More on the "I": Lesch - Nyhan Disease and Choice

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Biology 202
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More on the "I": Lesch - Nyhan Disease and Choice

Jessica Zaldivar

These last few weeks of class we have been discussing the role of the "I" function in terms of sight, dreaming and choice. Many interesting points were raised about why the "I" function exists and what its role is in controlling behavior and regulating choice. My last paper touched on some of these ideas when looking at obsessive compulsive disorder and the role of the "I" (5). I would like to return to some of these ideas with the more extreme and complex example of the self mutilation experienced by sufferers of Lesch - Nyhan disease.

In one class meeting discussing sleep, a student jokingly discounted the theory that one sleeps when bored by saying that if people could choose to sleep they wouldn't because it is a waste of time so therefore sleep must be a necessary function outside the control of the "I". This statements helped me to clarify my own thoughts on the "I" function. There are many behaviors that are outside the control of the "I" because they are necessary functions such as sleep and breathing and heartbeat and digestion. It is true, as one member of class mentioned, that this is good because it does not "clutter" the brain nor does the "I" have to "waste" time regulating these things; but I think it is a larger matter than that.

As a sociology major I am interested in the way people behave and interact in society. This class has also allowed me to see the way that people interact with themselves and their nervous systems as another sort of social activity. Many of our activities are regulated by society. From birth we internalize certain norms and values that tell us how to behave in certain situations. If these are broken we feel guilt or shame which manifest themselves through the nervous system with sweaty palms, increased heartbeat, depression, etc. So in a way our reposes, even on the level of neurons, is effected by our society. The "I" function plays a very important role in this because it can "tell" the self what is and is not appropriate and it can help to regulate behavior. So there is a strong connection between the "I" and the nervous system, but both have to have some autonomy. The nervous system has to be able to carry out necessary functions inspite of the "I" and the "I" also needs some autonomy from the nervous system. In our discussions of REM sleep and dreaming it seemed to me that the "I" gained autonomy through sleep. In dreams the "I" is able to free itself from the nervous system and physical reality and the nervous system allows this by paralyzing itself. Disorders such as Obsessive Compulsive [OCD] and Lesch - Nyhan [LND] are examples of the breakdown of communication between the "I" and the nervous system. Due to chemical or genetic abnormalities the nervous system causes the body to do things that are against the wants of the "I". While obsessive compulsive disorder is caused by stresses and a chemical imbalance in the brain that can be treated by therapy and drugs, Lesch- Nyhan is caused by a genetic defect that causes certain chemical imbalances and cannot be successfully treated although there have been some studies done with genetic manipulation that have been successful to some degree. The only answer for patients with Lesch- Nyhan is to be restrained - this is something I will return to later in the paper.

Lesch - Nyhan disease was discovered in 1967 by Michael Lesch M.D and William Nyhan M.D. Ph.D. (1). It was the first known psychiatric abnormality caused by a specific enzyme defect and first demonstrated that a genetic defect could cause a specific behavior (3). Lesch - Nyhan disease is caused by a defect on the X chromosome that can be inherited or can occur by mutation. It is a recessive gene so it predominately affect males and occurs in about 1 out of every 380,000 births (1). This genetic defect causes an error in the purine (3).metabolism that causes an absence of hypoxanthine guanine phosphoribosyl transferate (HGPRTase) which leads to excessive production of uric acid (2).The excess uric acid forms urate crystals which are deposited in the kidneys, joints, nervous system and in other tissue which causes symptoms such as impaired kidney function, joint pain, self mutilation, muscle weakness, neurological impairment, spacticity, and speech impairment (1) (2).The most distinctive and disturbing symptom is compulsive self-mutilation which will be the larger focus of this paper.

Children with Lesch - Nyhan begin self mutilating by the age of three to six months and as they grow more physically capable and more cognitively able to think of ways to mutilate, the mutilation escalates. The most common forms are lip biting, finger biting, head/limb banging and eye gouging. According to the Matheny School and Hospital web site, no one knows exactly what causes this self - mutilation but it is hypothesized that is caused by neurotransmitter abnormalities that affect the metabolism of seratonin and dopamine (1).More specifically it leads to lessened levels of dopamine in the caudate and putamine parts of the brain. This is something that we have run across before in looking at many other behavioral disorders including Obsessive Compulsive Disorder, depression and schizophrenia. Another hypothesis put forward by The National Institute for Neurological Disorders and Stroke suggest that it is the buildup of uric acid itself that causes the self - mutilation (4).

There have been some experiments done with cloning and manipulating the gene that cause Lesch - Nyhan but so far there is no successful treatment. Treatment overall is symptomatic and includes restraints, allopurinal for the control of excess uric acid, and drugs to treat some of the stress and neurological symptoms (1) (2). (4). The Matheny School and Hospital specializes in treating patients with this disease and educating parents and teachers about it. The advocate for the development of safe, comfortable, enabling restraints to be used to control the self - mutilation that is characteristic to this disease (1). The argue that while restraints are traditionally seen to be confining and disabling, for patients with Lesch - Nyhan restraints are enabling because they "reduce the stress and fear of self injury and allow the individual to concentrate on constructive activity" (1). People who do not need to be restrained at all times can be trained to request them when they feel the need to inflict harm on themselves.

