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Lesch-Nyhan syndrome(LNS)

MedGen UID:
9721
Concept ID:
C0023374
Disease or Syndrome
Synonyms: Choreoathetosis self-mutilation syndrome; Complete HPRT deficiency; Complete hypoxanthine-guanine phosphoribosyltransferase deficiency; Deficiency of guanine phosphoribosyltransferase; Deficiency of hypoxanthine phosphoribosyltransferase; Hypoxanthine guanine phospho-ribosyltransferase 1 deficiency; Hypoxanthine guanine phosphoribosyltransferase deficiency; hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency; Juvenile gout, choreoathetosis, mental retardation syndrome; Juvenile hyperuricemia syndrome; Lesch-Nyhan Disease; LNS; Primary hyperuricemia syndrome; Total HPRT deficiency; Total hypoxanthine-guanine phosphoribosyl transferase deficiency; X-linked hyperuricemia; X-linked primary hyperuricemia; X-linked uric aciduria enzyme defect
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
425042
Concept ID:
CN001297
Genetic Function
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.
SNOMED CT: Lesch-Nyhan syndrome (10406007); Complete HGPRT deficiency (10406007); Choreoathetosis self-mutilation syndrome (10406007); Total HGPRT deficiency (10406007); Deficiency of hypoxanthine-guanine phosphoribosyltransferase (124275001); Deficiency of guanine phosphoribosyltransferase (124275001); Deficiency of IMP pyrophosphorylase (124275001); Deficiency of hypoxanthine phosphoribosyltransferase (124275001); 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)
 
Gene: HPRT1
Cytogenetic location: Xq26.2-26.3
OMIM: 300322

Disease characteristics

Excerpted from the GeneReview: Lesch-Nyhan Syndrome
Lesch-Nyhan syndrome is characterized by motor dysfunction that resembles cerebral palsy, cognitive and behavioral disturbances, and uric acid overproduction (hyperuricemia). The most common presenting features, hypotonia and developmental delay, are evident by age three to six months. Affected children are delayed in sitting and most never walk. Within the first few years, extrapyramidal involvement (e.g., dystonia, choreoathetosis, opisthotonos) and pyramidal involvement (e.g., spasticity, hyperreflexia, extensor plantar reflexes) become evident. Cognitive impairment and behavioral disturbances emerge between ages two and three years. Persistent self-injurious behavior (biting the fingers, hands, lips, and cheeks; banging the head or limbs) is a hallmark of the disease. Overproduction of uric acid may lead to deposition of uric acid crystals or calculi in the kidneys, ureters, or bladder. Gouty arthritis may occur later in the disease. Related disorders with less severe manifestations include hyperuricemia with neurologic dysfunction but no self-injurious behavior and hyperuricemia alone, sometimes with acute renal failure. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
William L Nyhan  |  J Patrick O'Neill  |  Hyder A Jinnah, et. al.   view full author information

Additional description

From GHR
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.  http://ghr.nlm.nih.gov/condition/lesch-nyhan-syndrome

Clinical features

Testicular atrophy
MedGen UID:
504310
Concept ID:
CN000030
Finding
Wasting (atrophy) of the testicle (the male gonad) manifested by a decrease in size and potentially by a loss of fertility.
Nephrolithiasis
MedGen UID:
504597
Concept ID:
CN000736
Finding
The presence of calculi (stones) in the kidneys.
Spasticity
MedGen UID:
504771
Concept ID:
CN001152
Finding
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Motor delay
MedGen UID:
504779
Concept ID:
CN001164
Finding
A type of `Developmental delay` (HP:0001263) characterized by a delay in acquiring motor skills.
Dystonia
MedGen UID:
504804
Concept ID:
CN001220
Finding
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.
Abnormality of extrapyramidal motor function
MedGen UID:
505080
Concept ID:
CN001873
Finding
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).
Gout (feet)
MedGen UID:
504977
Concept ID:
CN001676
Finding
`Gout` (HP:0001997) affecting the `Metatarsophalangeal joint of big toe`.
Megaloblastic anemia
MedGen UID:
504989
Concept ID:
CN001708
Finding
Anemia characterized by the presence of erythroblasts that are larger than normal (megaloblasts).
Gout (feet)
MedGen UID:
504977
Concept ID:
CN001676
Finding
`Gout` (HP:0001997) affecting the `Metatarsophalangeal joint of big toe`.
Muscular hypotonia
MedGen UID:
504768
Concept ID:
CN001147
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.

Professional guidelines

PubMed

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. [Epub ahead of print] PMID: 20648055Free PMC Article
Schaefer GB, Mendelsohn NJ; Professional Practice and Guidelines Committee
Genet Med 2008 Apr;10(4):301-5. doi: 10.1097/GIM.0b013e31816b5cc9. PMID: 18414214Free PMC Article

