Lesch Nyhan Syndrome LNS

							Lesch-Nyhan Syndrome (LNS)


By:
Amir Sadafi and
Bela Mohapatra
What is LNS?
   LNS is a genetic disorder first discovered in
    1964 by Michael Lesch and William Nyhan.
   It is a recessive disease that is linked to the X
    chromosome
   It is caused by a deficiency of the enzyme
    hypoxanthine-guanine
    phosphoribosyltransferase (HPRT)
Symptoms of LNS
All of the following are a result of an overproduction of Uric Acid
   Urate crystal formations,               Athetosis (uncontrolled
    which look like orange                   spastic muscle movements
    sand, are deposited in                   of the arms and legs)
    diapers of the babies                   Involuntary writhing
   Kidney stones                            movements
   Blood in the urine                      Chorea (purposeless
   Dysphagia (difficulty                    repetitive movements)
    swallowing)                             Moderate mental
   Swelling of the joints                   retardation
   Vomiting                                Irritability
    Clinical Elements
   Overproduction of Uric Acid
    - associated with hyperuricernia
    - can produce Nephrolithiasis (kidney stones) with renal failure
    and solid subcutaneous deposits (tophi)
   Neurological disability
    - includes dystonia (abnormal firmness of tissue or muscle),
    choreoathetosis (abnormal movement of body), and occasional
    ballismus (jerky movement of arms or legs)
    - other signs include spasticity and hyperreflexia
   Behavioral Elements
    - cognative disfunction and aggressive and impulsive behaviors
    -severe self injurious behavior is common
HPRT’s role in the body
   Hypoxanthine-guanine phosphoribosyltransferase is an
    enzyme that plays a key role in the recycling of the
    purine bases, hypoxanthine, and guanine into purine
    nucleotide pools
   Without HPRT the purine bases are broken down and
    excreted as uric acid
   Since these purine bases cannot be reused, the
    production of purine bases is increased
   Both of these together cause a significant overproduction
    of uric acid
Hyperuricemia
   Hyperuricemia is an unusually high concentration of uric
    acid in the blood
   Since the blood usually already has a high concentration of
    uric acid, the increased uric acid solidifies and deposits in
    the tissues forming tophi
   The deposits in the joints cause inflammation and gouty
    arthritis
   The kidneys excrete the extra uric acid, which increases risk
    of urate stones forming
   The stones may pass as a sandy sludge or may obstruct
    urine flow
   This increases the risk for hematuria and urinary tract
    infections
Statistics
   Frequency:
    -Reported prevalence is 1 per 380,000
   Mortality:
    -Few patients live beyond 40 years.
    -The drug allopurinol is used to control
    hyperuricernia. Most patients experience progressive
    dysphagia (difficulty swallowing) and die after
    pneumonia .
    -Also common is sudden unexpected death, even to
    patients in stable medical condition.
   Race:
    -LNS effects most races with equal frequency.
LNS and Cerebral Palsy

   “Cerebral palsy is a group of movement
    disorders that result from damage to the
    brain, either before, during or shortly
    after birth.”
   Thus, LNS is often the cause of the
    damage to the brain that triggers cerebral
    palsy
Treatment and Prognosis
   Treatment:
    -LNS itself cannot be treated
    -Only the symptoms of LNS can be treated.
    -The drug allopurinol may be used to control excessive amounts of
    uric acid.
    -Kidney stones can be treated with lithotripsy
    -There are unfortunately no treatments for the behavioral and
    neurological effects of LNS
   Prognosis:
    -The prognosis for LNS is poor because there are no treatments for
    the neurological effects of the syndrome.
    -The build-up of excessive uric acid in the body causes painful
    episodes of self-mutilation and may result in severe retardation
    and death.
X-Linked Recessive Inheritance
Bibliography
   http://www.guidinghands.org/faqs/cerebr
    alpalsy.htm
   http://www.emedicine.com/neuro/topic63
    0.htm
   http://www.ninds.nih.gov/disorders/lesch
    _nyhan/lesch_nyhan.htm
   http://depts.washington.edu/genetics/cou
    rses/genet371b-
    aut00/public_html/problems/371B_practic
    e_key_02.html