U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Lesch-Nyhan syndrome(LNS)

MedGen UID:
9721
Concept ID:
C0023374
Disease or Syndrome
Synonym: LNS
SNOMED CT: Lesch-Nyhan syndrome (10406007); Complete HGPRT deficiency (10406007); Choreoathetosis self-mutilation syndrome (10406007); Total HGPRT deficiency (10406007); HGPRT deficiency (10406007); HPRT - Hypoxanthine-guanine phosphoribosyltransferase deficiency (10406007); Complete hypoxanthine-guanine phosphoribosyltransferase deficiency (10406007); Lesch-Nyhan disease (10406007); Hypoxanthine-guanine phosphoribosyltransferase deficiency (10406007); X-linked hyperuricemia (10406007)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): HPRT1 (Xq26.2-26.3)
 
Monarch Initiative: MONDO:0010298
OMIM®: 300322
Orphanet: ORPHA510

Disease characteristics

Excerpted from the GeneReview: HPRT1 Disorders
HPRT1 disorders, caused by deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt), are typically associated with clinical evidence for overproduction of uric acid (hyperuricemia, nephrolithiasis, and/or gouty arthritis) and varying degrees of neurologic and/or behavioral problems. Historically, three phenotypes were identified in the spectrum of HPRT1 disorders: Lesch-Nyhan disease (LND) at the most severe end with motor dysfunction resembling severe cerebral palsy, intellectual disability, and self-injurious behavior; HPRT1-related neurologic dysfunction (HND) in the intermediate range with similar but fewer severe neurologic findings than LND and no self-injurious behavior; and HPRT1-related hyperuricemia (HRH) at the mild end without overt neurologic deficits. It is now recognized that these neurobehavioral phenotypes cluster along a continuum from severe to mild. [from GeneReviews]
Authors:
Hyder A Jinnah   view full author information

Additional description

From MedlinePlus Genetics
Lesch-Nyhan syndrome is a condition that occurs almost exclusively in males. It is characterized by neurological and behavioral abnormalities and the overproduction of uric acid. Uric acid is a waste product of normal chemical processes and is found in blood and urine. Excess uric acid can be released from the blood and build up under the skin and cause gouty arthritis (arthritis caused by an accumulation of uric acid in the joints). Uric acid accumulation can also cause kidney and bladder stones.

The nervous system and behavioral disturbances experienced by people with Lesch-Nyhan syndrome include abnormal involuntary muscle movements, such as tensing of various muscles (dystonia), jerking movements (chorea), and flailing of the limbs (ballismus). People with Lesch-Nyhan syndrome usually cannot walk, require assistance sitting, and generally use a wheelchair. Self-injury (including biting and head banging) is the most common and distinctive behavioral problem in individuals with Lesch-Nyhan syndrome.  https://medlineplus.gov/genetics/condition/lesch-nyhan-syndrome

Clinical features

From HPO
Nephrocalcinosis
MedGen UID:
10222
Concept ID:
C0027709
Disease or Syndrome
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Testicular atrophy
MedGen UID:
57626
Concept ID:
C0156312
Disease or Syndrome
Wasting (atrophy) of the testicle (the male gonad) manifested by a decrease in size and potentially by a loss of fertility.
Nephrolithiasis
MedGen UID:
98227
Concept ID:
C0392525
Disease or Syndrome
The presence of calculi (stones) in the kidneys.
Hyperuricosuria
MedGen UID:
182691
Concept ID:
C0948643
Finding
An abnormally high level of uric acid in the urine.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Self-injurious behavior
MedGen UID:
88371
Concept ID:
C0085271
Individual Behavior
Self-aggression.
Choreoathetosis
MedGen UID:
39313
Concept ID:
C0085583
Disease or Syndrome
Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements).
Opisthotonus
MedGen UID:
56246
Concept ID:
C0151818
Sign or Symptom
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Abnormality of extrapyramidal motor function
MedGen UID:
115941
Concept ID:
C0234133
Sign or Symptom
A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless).
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Megaloblastic anemia
MedGen UID:
1527
Concept ID:
C0002888
Disease or Syndrome
Anemia characterized by the presence of erythroblasts that are larger than normal (megaloblasts).
Hip dislocation
MedGen UID:
42455
Concept ID:
C0019554
Injury or Poisoning
Displacement of the femur from its normal location in the hip joint.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Podagra
MedGen UID:
450998
Concept ID:
C0221168
Disease or Syndrome
Gout affecting the Metatarsophalangeal joint of big toe.
Poor head control
MedGen UID:
322809
Concept ID:
C1836038
Finding
Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months.
Hyperuricemia
MedGen UID:
149260
Concept ID:
C0740394
Disease or Syndrome
An abnormally high level of uric acid in the blood.