Recent clinical studies

Etiology

Fu R, Ceballos-Picot I, Torres RJ, Larovere LE, Yamada Y, Nguyen KV, Hegde M, Visser JE, Schretlen DJ, Nyhan WL, Puig JG, O'Neill PJ, Jinnah HA; Lesch-Nyhan Disease International Study Group
Brain 2014 May;137(Pt 5):1282-303. Epub 2013 Aug 22 doi: 10.1093/brain/awt202. [Epub ahead of print] PMID: 23975452Free PMC Article
Schretlen DJ, Varvaris M, Ho TE, Vannorsdall TD, Gordon B, Harris JC, Jinnah HA
Lancet Neurol 2013 Dec;12(12):1151-8. PMID: 24383089Free PMC Article
Peters TJ
J R Coll Physicians Edinb 2013;43(2):161-8. doi: 10.4997/JRCPE.2013.215. PMID: 23734360
Jinnah HA, Sabina RL, Van Den Berghe G
Handb Clin Neurol 2013;113:1827-36. doi: 10.1016/B978-0-444-59565-2.00052-6. PMID: 23622405
Arhakis A, Topouzelis N, Kotsiomiti E, Kotsanos N
Dent Traumatol 2010 Dec;26(6):496-500. doi: 10.1111/j.1600-9657.2010.00930.x. PMID: 21078074

Diagnosis

Doucet BP, Jegatheesan D, Burke J
BMJ Case Rep 2013 Dec 10;2013 doi: 10.1136/bcr-2013-201997. PMID: 24326440
Torres RJ, Puig JG, Ceballos-Picot I
Eur J Hum Genet 2013 Oct;21(10) Epub 2013 Jan 16 doi: 10.1038/ejhg.2012.304. [Epub ahead of print] PMID: 23321622Free PMC Article
Sapag A, Frischling E, Laborde H
Joint Bone Spine 2013 Jan;80(1):93-5. Epub 2012 Sep 19 doi: 10.1016/j.jbspin.2012.06.020. [Epub ahead of print] PMID: 22999896
Sharma S, Jiménez RT, Aneja S, Garcia MG, Sethi GR
Indian J Pediatr 2012 Nov;79(11):1520-2. Epub 2011 Dec 20 doi: 10.1007/s12098-011-0657-9. [Epub ahead of print] PMID: 22183764
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. [Epub ahead of print] PMID: 20648055Free PMC Article

Therapy

Doucet BP, Jegatheesan D, Burke J
BMJ Case Rep 2013 Dec 10;2013 doi: 10.1136/bcr-2013-201997. PMID: 24326440
Dolcetta D, Parmigiani P, Salmaso L, Bernardelle R, Cesari U, Andrighetto G, Baschirotto G, Nyhan WL, Hladnik U
Nucleosides Nucleotides Nucleic Acids 2013;32(4):174-88. doi: 10.1080/15257770.2013.774012. PMID: 24001191
Kállay K, Liptai Z, Benyó G, Kassa C, Goda V, Sinkó J, Tóth A, Kriván G
Metab Brain Dis 2012 Jun;27(2):193-6. Epub 2012 Feb 17 doi: 10.1007/s11011-012-9279-9. [Epub ahead of print] PMID: 22350962
Oh MM, Ham BK, Kang SH, Bae JH, Kim JJ, Yoo KH, Yoon DK, Moon du G
Urol Res 2011 Oct;39(5):417-9. Epub 2011 Feb 18 doi: 10.1007/s00240-011-0364-z. [Epub ahead of print] PMID: 21331772
Roche A, Pérez-Dueñas B, Camacho JA, Torres RJ, Puig JG, García-Cazorla A, Artuch R
Am J Kidney Dis 2009 Apr;53(4):677-80. Epub 2008 Nov 6 doi: 10.1053/j.ajkd.2008.09.011. [Epub ahead of print] PMID: 18992978

Prognosis

Romero Maroto M, Ruiz Duque C, Vincent G, Garcia Recuero I, Romance A
J Clin Pediatr Dent 2014 Spring;38(3):247-9. PMID: 25095320
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. [Epub ahead of print] PMID: 20648055Free PMC Article
Arhakis A, Topouzelis N, Kotsiomiti E, Kotsanos N
Dent Traumatol 2010 Dec;26(6):496-500. doi: 10.1111/j.1600-9657.2010.00930.x. PMID: 21078074
Fujimori S, Davidson BL, Kelley WN, Palella TD
J Clin Invest 1989 Jan;83(1):11-3. doi: 10.1172/JCI113846. PMID: 2910902Free PMC Article
Mizuno T
Neuropediatrics 1986 Aug;17(3):158-61. doi: 10.1055/s-2008-1052518. PMID: 3762872

Clinical prediction guides

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. [Epub ahead of print] PMID: 20648055Free PMC Article
Pralong E, Pollo C, Coubes P, Bloch J, Roulet E, Tétreault MH, Debatisse D, Villemure JG
Neurophysiol Clin 2005 Nov-Dec;35(5-6):168-73. Epub 2006 Jan 18 doi: 10.1016/j.neucli.2005.12.004. [Epub ahead of print] PMID: 16530134
Saito Y, Hanaoka S, Fukumizu M, Morita H, Ogawa T, Takahashi K, Ito M, Hashimoto T
Brain Dev 1998 Dec;20(8):579-85. PMID: 9865540
Lynch BJ, Noetzel MJ
Pediatr Neurol 1991 Sep-Oct;7(5):389-91. PMID: 1764145
Fujimori S, Davidson BL, Kelley WN, Palella TD
J Clin Invest 1989 Jan;83(1):11-3. doi: 10.1172/JCI113846. PMID: 2910902Free PMC Article

Recent systematic reviews

Van Praag HM, Plutchik R, Conte H
Ann N Y Acad Sci 1986;487:150-67. PMID: 2436530

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