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'''For patient information click [[Lesch-Nyhan's syndrome (patient information)|here]]'''
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{{Infobox_Disease |
{{Infobox_Disease |
   Name        = Lesch-Nyhan syndrome |
   Name        = Lesch-Nyhan syndrome |
   Image      = Philip_Baker.jpg |
   Image      = Philip_Baker.jpg|50px|
   Caption    = Philip Baker, an adult with Lesch-Nyhan Syndrome. Visible in this picture are the restraints on Philip's chair that he must use to control his involuntary movement. |
   Caption    = Philip Baker, an adult with Lesch-Nyhan Syndrome. Visible in this picture are the restraints on Philip's chair that he must use to control his involuntary movement. |
  Width      = 200px
   ICD10      = {{ICD10|E|79|1|e|70}} |
   ICD10      = {{ICD10|E|79|1|e|70}} |
   ICD9        = {{ICD9|277.2}}|
   ICD9        = {{ICD9|277.2}}|
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   eMedicineTopic = |
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{{SI}}
{{Lesch-Nyhan syndrome}}
{{CMG}}
'''For patient information click [[Lesch-Nyhan syndrome (patient information)|here]]'''


==Overview==
{{CMG}}; {{AE}} {{AN}}
'''Lesch-Nyhan's syndrome''' ('''LNS'''), also known as '''Nyhan’s syndrome''', is a rare, [[inherited disorder]] caused by a deficiency of the [[enzyme]] [[hypoxanthine-guanine phosphoribosyltransferase]] (HGPRT). LNS is an [[X-linked recessive]] disease: the [[gene]] is carried by the mother and passed on to her son.  LNS is present at [[childbirth|birth]] in baby boys. Patients have severe mental and physical problems throughout life. The lack of HPRT causes a build-up of [[uric acid]] in all body fluids, and leads to problems such as severe [[gout]], poor muscle control, and moderate [[mental retardation]], which appear in the first year of life.  A striking feature of LNS is self-mutilating behaviors, characterized by lip and finger biting, that begin in the second year of life. 


Abnormally high [[uric acid]] levels can cause sodium urate crystals to form in the [[joint]]s, [[kidney]]s, [[central nervous system]] and other tissues of the body, leading to gout-like swelling in the joints and severe kidney problems. Neurological symptoms include facial grimacing, involuntary writhing, and repetitive movements of the arms and legs similar to those seen in [[Huntington's disease]]. The direct cause of the neurological abnormalities remains unknown. Because a lack of HGPRT causes the body to poorly utilize [[vitamin B12]], some boys may develop a rare disorder called [[megaloblastic anemia]].<ref name = "NINDSInfo" />
{{SK}} Hypoxanthine-guanine phosphoribosyltranferase deficiency; HGPRT-1 deficiency; HGPRT deficiency; Nyhan's syndrome; LNS


The symptoms caused by the buildup of uric acid ([[arthritis]] and [[renal]] symptoms) respond well to treatment with drugs such as [[allopurinol]] that reduce the levels of uric acid in the blood. The mental deficits and self-mutilating behavior do not respond to treatment. There is no cure, but many patients live to adulthood.  LNS is rare, affecting about one in 380,000 live births.<ref name="GHR"/> It was first described in 1964 by [[Michael Lesch|Dr. Michael Lesch]] and [[William Nyhan|Dr. William Nyhan]].<ref>Ole Daniel Enersen. [http://www.whonamedit.com/synd.cfm/2175.html Lesch-Nyhan syndrome or disease.] [[Who Named It]].  Retrieved on 2007-05-27. </ref>
==[[Lesch-Nyhan syndrome overview|Overview]]==


==Signs and symptoms==
==[[Lesch-Nyhan syndrome historical perspective|Historical Perspective]]==
LNS is characterized by three major hallmarks: [[neurology|neurologic]] dysfunction, [[Cognition|cognitive]] and [[Human behavior|behavioral]] disturbances, as well as [[uric acid]] overproduction ([[hyperuricemia]]). Damage to the [[Basal Ganglia|basal ganglia]] causes victims to adopt a characteristic fencing stance due to the nature of the lesion. Some may also be afflicted with [[anemia]] (macrocytic). Virtually all patients are male, and male victims suffer delayed growth and [[puberty]], and most develop shrunken testicles or [[testicular atrophy]].  Female carriers are at an increased risk for [[gout|gouty arthritis]], but are usually otherwise unaffected. 