Term Hierarchy

Professional guidelines

PubMed

Krajewski O, Opiełka M, Urbanowicz K, Chojnowski K, Kochany P, Pawłowski K, Tomaszewska J, Peters GJ, Smoleński RT, Bełdzińska MM
Neurosci Biobehav Rev 2024 Oct;165:105847. Epub 2024 Aug 6 doi: 10.1016/j.neubiorev.2024.105847. PMID: 39117131
Sabus A, Feinstein J, Romani P, Goldson E, Blackmer A
Pharmacotherapy 2019 Jun;39(6):645-664. Epub 2019 Mar 27 doi: 10.1002/phar.2238. PMID: 30793794Free PMC Article
Crawhall JC, Henderson JF, Kelley WN
Pediatr Res 1972 May;6(5):504-13. doi: 10.1203/00006450-197205000-00004. PMID: 4558815

Curated

Torres RJ, Puig JG, Ceballos-Picot I
Eur J Hum Genet 2011 Jan;19(1):preceeding 118-20. Epub 2010 Jul 21 doi: 10.1038/ejhg.2010.109. PMID: 20648055Free PMC Article

Recent clinical studies

Etiology

Cagiada M, Bottaro S, Lindemose S, Schenstrøm SM, Stein A, Hartmann-Petersen R, Lindorff-Larsen K
Nat Commun 2023 Jul 13;14(1):4175. doi: 10.1038/s41467-023-39909-0. PMID: 37443362Free PMC Article
Pearson TS, Pons R, Ghaoui R, Sue CM
Mov Disord 2019 May;34(5):625-636. Epub 2019 Mar 26 doi: 10.1002/mds.27655. PMID: 30913345
Fu R, Chen CJ, Jinnah HA
Mol Genet Metab 2014 Aug;112(4):280-5. Epub 2014 May 28 doi: 10.1016/j.ymgme.2014.05.012. PMID: 24930028Free PMC Article
Limeres J, Feijoo JF, Baluja F, Seoane JM, Diniz M, Diz P
Dent Traumatol 2013 Feb;29(1):8-14. Epub 2012 Feb 20 doi: 10.1111/j.1600-9657.2012.01121.x. PMID: 22340154
Pais VM Jr, Lowe G, Lallas CD, Preminger GM, Assimos DG
Urology 2006 May;67(5):1084.e9-11. doi: 10.1016/j.urology.2005.10.057. PMID: 16698380

Diagnosis

Pearson TS, Pons R, Ghaoui R, Sue CM
Mov Disord 2019 May;34(5):625-636. Epub 2019 Mar 26 doi: 10.1002/mds.27655. PMID: 30913345
Fu R, Chen CJ, Jinnah HA
Mol Genet Metab 2014 Aug;112(4):280-5. Epub 2014 May 28 doi: 10.1016/j.ymgme.2014.05.012. PMID: 24930028Free PMC Article
Jinnah HA, Ceballos-Picot I, Torres RJ, Visser JE, Schretlen DJ, Verdu A, Laróvere LE, Chen CJ, Cossu A, Wu CH, Sampat R, Chang SJ, de Kremer RD, Nyhan W, Harris JC, Reich SG, Puig JG; Lesch-Nyhan Disease International Study Group
Brain 2010 Mar;133(Pt 3):671-89. Epub 2010 Feb 22 doi: 10.1093/brain/awq013. PMID: 20176575Free PMC Article
Torres RJ, Puig JG
Orphanet J Rare Dis 2007 Dec 8;2:48. doi: 10.1186/1750-1172-2-48. PMID: 18067674Free PMC Article
Nyhan WL
Annu Rev Med 1973;24:41-60. doi: 10.1146/annurev.me.24.020173.000353. PMID: 4575865

