Lesch-Nyhan Syndrome

Deepu Nair
What is the Lesch-Nyhan
Syndrome?

“Lesch-Nyhan
syndrome (LNS) is a
rare (only 1 in
380,000 people have
it), inherited disorder
caused by a
http://www.specialchild.com/archives/poster-child061.jpg
deficiency of the
enzyme
hypoxanthine-
guanine
phosphoribosyltransf
erase (HPRT).” –
What is the Lesch-Nyhan
syndrome
It is often
characterized by the
overproduction of
Uric Acid in the body.
http://billyteoh.files.wordpress.com/2008/07/uric-
acid.png

Uric acid is created as

the final product of
purine metabolism.
Uric acid may be
found in human
blood or urine.
http://www.advancedhealthireland.com/images/Uric_Acid_Resized.jp
g
What is the Lesch-Nyhan
syndrome


Neurological disability
and behavioral
problems are also
characteristic of the
http://www.integrarehab.org/upload/images/Integra/images/may_14t
Lesch-Nyhan
h/5095299-965x724resized.jpg
syndrome.
What are the symptoms?
Overproduction of uric
acid may cause
gouty arthritis,
kidney stones and
http://www.casestudy
md.com/images/Ly-
http://www.pharmainfo.
net/files/images/stories
bladder stones. It
gout_figure1.jpg /article_images/Kidney
_stone_photographs.jp
also results in sandy
g
diapers (uric acid
crystals).

Basillimus (violent
flinging movement
of limbs)
http://www.ojrd.com/content/figures/1750-1172-2-48-2-l.jpg
What are the symptoms
May have difficulty
walking, may need
assistance. A good
number of Lesch-
http://api.ning.com/files/up8slmTl9Uad9B
Nyhan afflicted are
8cfnrktgNvZhz8Mxye1jJakJJKciqPYrxppZt
8- wheel chair bound.
Nhfyb4kGzlJeKh0H8lV3m2*8XBPbzthZcK
3v6R2k4QB/CallumSnowboarding1.jpg 

Moderate mental
retardation

http://api.ning.com/files/up8slmTl9UYtT1KpVSDOvgtMIyTE4A2PIP9qd
cXnI-
KzLwzHV6KNVkYtKvIGXIMEoDcgZwg2hzdKuTllzh16810zdtkt9WwA/Cl
oseUpRestraints1.jpg
What are the symptoms
Aggressive and
impulsive behaviors
(including self-
injurious behavior,
behavior that may
http://api.ning.com/files/up8slmTl9UbJaz7zl1UUni4yTZdy7H-
injure others,
mW9uoEZJG03XjsgP3CitfMtji6agLzKPeqsGu2EPwL7srNggdteRfr-
q5Mjv4a*Kp/AdamHeslopChangingMat1.jpg profane language,
and sexually
charged language)
Spasticity, dystonia
(involuntary spasms
http://www.aurorahealthcare.org/healthgate/images/si55551399.jpg
and muscle
contraction)
 What are the symptoms
Speech impairment
Blood in urine, painful
urination
Pain and swelling in
http://www.aboutjointhealth.com/common/imagelib/index.htm/252_3
00_198_crop_a2635.jpg
the joints



Difficulty swallowing
and eating
http://www.healthpointplaza.com/images/photos/rehab/swallowing5
w21_xpjr.jpg
What are the symptoms
Vomiting
Impaired kidney
function

http://webrheum.bham.ac.uk/professional/general/images/6
411_5.gif



Irritability


http://api.ning.com/files/aeWRTgZyRHpYNL4EMAaurCsKhUmO51ac5
wRMZtPnYEHglMokoB3jtZyedDj0NprqRPedfhH0cFuKHs4fxrnPF171Zjh
*W9Xe/Pictures994.jpg
Interesting facts
Unlike a lot of
genetically inherited
disorders, the Lesch-
Nyhan syndrome
occurs in all
ethnicities with
about the same
frequency.
Historical background
The Lesch-Nyhan
syndrome was
discovered by
Michael Lesch and
William “Bill” Nyhan
http://graphics8.nytimes.com/images/2008/03/27/us/lesch190.jpg
when they met two
brothers afflicted by
hyperuricemia.
They published their
findings in 1964
about the brothers
http://upload.wikimedia.org/wikipedia/en/thumb/7/7e/Nyhan.jpg/150 aged 4 and 8.
px-Nyhan.jpg
Historical background