===Overproduction of uric acid===
==[[Lesch-Nyhan syndrome pathophysiology|Pathophysiology]]==
One of the first symptoms of the disease is the presence of sand-like crystals of [[uric acid]] in the diapers of the affected infant. Overproduction of uric acid may lead to the development of uric acid crystals or stones in the [[kidneys]], [[ureters]], or [[Urinary bladder|bladder]]. Such crystals deposited in joints later in the disease may produce [[gout]]-like [[arthritis]], with swelling and tenderness.


[[Image:UricAcid.png|thumb|220px|left|uric acid molecule]]
==[[Lesch-Nyhan syndrome differential diagnosis|Differentiating Lesch-Nyhan syndrome from other Diseases]]==
The overproduction of uric acid is present at birth, but may not be recognized by routine clinical laboratory testing methods. The serum uric acid concentration is often normal, as the excess purines are promptly eliminated in the urine. The crystals usually appear as an orange grainy material, or they may coalesce to form either multiple tiny stones, or distinct large stones that are difficult to pass. The stones, or calculi, usually cause [[hematuria]] (blood in the urine) and increase the risk of [[urinary tract infection]]. Some victims suffer kidney damage due to such [[kidney stone]]s. Stones may be the presenting feature of the disease, but can go undetected for months or even years.


===Nervous system impairment===
==[[Lesch-Nyhan syndrome epidemiology and demographics|Epidemiology and Demographics]]==
The periods before and surrounding birth are typically normal in individuals with LNS.  The most common presenting features are abnormally decreased [[muscle]] tone ([[hypotonia]]) and developmental delay, which are evident by three to six months of age. Affected individuals are late in sitting up, while most never crawl or [[walking|walk]]. Lack of [[Speech communication|speech]] is also a very common trait associated with LNS.


Irritability is most often noticed along with the first signs of nervous system impairment.  Within the first few years of life, [[extrapyramidal]] involvement causes abnormal involuntary muscle contractions such as loss of motor control ([[dystonia]]), writhing motions ([[choreoathetosis]]), and arching of the spine ([[opisthotonus]]). Signs of [[pyramidal system]] involvement, including spasticity, overactive reflexes ([[hyperreflexia]]) and extensor [[plantar reflex]]es, also occur. The resemblance to athetoid [[cerebral palsy]] is apparent in the neurologic aspects of LNS. As a result, most individuals are initially diagnosed as having cerebral palsy. The motor disability is so extensive that most individuals never walk, and are confined to a wheelchair for life.
==[[Lesch-Nyhan syndrome screening|Screening]]==


===Self-injuring behavior===
==[[Lesch-Nyhan syndrome natural history|Natural History, Complications and Prognosis]]==
Persons affected are cognitively impaired and have behavioral disturbances that emerge between two and three years of age. The uncontrollable self-injury associated with LNS also usually begins at three years of age. The self-injury begins with biting of the lips and tongue and as the disease progresses, affected individuals frequently develop finger biting and head banging. The self-injury can increase during times of stress.  Self-mutilation is a distinguishing characteristic of the disease and is apparent in 85% of affected males.
 
The majority of individuals are cognitively impaired, which is not easy to determine because of the behavioral disturbances and motor deficits associated with the syndrome.  In many ways, the behaviors may be seen as a psychological extension of the compulsion to cause self-injury: rejecting desired treats or travel, repaying kindness with coldness or rage, failing to answer test questions correctly despite study and a desire to succeed, provoking anger from caregivers when affection is desired, and so on.
 
Compulsive behaviors also occur, including aggressiveness, [[vomiting]], spitting, and involuntary swearing, or [[coprolalia]]. The development of this type of behavior is sometimes seen within the first year, or in early childhood, but others may not develop it until later in life.
 
