervously. Now let’s turn up the volume a little: some people bite their cuticles”. And if you keep on “turning up the volume”, he argues, you end up with people who bite their fingers to the bone. Surely this is an oversimplification. And even if it’s not an oversimplification, it certainly doesn’t go too far towards helping us understand what’s wrong with these patients.

Another thing that captured my attention was the fact that doctors in Japan and France have managed to eliminate self-mutilation in some of these patients by using deep brain stimulation (DBS), a technique that has yet to be approved for this disease in the U.S. Considering the recent report from American scientists of the man who “woke up” as a result of DBS after spending six years in minimally conscious state, I wonder what’s keeping a trial with Lesch-Nyhan patients from starting.

The last thing that caught my attention was the fact that, even though we know what gene is mutated in the disease (HRPT), what part of the brain seems to be affected (the globus pallidus and other parts of the basal ganglia), and what neurotransmitter is reduced (dopamine), there are very few people studying Lesch-Nyhan. During my tenure at Nature Medicine, for example, I don’t recall reading a single submission on this topic. So, for those young scientists who are looking for a niche to get their career started (and for those who are tired of drowning in the swamp of Alzheimer or Parkinson disease), Lesch-Nyhan does not look like a bad possibility at all.


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    Jackie Chamberlain said:

    My foster son has self mutilating behaviors due to a similar congenital disease. UCSF is now providing DBS to children with LN and I am trying to get him evaluated also. At this time, Kaiser wll not approve it. I would love to read more case studies specifically on the DBS for self injurous behaviors

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    Juan Carlos Lopez said:

    Thanks for your post. We at the journal don’t really know much about LNS cases, but surely there have to be support groups on the internet. I would have thought that they would be a good place to hear about other cases of people with the condition.

    Best of luck.

    Juan Carlos Lopez

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    Michelle said:

    To all who this may concern. My oldest son whom has LND just had DBS done on April 3rd. We have yet to turn the stimulators on but he is healing and doing great as of right now.



    Great news on your son. Best of luck. I sincerely wish you the best.