• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report

Lesch Nyhan Syndrome


Last updated: July 20, 2018
Years published: 1986, 1990, 1995, 1996, 1998, 2000, 2001, 2009, 2012, 2015, 2018


NORD gratefully acknowledges William L. Nyhan, MD, PhD, Distinguished Professor, Pediatrics, School of Medicine, University of California San Diego, for assistance in the preparation of this report.

Disease Overview

Lesch-Nyhan syndrome is a rare inborn error of purine metabolism characterized by the absence or deficiency of the activity of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Purines are nitrogen-containing compounds found in many foods (e.g., organ meats, poultry, and legumes). In the absence of HPRT, the purines hypoxanthine and guanine are not built into nucleotides. Uric acid levels are abnormally high in people with Lesch-Nyhan syndrome and sodium urate crystals may abnormally accumulate in the joints and kidneys. Lesch-Nyhan syndrome is inherited as an X-linked recessive genetic disorder that, with rare female exceptions, most often affects males. The symptoms of Lesch-Nyhan syndrome include impaired kidney function, acute gouty arthritis, and self-mutilating behaviors such as lip and finger biting and/or head banging. Additional symptoms include involuntary muscle movements, and neurological impairment.

  • Next section >
  • < Previous section
  • Next section >


  • HGPRT deficiency
  • HPRT deficiency
  • hypoxanthine-guanine phosphoribosyl transferase deficiency
  • Lesch-Nyhan disease
  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Signs & Symptoms

The symptoms of Lesch-Nyhan syndrome may become apparent as early as six months of age. Earlier urate crystal formation, resulting from abnormally increased levels of uric acid in the urine, leads to the presence of orange colored deposits (“orange sand”) in the diapers of infants with this disorder. This may be the first manifestation of Lesch-Nyhan syndrome, but it is seldom recognized in early infancy.

Urate stones may develop in the kidneys of infants with Lesch-Nyhan syndrome as a result of excessive amounts of uric acid that are excreted as sodium urate. These stones may cause blood to appear in the urine (hematuria) and increase the risk of urinary tract infections. Urate crystals may also be found in the joints, but in general, it is not until the late teens or adulthood that untreated patients with Lesch-Nyhan syndrome experience recurring episodes of pain and swelling of the joints, just like those of adults with gout. These episodes may become progressively more frequent once they begin.

In older children with this disorder, deposits of sodium urate may collect in cartilaginous tissues in joints and in the ears; in the ears, they form visible “bulges” called tophi. This is the picture commonly known as gout.

Neurological symptoms associated with Lesch-Nyhan syndrome usually begin before the age of 12 months. These may include involuntary writhing movements of the arms and legs (dystonia) and purposeless repetitive movements (chorea) such as flexing of the fingers, raising and lowering of the shoulders, and/or facial grimacing. Infants who had previously been able to sit upright typically lose this ability. Initially, muscles may be soft (hypotonia) and lead to difficulty in holding the head in an upright position. Affected infants may fail to reach developmental milestones such as crawling, sitting or walking (developmental delay). Eventually, most children with Lesch-Nyhan syndrome experience abnormally increased muscle tone (hypertonia) and muscle rigidity (spasticity). Deep tendon reflexes are increased (hyperreflexia). Intellectual disability may also occur and is typically moderate. However, accurate evaluation of intelligence may be difficult because of poorly articulated speech (dysarthria). Some patients have normal intelligence.

The most striking feature of Lesch-Nyhan syndrome, which has been observed in approximately 85 percent of patients, is self-mutilation. These behaviors most often begin between the ages of two and three years. However, they can also develop during the first year of life or much later during childhood. Self-injurious behavior may include repeated biting of the lips, fingers, and/or hands, and repetitive banging of the head against hard objects. Some children may scratch their face repeatedly. However, individuals with Lesch-Nyhan syndrome are not insensitive to pain. Additional behavioral abnormalities include aggressiveness, vomiting, and spitting. Self-mutilating behaviors regularly lead to loss of tissue.

Children with Lesch-Nyhan syndrome may have difficulty swallowing (dysphagia) and may be difficult to feed. Vomiting is common, and most affected children are underweight for their age. Additional symptoms may include irritability or screaming. Some children with Lesch-Nyhan syndrome may also develop a rare anemia known as megaloblastic anemia. (For more information on megaloblastic anemia, see the Related Disorders section of this report.)

