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Lesch-Nyhan syndrome (LNS) is an inherited disorder transmitted by

sex linked traits. It is a rare x-linked disorder of purine metabolism due to
deficiency of hypoxanthine phosphoribosyltransferase (HGPRT). At first year
of their life, individuals are normal but then it will later develop irritability
and neurological symptoms and a later on it will be more severe because it
can make the person aggressive as he will bang his head and biting lips,
fingers and hands etc. Lack of HGPRT can affect the body severely because
this can cause the body to poorly utilize vitamin B12 and it can cause boys to
develop a rare disorder called megaloblastic anemia.
Epidemiology
LNS is a very rare disease because it is estimated that out of 380,000
live births only one can have this. LNS disease is carried by mother that is
pass to her son. Males get LNS when there is a gene mutation HGPRT gene in
X-chromosomes and since normal X-chromosomes protect females, they
dont get this disease. Females are known to be silent carriers because they
carry this disease. When mothers who are silent carriers have a son there is
a possibility that their son will suffer from LNS and it is also possible that
their son is healthy. But when the mothers who are silent carriers have a
daughter, their daughter will also be a silent carrier. Since boy inherits Xchromosomes from mother, mothers are the ones who can only transmit
disease and father cant transmit disease to their sons.
Whenever there is a pregnancy, there is 50% chance that their
son/daughter will be normal but then there is 25% chance that their son will
be affected by LNS disease and also 25% that their daughter will be a silent
carrier of LNS. Not all boys who suffer from LNS does not get their diseases
from mother, they can get LNS disease also if there is a mutation in the
HGPRT gene that is occurred very early during their development. From first
year of life, LNS is a rare disease that can affect young children in a very
young age. It is reported that almost all races can have this LNS disease
mostly ethnic groups.
Symptoms
Lesch-Nyhan syndrome is characterized by overproduction of uric acid,
neurologic dysfunction and cognitive and behavioral disturbances.
Development of uric acid crystals and stones can be the effect of
overproduction of uric acid. These crystals and stones may develop or form
to three main parts of the body. First area is where the joints between bones
especially in our fingers and toes. These crystals can cause the irritation that
can lead the fingers and toes to be swollen painful and red and this is called
Gout. Second area where these can form is under the skin in cool parts of
body. Tophi can be seen through your skin which is a deposit of monosodium
urate crystals to people with high level of uric acid. Lastly, the most
dangerous place for the stone to form is in our kidney. This will cause a

kidney failure because these large stones can possibly block the way of urine
and these causes pain to belly, back and upper leg.
Irritability is most commonly seen in first signs of nervous system
impairment. It can also abnormally decreased muscle tone which can be
called hypotonia and developmental delay so there is a failure in reaching
normal actions like sitting, crawling and walking.
People who suffer from Lesch-Nyhan disease always suffer from
Cognitive and behavioural disturbances because they often hit others,
spitting on others and using foul language towards them. They always do
these aggressive things but unluckily they cant control it. Children with LNS
can also have developed problem behaviours because they attempt to hit or
injure themselves. They also bite their lips and other parts of their body.
Biochemical Basis Explaining Selected Symptoms
Since the HGPRT is absent in these disease, purine bases cannot be
salvaged so they are degraded and excreted as uric acid. The failure of
purine recycling and addition to the increased of purine can lead to
overproduction of uric acid which leads to hyperuricemia. Neurochemical and
neuroimaging studies have demonstrated that the abnormalities of
dopamine neuron function in the basal ganglia can be the reason for
abnormalities in neurological and behavioural sections.
Molecular Basis of Diagnosis
There are three simple steps for the diagnosis of LNS disease. First is
clinical assessment, it will involve a thorough medical evaluation like the
summary o how the child develops and the childs in physical examination.
LNS disease can be first suspected if the child have self-inflicted injury like
biting of fingers and lips. Second step includes tests like getting blood and
urine samples for uric acid. Since the high levels of uric acid are a symptom
of LNS disease, there is a suspection if the test resulted to a high level of uric
acid. Lastly, there should be a genetic coundeling like asking information
from family if there are implications and genetic disorders. The childs
mother should also be checked since LNS disease cant be seen in females.
Therapeutic Remedies
To control the overproduction of uric acid, uric acid should be
maintained in normal levels. Control of uric acid requires two main
components which are Allopurinol which is effective in limiting hyperuricemia
and its consequences. The dose is titrated to bring serum uric acid to normal
levels. Another main component is generous hydration all the time since
there is an increased of fluid loss. Consultation can also be done to inform
the family the risk of additional children with this disorder. If there is a joint
complication, surgical specialist may be required to help. Nephrolithiasis may
require surgical intervention for extraction of stones or relief from urogenital

obstruction. It is also said that self-injury and dystonia can be controlled by

having a deep brain stimulation surgery.
References
[1] PubMed.Gov. From: http://www.ncbi.nlm.nih.gov/pubmed/20301328
[2]Genetics Home Reference. Lesch-Nyhan syndrome. From: http://ghr.nlm.nih.gov/condition/leschnyhan-syndrome
[3] Lesch-Nyan Syndrome. From: http://omim.org/entry/300322
[4] Lavoro svolto da Elena Asteggiano. Lesch Nyhan Syndrome. From:
http://flipper.diff.org/app/items/3359
[5]http://www.diseasesdatabase.com/umlsdef.asp?glngUserChoice=7415