=== LNS in females ===
While carrier females are generally [[asymptomatic]], they do experience an increase in uric acid excretion, and some may develop symptoms of hyperuricemia, and suffer from gout in their later years. Testing in this context has no clinical consequence, but it may reveal the possibility of transmitting the trait to male children. Women may also require testing if a male child develops LNS. In this instance, a negative test means the son's disease is the result of a new mutation, and the risk in siblings is not increased.
 
Females who carry one copy of the defective gene are carriers with a 50% chance of passing the disease on to their sons. In order for a female to be affected, she would need to have two copies of the mutated gene, one of which would be inherited from her father. Males affected with LNS do not usually have children due to the debilitating effects of the disease. It is possible for a female to inherit an X chromosome from her unaffected father, who carries a new mutation of the HPRT gene. Under these circumstances, a girl could be born with LNS, and though there are a few reports of this happening, it is very rare. The overwhelming majority of patients with LNS are male.


==Diagnosis==
==Diagnosis==
When an affected individual has fully developed the three clinical elements of uric acid overproduction, neurologic dysfunction, and cognitive and behavioral disturbances, diagnosis of LNS is easily made. Difficulties of diagnosis are abundant in the early stages when the three features are not yet obvious. Suspicion often comes about when the developmental delay of the individual is associated with hyperuricemia. Otherwise, the diagnosis should be alleged when developmental delay is associated with kidney stones ([[nephrolithiasis]]) or blood in the urine ([[hematuria]]), caused by uric acid stones. For the most part, Lesch-Nyhan syndrome is first suspected when self-inflicted injury behavior develops. However, self-injurious behaviors occur in other conditions, including nonspecific [[mental retardation]], [[autism]], [[Rett syndrome]], [[Cornelia de Lange syndrome]], [[Tourette syndrome]], [[familial dysautonomia]], [[choreoacanthocytosis]], [[sensory neuropathy]] including hereditary sensory neuropathy type 1, and several psychiatric conditions. Of these, only individuals with Lesch-Nyhan syndrome, de Lange syndrome, and familial dysautonomia recurrently display loss of tissue as a consequence. Biting the fingers and lips is a definitive feature of Lesch-Nyhan syndrome; in other syndromes associated with self-injury, the behaviors usually consist of head banging and nonspecific self-mutilation, but not biting of the cheeks, lips and fingers. Lesch-Nyhan syndrome ought to be clearly considered only when self-injurious behavior takes place in conjunction with hyperuricemia and neurological dysfunction.
===Diagnostic approach===
The urate to [[creatinine]] (breakdown product of creatine phosphate in muscle) concentration ratio in urine is elevated. This is a good indicator of acid overproduction. For children under ten years of age with Lesch-Nyhan syndrome, a urate to creatinine ratio above two is typically found. Twenty-four-hour urate excretion of more than 20 mg/kg is also typical but is not [[diagnosis|diagnostic]]. Hyperuricemia (serum uric acid concentration of >8 mg/dL) is often present but not reliable enough for diagnosis. Activity of the HPRT enzyme in [[Cell (biology)|cells]] from any type of [[Biological tissue|tissue]] (e.g., [[blood]], cultured [[fibroblast]]s, or [[lymphoblast]]s) that is less than 1.5% of normal enzyme activity confirms the diagnosis of Lesch-Nyhan syndrome.
===Testing===
The use of [[biochemistry|biochemical]] testing for the detection of carriers is technically demanding and not often used. Biochemical analyses that have been performed on hair bulbs from at risk women have had a small number of both [[Type I and type II errors|false positive]] and false negative outcomes. If only a suspected carrier female is available for HPRT1 mutation testing, it is appropriate to grow her [[lymphocytes]] in 6-thioguanine (a [[purine|purine analogue]]), which allows only HPRT-deficient cells to survive. A mutant frequency of 0.5-5.0 x 10-2 is found in carrier females, while a non-carrier female has a frequency of 1-20 x 10-6. This frequency is usually diagnostic by itself.
Molecular genetic testing is the most effective method of testing, as HPRT1 is the only gene known to be associated with LNS. Individuals who display the full Lesch-Nyhan [[phenotype]] all have mutations in the HPRT1 gene. Sequence analysis of [[mRNA]] is available clinically and can be utilized in order to detect HPRT1 mutations in males affected with Lesch-Nyhan syndrome. Techniques such as RT-PCR, multiplex genomic PCR, and sequence analysis (cDNA and genomic DNA), used for the diagnosis of genetic diseases, are performed on a research basis. If RT-PCR tests result in cDNA showing the absence of an entire [[exon]] or exons, then multiplex genomic PCR testing is performed. Multiplex genomic PCR testing amplifies the nine exons of the HPRT1 gene as eight PCR products. If the exon in question is deleted, the corresponding band will be missing from the multiplex PCR. However if the exon is present, the exon is sequenced to identify the mutation, therefore causing exclusion of the exon from cDNA. If no cDNA is created by RT-PCR, then multiplex PCR is performed on the notion that most or all of the gene is obliterated.