Another symptom of Lesch-Nyhan syndrome may be a severe muscle spasm that causes the back to arch severely and the head and heels to bend backward (opisthotonos). Affected children may also experience hip dislocation, fractures, abnormal curvature of the spine (scoliosis) and/or permanent fixation of several joints in a flexed position (contractures).

Female carriers usually do not have symptoms of the disorder, but may develop gout later in life as a result of untreated excess uric acid in the blood (hyperuricemia).

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >


The only gene known to be associated with Lesch-Nyhan syndrome is located on the X chromosome and called HPRT1. Abnormalities (mutations) in the HPRT1 gene result in the absence or deficiency of the enzyme hypoxanthine-guanine phosphoribosyl transferase (HPRT) and the abnormal accumulation of uric acid in the blood.

Lesch-Nyhan syndrome is inherited in an X-linked pattern. X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and manifest mostly in males. Females that have an abnormal gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the abnormal gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains an abnormal gene he will develop the disease.

Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.

If a male with an X-linked disorder is able to reproduce, he will pass the abnormal gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Affected populations

Lesch-Nyhan syndrome is a rare disorder that affects males. Rarely, females may be affected by the disorder. However, in most cases, females may be carriers of the disease gene, but do not exhibit any symptoms. According to one estimate, the disorder occurs at the rate of approximately one in 380,000 births in the United States.

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >


The diagnosis of Lesch-Nyhan syndrome may be confirmed by a thorough clinical evaluation, including a detailed patient history and specialized blood tests. Children with this disorder have abnormally high concentrations of uric acid in the blood. The absence of the HPRT enzyme in cells from any tissue confirms the diagnosis. Molecular genetic testing for the HPRT1 gene is available to determine the specific disease-causing mutation. Carrier testing for Lesch-Nyhan syndrome is possible using molecular genetic testing.

Prenatal diagnosis and preimplantation genetic diagnosis are possible if the disease-causing HPRT1 gene mutation has been identified in an affected family member. Prenatal diagnosis can also be done by enzyme analysis.

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Standard Therapies

The treatment of Lesch-Nyhan syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, specialists who diagnose and treat skeletal disorders (orthopedists), physical therapists, and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.

The drug allopurinol is used to control the excessive amounts of uric acid associated with Lesch-Nyhan syndrome and control symptoms associated with excessive amounts of uric acid. However, this treatment has no effect on the neurological or behavioral symptoms associated with this disorder.

When kidney stones are present, they may be treated with extracorporeal shock wave lithotripsy (ESWL). During this procedure, the patient is immersed in water and high energy shock waves are directed to the body in the area of the kidney stone. The stone dissolves into small pieces, and these fragments are passed with the urine.

No sustained treatment or drug therapy has proven uniformly effective for the treatment of the neurological problems associated with Lesch-Nyhan syndrome. Baclofen or benzodiazepines have been used to treat spasticity. Diazepam may be useful.

Individuals with Lesch-Nyhan syndrome have been reported to benefit from behavior modification techniques designed to reduce self-mutilating behaviors, but real success is unusual. Children with Lesch-Nyhan syndrome usually require physical restraint at the hips, chest, and elbows so they do not injure themselves. Elbow restraints keep the hands free. Biting of fingers and/or lips, which can lead to permanent disfigurement, may be prevented by the use of a mouth guard (oral prosthetic) or the removal of the teeth. Many affected individuals request restraints themselves. With advancing age, some affected individuals’ self-mutilating behaviors may improve or cease.

In some patients, drugs have been used to treat behavioral abnormalities associated with Lesch-Nyhan syndrome. These include Depakote (sodium valproate), Gabapentin, baclofen, and carbamazepine. Benzodiazepines may be beneficial in treating anxiety symptoms sometimes associated with Lesch-Nyhan syndrome.

Genetic counseling is recommended for families with children who have Lesch-Nyhan syndrome. Other treatment is symptomatic and supportive.

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:

For information about clinical trials sponsored by private sources, contact:

For information about clinical trials conducted in Europe, contact:

The following physician is a resource for additional information:

William L. Nyhan, M.D.
Professor of Pediatrics
School of Medicine
University of California San Diego
9500 Gilman Drive, MC0830
La Jolla, CA 92093- 0830
Phone #: 619-543-5260
e-mail: wnyhan@ucsd.edu
Home page: www.pediatrics.ucsd.edu/Pages/default.aspx

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >


Nyhan W, Barshop B, Al-Aqeel, A. Atlas of Inherited Metabolic Diseases – 3rd Edition. Hodder-Arnold, London; 2012.

