Lesch-Nyhan Syndrome: Self-injurious behavior and what it can tell us about identity

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 Lesch-Nyhan Syndrome
Self-injurious behavior and what it can tell us about identity
            Lesch-Nyhan disease is a devastating genetic disorder affecting a very small number of males born each year. Characterized by striking self-injurious behavior, Lesch-Nyhan often results in death during the first two decades of life. However, since its discovery in 1962 by pediatrician and research scientist William L. Nyhan and his student Michael Lesch, studies have led to an in-depth understanding of the disease and myriad treatment plans and potential solutions. Though no cures have been found, a recent article posits that deep brain stimulation could hold the key to further treatment. In the following paragraphs I present basic information on the symptoms, genetics, and potential solutions of Lesch-Nyhan disease, as well as the implications concerning our understanding of the relationship between body, mind, and identity.
Lesch-Nyhan disorder is rooted in a genetic mutation on the long arm of the X chromosome (1). The disease is typically inherited from the mother, but approximately “one third of all cases arise de novo (from new mutations) and do not have a family history” (1). Because the recessive mutation occurs on the X chromosome, the disorder occurs exclusively in males. The site of the mutation codes for the protein hypoxanthine-guanine phosphoribosyltransferase (HGPRT), an enzyme responsible for the metabolism of purines. Lesch-Nyhan patients often lack this protein entirely, resulting in a high concentration of uric acid in the body. This elevated concentration leads to uric acid deposits in the kidneys [kidney stones] and joints [resulting in gout, a condition characterized by acute arthritis and swelling] (2). Lesch-Nyhan patients often exhibit both forms of uric acid build up, but their symptoms transcend typical ailments [kidney stones and gout are common among the general population].
The mutation of the HGPRT gene, often a simple shift of a single nucleotide, results in a drastically different behavioral phenotype. Though a baby boy born with Lesch-Nyhan syndrome seems normal at first, “by the age of three months he has become a so-called floppy baby, and can’t hold up his head or sit up” (3). Beginning around the second year of life (especially when he starts teething), the child will begin to exhibit self-mutilating behaviors (1). He may chew his lips or even try to bite his fingers off. These destructive behaviors will follow the boy throughout his struggle with the disease. Often they are coupled with general dystonia and involuntary facial grimacing (1). The disease will most likely render him incapable of walking, confining him to a wheelchair for life (3). Cognitively, the boy will develop normally. A study conducted by NYU Medical School colleagues Lowell T. Anderson, Monique Ernst, and Susan V. Davis suggests that Lesch-Nyhan patients lead normal emotional lives and exhibit abstract reasoning abilities, concentration levels, and self-awareness levels typical of their age bracket (4).
In an attempt to solve the problem of Lesch-Nyhan, founding doctor William Nyhan began administering allopurinol to his patients, a drug used to cure bouts of gout by lowering uric acid concentrations in the body. Though the drug did result in lower uric acid levels in patients it did not “reduce their self-injurious actions” (3). In other words, “uric acid… was another symptom, and not a cause of the behavior” (3). These findings led to more involved work concerning the origin of the neurobehavioral attributes of a Lesch-Nyhan patient. Neurologists J.E. Visser, P.R. Bar, and H.A. Jinnah published a paper in 2000 suggesting a link between Lesch-Nyhan disease and the basal ganglia, a region of the brain located at the base of the forebrain (6). The basal ganglia has five distinct circuits responsible for “motor, ocular motor, cognitive, personality, and limbic aspects of behavior” (5). Together, these circuits control action selection, or, the process by which the brain decides between several concurrent potential behaviors (6). Studies show that this is accomplished through an inhibitory force the basal ganglia exerts on behavioral circuits. It is thought that “a release of this inhibition permits a motor system to become active” (6). Indeed this process of action selection is severely debilitated by Lesch-Nyhan disease. Recent quantitative MRI studies have indicated that the basal ganglia volumes in Lesch-Nyhan patients are, on average, 34% smaller than age-matched controls (5). Also, patients exhibit significantly lower levels of the neurotransmitter dopamine, a chemical that plays a major role in the function of the basal ganglia (5). Not only does this deficiency adversely affect the functioning of the basal ganglia, it also points to a potentially lower pain threshold among Lesch-Nyhan sufferers, a frightening implication.
Many other studies concerning potential cures and treatments have been carried out in recent years. One particularly hopeful finding is the positive effect of deep brain stimulation, first carried out by Japanese neurosurgeon Takaomi Taira in April, 2000 at the Tokyo Women’s Medical University (3). Originally developed for the treatment of Parkinson’s disease, deep brain stimulation involves the implantation of small electrodes into specific regions of the brain. The electrodes are wired to a generator placed on the patient’s chest. This “generator delivers continuous low-voltage electrical pulses to the brain” via the electrodes (7).  These pulses are effective in stopping the abnormal firing of neurons caused by the low levels of dopamine (7).  After the Tokyo surgery the patient, who before had exhibited severe dystonia and self-mutilation, ceased these destructive behaviors entirely (3). This case provides further evidence for the Lesch-Nyhan link to the basal ganglia [as this region was the target of the deep brain stimulation] and gives hope that Lesch-Nyhan sufferers may one day be able to enjoy safer, more fulfilling lives.
It is now appropriate to examine what Lesch-Nyhan disease can teach us about humanity in general. The first item of interest is the genetic aspect of the syndrome. The human genome is comprised of approximately 20,000 to 25,000 protein-coding genes (8). In Lesch-Nyhan, one of these genes is altered [and only slightly] resulting in a devastating complication of extremely complex behavior. In this way, the disease is a window unto the “mechanics of the genetic code operating on thought and personality” (3). It helps us appreciate how delicate the human body and mind are; it reminds us of our size. It also gives weight to the proposition that DNA is the basis of life. Indeed no other natural compound could single-handedly devastate a human existence in the way that DNA is capable of.
Another pertinent topic of conversation concerns the relationship between body, mind, and the formation of the self. During an episode of self-mutilation, a Lesch-Nyhan patient will be totally aware of what he is doing; he will feel every bit of pain just as a normal person would (3). However, it is imperative to understand that Lesch-Nyhan patients are not masochistic in any way; they do not desire to injure themselves, they merely cannot control their bodies. In his article The Possessed, Richard Preston notes, “they are horrified by the idea of their fingers or lips being severed. They feel as if their hands and mouth don’t belong to them” (3). This bodily estrangement gives us insight into the stuff of identity. If patients exhibit an active self-concept [see reference number 4], if they are aware of their existence, then it could be argued that identity is a function of the mind first and body second. For example, James Elrod, a patient Preston met with during his research, describes his left side as his “devil side” (3). It is apparent that identity does not require continuously functional, “loyal” body parts. In other words, one’s identity may be informed by one’s body [via sensory inputs, etc.], but it is held intact over time by the mind. Identity can “weather the storm” of bodily dysfunction or degeneration. It could be said that the mind is the seat of identity and the body, the vessel with which our identities interact with the world around them.
A final topic is the dysfunction of the basal ganglia and the resulting push to self-mutilate. As discussed above, the malfunction or absence of HPRGT results in a smaller, less effective basal ganglia in Lesch-Nyhan patients. The inhibitory forces of the basal ganglia don’t seem to work. This mechanism of inhibition is of utmost interest; it suggests that the impulse to self-mutilate could be present in all humans, but that healthy            basal ganglias continually restrict the impulse. The aforementioned neurologist H.A. Jinnah posits that the behavioral phenotype of Lesch-Nyhan is comparable to a hyperbolic case of nail-biting; instead of nervously chewing nails a Lesch-Nyhan patient will chew tissue and bone. What does this say about our self-concept? Do we all share a self-injurious perversion? Are we all a gene mutation away from biting our lips off?
            In conclusion, Lesch-Nyhan syndrome is a congenital disorder resulting from a genetic mutation on the X chromosome. This mutation has harrowing effects on both the body and mind of Lesch-Nyhan patients. Sufferers are plagued by acute arthritis, bouts of terrible dystonia, and a vicious push to self-mutilate. Though developments have been made in the understanding of the disease, no cure or accessible treatment is available. In the meanwhile, there is a lot to learn about the human body and mind from Lesch-Nyhan. The neurobehavioral characteristics of the syndrome can tell us a great deal about our own minds and the way in which we come to know ourselves.
 