==Genetics==
[[Lesch-Nyhan syndrome history and symptoms|History and Symptoms]] | [[Lesch-Nyhan syndrome physical examination|Physical Examination]] | [[Lesch-Nyhan syndrome laboratory tests|Laboratory Findings]] | [[Lesch-Nyhan syndrome x ray|X ray]] | [[Lesch-Nyhan syndrome CT|CT]] | [[Lesch-Nyhan syndrome ultrasound|Ultrasound]]
[[Image:XlinkRecessive.jpg|thumb|left|220px|LNS is inherited in an [[X-linked recessive]] fashion.]]LNS is due to [[mutation]]s in the ''HPRT1'' [[gene]],<ref>[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.section.298 Lesch-Nyhan syndrome.] NCBI Genes and disease.  Retrieved on [[2007-04-12]]</ref><ref name="GHR">[http://ghr.nlm.nih.gov/condition=leschnyhansyndrome Lesch-Nyhan syndrome.] Genetics Home Reference.  Retrieved on [[2007-05-24]].</ref> so named because it codes for the [[enzyme]] [[hypoxanthine-guanine phosphoribosyltransferase]] (HPRT or HGPRT, {{EC number|2.4.2.8}}). This enzyme is involved in the biochemical pathways the body uses to produce [[purine]]s, one of the components of [[DNA]] and [[RNA]]. Defects of this enzyme lead to increased production of [[uric acid]]. Since the ''[[HPRT]]'' gene is located on the [[XY sex-determination system|X chromosome]], LNS is an [[X-linked]] inherited disease.
 
The father of an affected male will not be the carrier of the mutant [[allele]], and will not have the disease. An obligate carrier would be a woman who has an affected son and one other affected relative in the maternal line.
 
If a woman is the first in her family with an affected son, [[Haldane's rule]] predicts a 2/3 chance that she is a carrier and a 1/3 chance that the son has a new [[germline mutation]]. However, in this case Haldane's prediction is incorrect due to an increased risk of mutation arising from the father when compared to the mother.
 
The risk to siblings of an affected individual depends upon the carrier status of the mother herself. A 50% chance is given to any female who is a carrier to transmit the HPRT1 mutation in each [[pregnancy]]. Sons who inherit the mutation will be affected while daughters who inherit the mutation are carriers. Therefore, with each pregnancy, a carrier female has a 25% chance of having a male that is affected, a 25% chance of having a female that is a carrier, and a 50% chance of having a normal male or female.
 
Males with LNS do not reproduce due to the characteristics of the disease. However, if a male with a less severe [[phenotype]] reproduces, all of his daughters are carriers, and none of his sons will be affected.
 
==Pathophysiology==
As in other [[X-linked]] diseases, males are affected because they only have one copy of the X chromosome. In Lesch-Nyhan syndrome, the defective gene is that for [[hypoxanthine-guanine phosphoribosyltransferase]] (HPRT), a participant in the [[purine]] metabolism. Female carriers have a second X chromosome, which contains a "normal" copy of HPRT, preventing the disease from developing, though they may have increased risk of hyperuricemia.
 