In 1967 (three years
http://www.famousmormons.net/seegmiller.gif
after discovery), the
cause of the Lesch-
Nyhan syndrome
was identified by
Edwin Seegmiller
and William Kelley.
http://www.jci.org/articles/view/26871/files/JCI0526871.f6/medium
Chromosome involved
The Lesch-Nyhan
syndrome is found
on the X-
chromosome.

Thus it is found in the
larger of the two
chromosomes on the
23rd pair of
chromosomes.
http://rettsyndrome.files.wordpress.com/2009/04/x-
chromosome1.jpg
Gene involved
Mutations in the
HPRT1
(hypoxanthine
phosphoribosyltransf
erase 1) gene
causes the Lesch-
Nyhan syndrome.
More than 200
mutations in the X-
chromosome can
http://egp.gs.washington.edu/data/hprt1/hprt1.prettybase.png
cause the Lesch-
Nyhan syndrome.
Locus of Gene
The cytogenic location
of the HPRT1 gene is
Xq26.1 (long arm of
the X-chromosome
at position 26.1).
It is located on base
pairs 133, 421, 922
to 133, 462,361 on
the X-chromosome.
How do people inherit the Lesch-
Nyhan syndrome
The Lesch-Nyhan
Syndrome is
inherited genetically
by an X chromosome
linked recessive
pattern.
Thus, the Lesch-
Nyhan syndrome is
more common in
http://www.web-
males than in
books.com/eLibrary/Medicine/Appendix/XlinkRecessiveX.jpg
females
Diagnosis
The Lesch-Nyhan
syndrome can easily
be diagnosed
through many ways.
It can be diagnosed
http://www.vet.upenn.edu/Portals/0/images/research/blood_testing.j
pg
either genetically,
through observing
sand-like crystals in
the child’s diapers,
or through observing
high levels of uric
acid in the blood.
http://www.wdr.de/themen/politik/nrw03/dna_beweis/_img/dna_bewe
is_ap_400q.jpg
Prognosis
The prognosis for
people affected by
the Lesch-Nyhan
syndrome isn’t very
positive.

Most people affected
by the Lesch-Nyhan
syndrome die within
the first one or two
decades due to renal
failure.
 Cure?
Currently the Lesch-
Nyhan syndrome
doesn’t have a cure
for adults.
The Lesch-Nyhan
syndrome can be
http://www.co.pierce.wa.us/xml/servi
cured in vitro
ces/home/environ/waste/syringe.jpg though.
Though the syndrome
itself can’t be cured,
there is a treatment
http://www.free-graphics.com/clipart/Health/tablets.jpg

for the Lesch-Nyhan

syndrome.
Treatment
Since there is no cure
to the Lesch-Nyhan
syndrome, the
treatment of the
condition is purely
symptomatic.
Allopurinol may be
used to control
gouty arthritis .
http://www.vetpetmed.com/images/ALLOPURINOL.jpg Allopurinol also
lowers the level of
uric acid in the body.
Treatment
In order to treat the
kidney or bladder
stones, lithotripsy (a
non-invasive form of
treatment that uses
http://www.rxzone.us/images/products/big/561225.jpg
high intensity
acoustic pulses) may
be used.
Carbidopa, diazepam,
and phenobarbital,
haloperidol may be
used to alleviate
immediate
http://www.urologytour.com/images/Lithotripsy.jpg