Another interesting aspect of this disease is what they call "indirect/emotional self injury" where the sufferer intentionally and compulsively injures others in order to receive punishment or to feel guilty (1). These episodes are followed by profuse apologies but a repetition of the behavior. In order to handle this they teach parents and caregivers "selective ignoring" which is a response to compulsive outward aggression. This method teaches them to not react at all to the disturbing behavior and not to give the patient the satisfaction of anger or guilt. In one very interesting and extreme case they tell about a boy who very much enjoyed movies but could not resist the compulsion to turn down an invitation so that he could deny himself the pleasure of going (1). Here again we see something similar to what I found with Obsessive Compulsive Disorder, people with both diseases are aware that they suffer from them and do not want to carry out t he destructive activity be it washing or self injury. Patients with Lesch - Nyhan want to be restrained and can feel great stress if they are not restrained or if they do not trust their care givers to stop them from hurting themselves(1). It seems as though, possibly through defects in chemical receptors that affect specificity for serotonin and dopamine, that there is a breakdown in communication between the nervous system and the "I".

To look at this problem I will return to a quote I used in my last paper by Dr. Schwartz from UCLA: "The beauty of being human and not a rat or a monkey is that you don't have to listen to your brain every single time" To look at this problem I will return to a quote I used in my last paper by Dr. Schwartz from UCLA: "The beauty of being human and not a rat or a monkey is that you don't have to listen to your brain every single time" (6). But it seems that in the case of genetic disorders the body does have to listen to the brain every time, even in spite of the "I". In sufferers of OCD it was possible to train them not to succumb to their compulsions by using behavioral modification therapy and drugs, but for sufferers of Lesch - Nyhan it is not possible to teach them to stop the mutilating behaviors - it is only possible to teach them to recognize the signs and learn to restrain themselves. It seems that because Lesch - Nyhan is a genetic disorder it is not possible to correct the symptoms of it just by allowing the "I" to recognize the behavior and stop it. In this case the "I" is fully aware but cannot modify the nervous system from within the same way it can with OCD. This suggests that while the "I" has limited control over the nervous system down to functioning of the neurons themselves, the "I" cannot modify behavior that is due to a genetic condition. Similarly, it is interesting to note that this genetic disorder has no effect on the development of the "I". Sufferers of LND have a clear sense of self, personality and appropriate behavior as internalized from society they know that they do not want to mutilate themselves or to hurt others but they are incapable of controlling this due to defect in the nervous system. In this case the "I" and the nervous system are disassociated from each other. So while it seems necessary for the nervous system and the "I" to have some autonomy it is disastrous if the delicate balance between then is disturbed. This also suggests that the "I" is not located entirely within the nervous system because if it were it would not be so disassociated from behavior and its development would have been impaired by the disruptions in the nervous system.

 

For further reading:

I was first introduced to Lesch - Nyhan disease and given the idea for this paper through reading "The Evening and the Morning and the Night" by Octavia Butler. It can be found in her short story anthology Blood Child and I highly recommend it for anyone who is interested in neurobiology and science fiction. She comes up with some pretty interesting concepts.

 

Further Reading

Butler, Octavia. "The Evening and the Morning and the Night." Blood Child New York: Seven Stories Press, 1996.

WWW Resources

1) Matheny School and Hospital

2) National Organization for Rare Disorders

3) The Purine Research Society

4) The National Institute for Neurological Disorders and Stroke

5) My Paper on Obsessive Compulsive Disorder

6) All about Obsessive Compulsive Disorder , - scroll down to "Shake in the Mind"

 

 

Comments made prior to 2007

Hi, I was reading your website about Lesch-Nyhan, and noticed that you have us (the Purine Research Society) listed as a website reference. Our server has recently gone belly-up, and we had to change URLs. Our new address is www.PurineResearchSociety.org
The http://www2.dgsys.com/~purine/ website is no longer available. You might want to make that change. Thanks so much ... Tahma Metz, 18 November 2004

Comments

Amy Laws's picture

Parent of LND child

As a parent of an 11 year old son with LND, your paper is very interesting. I was wondering if you are currently conducting any research on this matter to help find treatment or a cure. I don't think you really touched on the fact that these kids are all in wheelchairs as well, which emphasises the impact the disease has over their motor skills and the amount of control it requires them to have to make the simplest movements. My son was first diagnosed with mitochondrial disease, which also seems to be a counterpart to the LND, I've been told. This may be another avenue of interest for you to research and write about.

sarah's picture

uric acid treatment

Good afternoon. I have been conducting an in depth research on uric acid treatment. My brother is a sufferer and it breaks my heart to see him evoked in so much pain each time the symptoms flares up. Unfortunately, I havent' been able to find any permanent cure to this issue yet. But there are some foods and prevention that can help. One of which is to avoid foods with purines at all costs because purines encourages the body to build up uric acid which flares up the disease.

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