Various mutations of HPRT are known. Mutations that only mildly decrease the enzyme's function do not normally cause LNS, but do increase susceptibility to [[gout]] and [[nephrolithiasis]].
 
Formation of DNA (during [[cell division]]) requires [[nucleoside]]s, molecules that are the building blocks for DNA. The purines ([[adenine]] and [[guanine]]) and [[pyrimidine]]s ([[thymidine]] and [[cytosine]]) are bound to deoxyribose and phosphate and incorporated as necessary. Normally, the nucleosides are synthetized ''de novo'' from [[amino acid]]s and other precursors. A small part, however, is generated from the degraded DNA of broken-down cells. This is termed the "salvage pathway".
 
HPRT is the "salvage enzyme" for the purines: it channels adenosine (in its hypoxanthine form) and guanine back into DNA synthesis. Failure of this enzyme has two results:
* Cell breakdown products cannot be reused, and are therefore degraded. This gives rise to increased [[uric acid]], a purine breakdown product.
* The ''de novo'' pathway is stimulated due to an excess of PRPP (5-phospho-D-ribosyl-1-pyrophosphate or simply phosphoribosyl-pyrophosphate).
 
It is unclear whether the neurological abnormalities in LNS are due to uric acid neurotoxicity or to a relative shortage in "new" purines during essential steps. Polymorphisms for enzymes in the ''de novo'' pathway may contribute to the disease, but this would not be the case if uric acid neurotoxicity were the main cause of the symptoms. 
 
Moreover, evidence suggests that one or more lesions in [[striatum|striatal]] [[dopamine]]rgic pathways is at least partially responsible for the neurological deficits,  especially the choreoathetoid dyskinesia and self-mutilation.<ref> [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=10852837]</ref><ref> [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=4098945&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum]</ref><ref>{{cite journal |author=Visser J, Smith D, Moy S, Breese G, Friedmann T, Rothstein J, Jinnah H |title=Oxidative stress and dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease |journal=Brain Res Dev Brain Res |volume=133 |issue=2 |pages=127-39 |year=2002 |pmid=11882343}}</ref> Thus, [[6-hydroxydopamine]] toxicity in rodents is a useful animal model for the syndrome.<ref> [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=15708628&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum]</ref>  Another putative animal model, Hyperuricemic syndrome in Dalmatian dogs, presents with the characteristic arthritis and kidney failure,  but not the neurological findings.
 
6-hydroxydopamine damages neurons by oxidative mechanisms.  Similarly,  Hyperuricemic syndrome in Dalmatians responds to treatment with Orgotein,  the veterinary formulation of the antioxidant enzyme [[superoxide dismutase]].<ref> [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=1045695&ordinalpos=109&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum]</ref> [[Uric acid]] is a powerful [[reducing agent]] and likely an important human [[antioxidant]].  E.g., urate is the antioxidant in highest concentration in blood.  However, uric acid can also act as a [[pro-oxidant]],<ref> [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=4680784&ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum]</ref>  particularly at high concentrations like those produced in LNS. Thus, [[free radicals]], [[oxidative stress]], and [[reactive oxygen species]] may play some role in the etiology of Lesch-Nyhan's syndrome.<ref>{{cite journal |author=Bavaresco C, Chiarani F, Matté C, Wajner M, Netto C, de Souza Wyse A |title=Effect of hypoxanthine on Na+,K+-ATPase activity and some parameters of oxidative stress in rat striatum |journal=Brain Res |volume=1041 |issue=2 |pages=198–204 |year=2005 |pmid=15829228}}<br/>* {{cite journal |author=Visser J, Smith D, Moy S, Breese G, Friedmann T, Rothstein J, Jinnah H |title=Oxidative stress and dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease |journal=Brain Res Dev Brain Res |volume=133 |issue=2 |pages=127-39 |year=2002 |pmid=11882343}}<br/>*  {{cite journal |author=Saugstad O, Marklund S |title=High activities of erythrocyte glutathione peroxidase in patients with the Lesch-Nyhan syndrome |journal=Acta Med Scand |volume=224 |issue=3 |pages=281-5 |year=1988 |pmid=3239456}}</ref>  Significantly,  while first proposed for LNS and hyperuricemia in Dalmatian dogs,<ref> [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=78313&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum]</ref>  urate-induced oxidative stress is now thought to also figure in [[metabolic syndrome]], [[atherosclerosis]], and [[stroke]].