 
1. “Lesch-Nyhan syndrome.” Wikipedia: The Free Encyclopedia. 26 Sept 2009. 27 Sept 2009. <wikipedia.org>
 
2. “Uric acid.” Wikipedia: The Free Encyclopedia. 22 Sept 2009. 27 Sept 2009. <wikipedia.org>
 
3. Preston, Richard. "The Possessed." New Yorker 13 Aug. 2007: 30-37. Print.
 
4. Anderson, Lowell T., Monique Ernst, and Susan V. Davis. "Cognitive Abilities of Patients with Lesch-Nyhan Disease." Journal of Autism and Developmental Disorders 22.2 (1992): 189-203. Print.
 
5. Visser, J. E., P. R. Bar, and H. A. Jinnah. "Lesch-Nyhan disease and the basal ganglia." Brain Research Reviews 32 (2000): 449-75. Print.
 
6. “Basal ganglia.” Wikipedia: The Free Encyclopedia. 21 Sept 2009. 27 Sept 2009.
 
7. Song, Sora. "How Deep-Brain Stimulation Works." Time 16 July 2006. Print.
 
8. “Human Genome.” Wikipedia: The Free Encyclopedia.

 

Comments

Annette's picture

Trevor

Trevor is a very dear friend of mine who has a severe case of Lesch-Nyhan Syndrome. He is 20 years old and his Mom takes care of him by herself every day. She cannot afford a van to transport Trevor so she has to pick him up and put him in the car everytime they go out. I was wondering if you know of any organixations that would be willing to contribute a generous portion of the cost of a van.....

Paul Grobstein's picture

Lesch-Nyan and issues raised about life

Lots of interesting issues here, including a good illustration of the complexity of the relation between genes and phenotypic characteristics including behavior (see Information on the causes of congenital disorders for another example of the genetic/congential ambiguity).  If the brain is part of the body, then does it make sense to say "the mind is the seat of identity" and the body is something else?  Maybe instead there is a disturbance in what other parts of the body are incorporated into a self by the brain?

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