behavioral issues.
Treatment
The spasticity can be
treated by baclofens
and
benzodiazepines.
In order to avoid self-
http://www.drugs.ie/fs/img/drugs/bensodiazepines.jpg
mutilation restraints
are used.
Unfortunately there’s
no existing solution
for the involuntary
motor movements of
http://api.ning.com/files/xkVCMRT4uG-O3Gi5gw6KS3H-nroPHwZmT- Lesch-Nyhan
patients.
xChrLSUKHCUHRvO4op18e3MED8VxS3IB8EBpRKoVTvE79D7LEuObr
SSe2YNjxr/bedstraps.JPG
Potential cures being explored
In studies conducted
with both “deep
brain stimulation
treatment “and “S-
adenosyl methionine
treatment”, a major
improvement in the
neurobehavioral
condition of patients
was observed.
http://pcnews.ro/wp-content/uploads/2008/02/_dbs-depression-
side300.jpg
Potential cures being explored
Therapy through
creating Induced
pluripotent Stem
cells from the
somatic cells of the
patient and then
using them for
research.
Gene targeting the
http://www.copewithcytokines.de/genetarget.gif

concerned gene and

rectifying the
disorder.
Resources Used
 Augoustides-Savvopoulou et al, P. (2009, July). Partial
Hypoxanthine-Guanine Phosphoribosyltransferase
Deficiency as the unsuspected cause of renal disease
spanning three generations: a cuationary tale.
Retrieved July 23, 2009, from Journal of the American
Academy of Pediatrics Web site:
http://pediatrics.aappublications.org/cgi/reprint/109/1/e17
(Augoustides-Savvopoulou, 2009)
 Callahan, G N. (2005, February). First Self. Emerging
Infectious Diseases Journal, 11, Retrieved July 13,
2005, from
http://www.cdc.gov/ncidod/eid/vol11no02/333.htm
(Callahan, 2005)
 Glick, Norris (2006, August). Dramatic reduction in self-
injury in lesch-nyhan disease following S-
adenosylmethionine administration. Retrieved July 23,
2009, from Springer Link Home Web site:
http://www.springerlink.com/content/6697j71366636878/fulltext.pdf
 Jinnah, H A (2009. April). Lesch-Nyhan disease: from
mechanism to model and back again. Retrieved July
23, 2009, from Disease models and mechanisms Web
site:
http://dmm.biologists.org/content/2/3-4/116.full?maxtoshow=&HITS=&hits=&RESULTFORMAT=&fulltext=lesch-nyhan&andorexa
 NIH, (2009, July). HPRT1. Retrieved July 23, 2009, from
National Institutes of Health Web site:
http://ghr.nlm.nih.gov/gene=hprt1
 NIH, (2009, July). Lesch-Nyhan Syndrome. Retrieved July
23, 2009, from National Institutes of Health Web site:
http://ghr.nlm.nih.gov/condition=leschnyhansyndrome
 NIH, (2009). Lesch-Nyhan Syndrome. Retrieved July 23,
2009, from National Institutes of Health Web site:
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..
ShowSection&rid=gnd.section.298
 NIH, (2007, February). Lesch-Nyhan Syndrome Information
page. Retrieved July 23, 2009, from National Institutes
of Health Web site:
http://www.ninds.nih.gov/disorders/lesch_nyhan/lesch_nyhan.h
 Nyhan, W L. (2000, June). Dopamine Function in Lesch-
Nyhan disease. Retrieved July 23, 2009, from PubMed
Central Homepage Web site:
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=16378
 Nyhan, W L (1997). The recognition of Lesch – Nyhan
syndrome as an inborn error of purine metabolism.
Retrieved July 23, 2009, from Springer Link Home Web
site:
http://www.springerlink.com/content/h08t61073t623565/fullte
 Richard, P (2007, August). An error in the code. Retrieved
July 23, 2009, from The New Yorker Web site:
http://www.newyorker.com/reporting/2007/08/13/070813fa_fac
 Seegmiller, JE (1967). Enzyme defect associated with a
sex-linked human neurological disorder and excessive
purine synthesis. Retrieved July 23, 2009, from Science
Magazine Web site:
http://www.sciencemag.org/cgi/reprint/155/3770/1682
 Ye et al., L (2009, April). Induced pluripotent stem cells
offer new approach to therapy in thalassemia and
sickle cell anemia and option in prenatal diagnosis in
genetic diseases. Retrieved July 23, 2009, from
Proceedings of the National Academy of Sciences Web
site:
http://www.pnas.org/content/106/24/9826.full?maxtoshow=&H