==Treatment==
==Treatment==
Treatment for LNS is symptomatic.  Gout can be treated with [[allopurinol]] to control excessive amounts of [[uric acid]].  Kidney stones may be treated with [[lithotripsy]], a technique for breaking up kidney stones using shock waves or laser beams.  There is no standard treatment for the neurological symptoms of LNS.  Some may be relieved with the drugs [[carbidopa]]/[[levodopa]], [[diazepam]], [[phenobarbital]], or [[haloperidol]].<ref name = "NINDSInfo">[http://www.ninds.nih.gov/disorders/lesch_nyhan/lesch_nyhan.htm NIH/NINDS Lesch-Nyhan Information Page.]  NIH/NINDS ([[February 13]] [[2007]]).  Retrieved on [[2007-04-12]]</ref>
It is essential that the overproduction of uric acid be controlled in order to reduce the risk of nephropathy, nephrolithiasis, and gouty arthritis. The drug [[allopurinol]] is utilized to stop the conversion of [[purines|oxypurines]] into uric acid, and prevent the development of subsequent arthritic tophi (produced after having chronic gout), [[kidney stone|renal stones]] (also known as kidney stones), and [[nephropathy]], the resulting kidney disease. Allopurinol is taken orally, at a typical dose of 3–20 mg/kg per day. The dose is then adjusted to bring the uric acid level down into the normal range (<3 mg/dL). Most affected individuals can be treated with allopurinol all through life.
No medication is effective in controlling the [[extrapyramidal]] motor features of the disease. Spasticity, however, can be reduced by the administration of [[baclofen]] or [[benzodiazepines]].
No method of treatment for the neurobehavioral aspects of the disease has been effective. Even children treated from birth with allopurinol develop behavioral and neurologic problems, despite never having had high serum concentrations of uric acid. Self-injurious and other behaviors are best managed by a combination of medical, physical, and behavioral interventions. The self-mutilation is often reduced by using restraints. Sixty percent of individuals have their teeth extracted in order to avoid self-injury, which families have found to be an effective management technique. Because stress increases self-injury, behavioral management through aversive techniques (which would normally reduce self-injury) actually increases self-injury in individuals with LNS. Nearly all affected individuals need restraints to prevent self-injury, and are restrained more than 75% of the time. This is often at their own request, and occasionally involves restraints that would appear to be ineffective, as they do not physically prevent biting. Families report that affected individuals are more at ease when restrained.
An article in the August 13, 2007 issue of The New Yorker magazine, written by Richard Preston, discusses "Deep-brain stimulation," as a possible treatment.  It has been performed on a few patients with Lesch-Nyhan syndrome by Dr. Takaomi Taira in Tokyo and by a group in France led by Dr. Philippe Coubes.  Some patients experienced a decrease in spastic self-injurious symptoms.  The technique was developed for treating people with [[Parkinson's disease]], according to Preston, over 20 years ago.  The treatment involves invasive surgery to place wires that carry a continuous electric current into a specific region of the brain.<ref>[http://www.newyorker.com/reporting/2007/08/13/070813fa_fact_preston</ref>
== Prognosis ==
The prognosis for individuals with LNS is poor.  Death is usually due to renal failure in the first or second decade of life.<ref name = "NINDSInfo"/>
==History==
Michael Lesch was a medical student at [[Johns Hopkins Hospital]], where [[pediatrics|pediatrician]]/pediatric oncologist [[Dr. William Nyhan|Bill Nyhan]] was a faculty member, when the two identified LNS and its associated hyperuricemia in two affected brothers, ages 4 and 8.<ref>Nyhan WL. The recognition of Lesch-Nyhan syndrome as an inborn error of purine metabolism. ''J Inher Metab Dis'' 1997;20:171-8. PMID 9211189.</ref> Lesch and Nyhan published their findings in 1964.<ref>Lesch M, Nyhan WL. A familial disorder of uric acid metabolism and central nervous system function. ''Am J Med'' 1964;36:561-70. PMID 14142409.</ref> Within three years, the metabolic cause was identified by J. Edwin Seegmiller and his colleagues at [[NIH]].<ref>Seegmiller JE, Rosenbloom FM, Kelley WN. Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. ''[[Science (journal)|Science]]'' 1967;155:1682–4. PMID 6020292.</ref>
==Less severe forms==
A less severe related disease is partial HPRT deficiency is known as Kelley-Seegmiller Syndrome (Lesch-Nyhan Syndrome involves total HPRT deficiency). Symptoms generally involve less neurological involvement but the disease still causes gout and kidney stones.<ref>[http://www.japi.org/january2006/CR-49.pdf]</ref><ref>[http://pediatrics.aappublications.org/cgi/content/full/109/1/e17]</ref>


