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At what age are Lesch-Nyhan
symptoms first noticed?
Babies as young as one week old can have "orange
sand" in the diapers. This is a symptom of accumulation of uric acid leading
to secretion of urinary urate. By three months of age developmental problems
become noticeable. The first sign is usually a "limp baby" unable to lift
his head. By six months the parents may notice an unusual arching of the
back. At nine months they are unable to pull themselves into a standing
position and do not crawl. At twelve months they are not walking and by
eighteen months they evidence involuntary movements that seem jerky and
twisting and have odd posturing of the arms and legs and torso.
What age does self-injury begin?
Self-injury can begin as young as two years of age.
Self-injury can start as late as 10 or 12 years of age. Some boys with
Lesch-Nyhan disease never become self-injurious. In general, the younger
the age of onset of self-injury, the more severe the self-injury eventually
becomes.
What causes Lesch-Nyhan disease?
Lesch-Nyhan disease is caused by a genetic mutation
on the X chromosome. The mutation results in an absence of the enzyme
hypoxanthine phosphoribosyltransferase (HPRT).
Why do only boys have the disease?
The gene is recessive and occurs on the X chromosome.
Therefore only boys exhibit the disease. Girls are carriers.
Is the disease inherited?
Yes. Lesch-Nyhan disease is most often inherited
but it can also occur spontaneously as a result of a genetic mutation.
However about 1/3 of the new cases are the result of a spontaneous mutations.
If the mutation occurs in the female, she becomes are carrier.If
it occurs in the male he acquires the disease. When the mother is a carrier
of the disease, there is a 50/50 chance that her male child will have
the disease and a 50/50 chance that her female child will be a carrier.
The disease does not usually stay in families much longer than one or
two or perhaps three generations.
Why does the genetic defect
cause self-injury?
No one knows the answer to this question. Discovering
why this happens will not only be important for understanding Lesch-Nyhan
disease but will also be a major breakthrough in understanding brain-behavior
relationships.
How is the disease diagnosed?
The disease is usually first suspected because of
the orange crystals in the diapers, poor motor control and the behavioral
symptoms of self-injury. The definitive diagnosis is made by assaying
levels of the HPRT enzyme in red blood cells or cultured fibroblasts.
Is it possible to diagnose the
disease prior to birth?
Yes. It is possible to identify the disease prior
to birth by culturing amniotic fluid fibroblasts and assaying for the
enzyme.
What is the life expectancy?
The average life expectancy is somewhere in the
early to mid twenties. It must be remembered that this is an average that
has a considerable range. With good medical and psychological care the
patients can live to be much older.
What are the causes of death?
Kidney failure was once the main cause of death.
When the drug allopurinol is properly used to decrease serum uric acid
the kidney damage is significantly slowed . Allopurinol has been in use
for over twenty years and renal failure is no longer the leading cause
of death. There have been no systematic surveys to determine the more
recent causes of death. It is impression that some of the deaths may lack
a specificity of cause. The patients get progressively weaker, breathe
with greater difficulty, eat more poorly and become less and less interested
in people and their surroundings. Losing the will to survive may explain
some of the deaths. Patients who are content with themselves seem do the
best.
What are the cognitive and
intellectual abilities of patients with LND?
The patients seem to be completely normal in many
of the ways cognitive and intellectual abilities are measured. They have
an excellent memory, their emotional life is appropriate, they have good
concentration, they are capable of abstract reasoning, they have good
self-awareness and are highly social. On the other hand, it is clear they
are below expectation in traditional forms of academic ability. Most patients
appear to have a specific learning disability in the areas of math and
reading.
Cognitive and intellectual abilities are difficult to assess because of such things as uncoordinated movement, unintelligible speech, deliberate and misleading mistakes during testing, the difficulty of arranging appropriate schooling, monitoring of progress, feedback, etc. All of this has made intellectual measurement a contentious issue among researchers, teachers and parents.
What are Lesch-Nyhan "Behaviors"?
The disease is best known for its behavioral characteristics.
The "classic" behavior is a unique form of severe self-injurious behavior
(SIB). Children as young as two years of age will bite their fingers,
lips and the inside of their mouths. If not physically restrained the
injury can become severe, resulting in the loss of fingers and lips. As
they get older the self-injury will transform into a wide variety of other
ways of physical harm as patients cleverly devise new and unexpected ways
to "deliberately" hurt themselves. "Deliberate" is in quotations because
it is clear that the patients do not want to hurt themselves. They cry
out in pain and plead to be restrained.
While physical self-injury is the most salient characteristic, there are other behaviors common to patients with LND. Not only do they physically injure themselves but they say and do things that cause themselves considerable psychological harm. Also, They will strike out against others in both physical and psychological ways. And they do deliberate psychological harm to themselves.
The behavior is often directed at others. the patients attempt to hurt others by head snapping, pinching, arm swinging, or spitting. This striking out against others can be psychological and verbal as well. They will curse at a friend, favorite caretaker, or parent. They will deliberately lie in a way that harms their own interests. They may give the wrong answer to test question or say no when asked if they want get fast food or a movie. It seems inexpliciable that they want to hurt themselves, hurt and abuse favorite friends, and say no when they really want to say yes.
The nature of the Lesch-Nyhan behavior may best be characterized as "doing the opposite" of what is intend. A disinhibition theory rather than an SIB theory might better fit the data
The last thing they want to do is hurt themselves, hurt and abuse favorite friends and say "no" when asked if they want to go on an outing to McDonald's.
Is there any medication that
can cure Lesch-Nyhan Disease?
No. No drug is available to cure the disease. However
some medications are necessary for physical health and some are useful
in alleviating the muscular and behavioral symptoms. The drug allopurinol
must be given to prevent kidney damage by uric acid. But, the successful
treatment of uric acid has no effect on the motor or behavioral problems.
Valium, is one of the common medications given to help improve the quality
of the day. Valium helps relax the muscles and can keep the patient calm
and psychologically more at ease. Some parents and doctors feel that haloperidol,
a neuroleptic, is useful in alleviating the behavioral symptoms. There
are some clinical reports that anti-convulsant medications (Gabapentine)
may be useful. Some parents have reported benefit from Risperidol. Bed
time medications such as Benadryl and chloral hydrate can be used to give
patients and caretakers a better night sleep.