Therapy

Harris JC
Curr Opin Psychiatry 2018 Mar;31(2):96-102. doi: 10.1097/YCO.0000000000000388. PMID: 29227296
Guibinga GH
Adv Genet 2015;90:103-131. Epub 2015 Jul 20 doi: 10.1016/bs.adgen.2015.06.001. PMID: 26296934
Pais VM Jr, Lowe G, Lallas CD, Preminger GM, Assimos DG
Urology 2006 May;67(5):1084.e9-11. doi: 10.1016/j.urology.2005.10.057. PMID: 16698380
Nyhan WL
Annu Rev Med 1973;24:41-60. doi: 10.1146/annurev.me.24.020173.000353. PMID: 4575865
Arima M, Aoki N, Ono K
Paediatr Univ Tokyo 1970 Dec;18:25-31. PMID: 5514644

Prognosis

Cagiada M, Bottaro S, Lindemose S, Schenstrøm SM, Stein A, Hartmann-Petersen R, Lindorff-Larsen K
Nat Commun 2023 Jul 13;14(1):4175. doi: 10.1038/s41467-023-39909-0. PMID: 37443362Free PMC Article
Pearson TS, Pons R, Ghaoui R, Sue CM
Mov Disord 2019 May;34(5):625-636. Epub 2019 Mar 26 doi: 10.1002/mds.27655. PMID: 30913345
Guibinga GH
Adv Genet 2015;90:103-131. Epub 2015 Jul 20 doi: 10.1016/bs.adgen.2015.06.001. PMID: 26296934
Kulkarni ML, Sureshkumar C, George VG
Indian Pediatr 1993 Apr;30(4):537-40. PMID: 8288343
Davidson BL, Tarlé SA, Van Antwerp M, Gibbs DA, Watts RW, Kelley WN, Palella TD
Am J Hum Genet 1991 May;48(5):951-8. PMID: 2018042Free PMC Article

Clinical prediction guides

Cagiada M, Bottaro S, Lindemose S, Schenstrøm SM, Stein A, Hartmann-Petersen R, Lindorff-Larsen K
Nat Commun 2023 Jul 13;14(1):4175. doi: 10.1038/s41467-023-39909-0. PMID: 37443362Free PMC Article
Del Bene VA, Crawford JL, Gómez-Gastiasoro A, Vannorsdall TD, Buchholz A, Ojeda N, Harris JC, Jinnah HA, Schretlen DJ
Eur J Neurosci 2022 Jan;55(1):264-276. Epub 2021 Dec 6 doi: 10.1111/ejn.15512. PMID: 34738666Free PMC Article
Black SH
Curr Opin Pediatr 1994 Dec;6(6):712-6. doi: 10.1097/00008480-199412000-00018. PMID: 7849820
Jinnah HA, Gage FH, Friedmann T
Brain Res Bull 1990 Sep;25(3):467-75. doi: 10.1016/0361-9230(90)90239-v. PMID: 2292045
de Bruyn CH
Hum Genet 1976 Feb 29;31(2):127-50. doi: 10.1007/BF00296142. PMID: 765262

Recent systematic reviews

Krajewski O, Opiełka M, Urbanowicz K, Chojnowski K, Kochany P, Pawłowski K, Tomaszewska J, Peters GJ, Smoleński RT, Bełdzińska MM
Neurosci Biobehav Rev 2024 Oct;165:105847. Epub 2024 Aug 6 doi: 10.1016/j.neubiorev.2024.105847. PMID: 39117131
Deng H, Xiong BT, Wu Y, Wang W
Neurosurg Rev 2023 Jan 25;46(1):40. doi: 10.1007/s10143-023-01950-4. PMID: 36694014
Fischer JF, Mainka T, Worbe Y, Pringsheim T, Bhatia K, Ganos C
J Neurol Neurosurg Psychiatry 2020 Jul;91(7):712-719. Epub 2020 May 19 doi: 10.1136/jnnp-2019-322569. PMID: 32430438

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...