==LNS in popular culture==
[[Lesch-Nyhan syndrome medical therapy|Medical Therapy]] | [[Lesch-Nyhan syndrome primary prevention|Primary Prevention]] | [[Lesch-Nyhan syndrome secondary prevention|Secondary prevention]]
LNS is one of the subjects treated in Richard Preston's fictional account of a biological-weapons attack on the New York subway system, ''The Cobra Event''.
 
Richard Preston, ''An Error in the Code -- A syndrome poses questions about free will'', The New Yorker, August 13, 2007, p. 30, is a report examining developments in medicine’s understanding of LNS, with stories of some patients' experiences.<ref>[http://www.newyorker.com/reporting/2007/08/13/070813fa_fact_preston Abstract]</ref>
 
==References==
{{reflist|2}}


==External links==
==External links==
*[http://www.CLIMB.org.uk CLIMB] (Children Living with Inherited Metabolic Diseases)
*[http://www.lndinfo.org Lesch-Nyhan Syndrome Registry]
*[http://www.rarediseases.org National Organization for Rare Disorders (NORD)]
*[http://www.nichd.nih.gov National Institute of Child Health and Human Development (NICHD)]
*[http://www.nichd.nih.gov National Institute of Child Health and Human Development (NICHD)]
*[http://hometown.aol.com/pbaker71/myhomepage/profile.html Philip Baker's Homepage]
{{Endocrine, nutritional and metabolic pathology}}
* [http://www.clevelandclinic.org/health/health-info/docs/1200/1297.asp?index=6035 Lesch-Nyhan Syndrome.] The Cleveland clinic.  Retrieved on 2007-04-12.
*[http://web.archive.org/web/20050403230609/http://www.chclibrary.org/micromed/00054660.html Lesch-Nyhan Syndrome.] Joseph F. Smith medical library.  Retrieved from the internet archive, April 03 2005 version on 2007-04-12.


{{Endocrine, nutritional and metabolic pathology}}
{{SIB}}


[[Category:Pediatrics]]
[[Category:Pediatrics]]

Latest revision as of 03:45, 28 August 2012

Lesch-Nyhan syndrome
Philip Baker, an adult with Lesch-Nyhan Syndrome. Visible in this picture are the restraints on Philip's chair that he must use to control his involuntary movement.
ICD-10 E79.1
ICD-9 277.2
OMIM 308000 300322
DiseasesDB 7415
MedlinePlus 001655

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Synonyms and keywords: Hypoxanthine-guanine phosphoribosyltranferase deficiency; HGPRT-1 deficiency; HGPRT deficiency; Nyhan's syndrome; LNS

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da:Lesch-Nyhans syndrom de:Lesch-Nyhan-Syndrom it:Sindrome di Lesch-Nyhan


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