Rosenberg, RN and Pascual, JM. Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease – 5th edition. Academic Press; 2015.Fauci AS, et al, eds. Harrison’s Principles of Internal Medicine, 14th Ed. New York, NY: McGraw-Hill, Inc; 1998:2165-66.

Adams, RD, et al, eds. Principles of Neurology. 6th ed. New York, NY: McGraw-Hill, Companies; 1997:973-74.

Behrman RE, ed. Nelson Textbook of Pediatrics, 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996:405-06.

Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:1115-16.

Scriver CR, et al, eds. The Metabolic and Molecular Basis of Inherited Disease. 7th Ed. New York, NY; McGraw-Hill Companies, Inc; 1995:1664-66.

Kaplan HI, Sadock BJ, eds. Comprehensive Textbook of Psychiatry. 5th Ed.: Baltimore, MD: Williams & Wilkins; 1989:575.

Dolcetta D, Parmigiani P, Salmaso L, Bernardelle R, Cesari U, Andrighetto G, Baschirotto G, Nyhan WL, Hladnik U. Quantitative evaluation of the clinical effects of S-Adenosylmethionine on mood and behavior in Lesch-Nyhan patients. Nucleosides, Nucleotides and Nucleic Acids. 2013;32:174 188.

Jinnah HA, et al. The spectrum of mutations causing HPRT deficiency: An update. Nucleosides, Nucleotides and Nucleic Acids.2004;23:1153-1160.

Visser JE, et al. Lesch-Nyhan disease and the basal ganglia. Brain Res Brain Res Rev. 2000;32:449-75.

Olson L, et al. A review of behavioral treatments used for Lesch-Nyhan syndrome. Behav Modif. 2000;24:202-22.

De Gregorio L, et al. An unexpected affected female patient in a classical Lesch-Nyhan family. Mol Genet Metab. 2000;69:263-68.

Sponseller PD, et al. Orthopedic problems in Lesch-Nyhan syndrome. J Pediatr Orthop. 1999;19:596-602.

Matthews WS, et al. Cognitive functioning in Lesch-Nyhan syndrome: a 4-year follow-up study. Dev Med Child Neurol. 1999;41:260-62.

Nyhan WL, et al. New approaches to understanding Lesch-Nyhan disease. N Engl J Med. 1996;334:1602-04.

Ernst M, et al. Presynaptic dopaminergic deficits in Lesch-Nyhan disease. N Engl J Med. 1996;334:1568-72.

Jenkins EA, et al. Lesch-Nyhan syndrome presenting with renal insufficiency in infancy and transient neonatal hypothyroidism. Br J Rheumatol. 1994;33:392-96.

Anderson LT, et al. Self-injury in Lesch-Nyhan disease. J Autism Dev Disord. 1994;24:67-81.

Sugahara T, et al. Lesch-Nyhan syndrome: successful prevention of lower lip ulceration caused by self-mutilation by use of mouth guard. Int J Oral Maxillofac Surg. 1994;23:37-38.

Evans J, et al. Lesch-Nyhan syndrome and the lower lip guard. Oral Surg Oral Med Oral Pathol. 1993;76:437-40.

Anderson LT, et al. Cognitive abilities of patients with Lesch-Nyhan disease. J Autism Dev Disord. 1992;22:189-203.

Hatanaka T, et al. Lesch-Nyhan syndrome with delayed onset of self-mutilation: hyperactivity of interneurons at the brainstem and blink reflex. Acta Neurol Scand. 1990;81:184-87.

Nyhan WL, O’Neill JP, Jinnah HA, et al. Lesch-Nyhan Syndrome. 2000 Sep 25 [Updated 2014 May 15]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1149/ Accessed July 12, 2018.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Hypoxanthine Guanine Phosphoribosyltransferase 1; HPRT1. Entry No: 308000. Last Edited 09/27/2017. Available at: http://omim.org/entry/308000 Accessed July 12, 2018.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Lesch-Nyhan syndrome; LNS. Entry No: 300322. Last Edited 09/01/2017. Available at: http://omim.org/entry/300322 Accessed July 12, 2018.

  • < Previous section
  • Next section >

Programs & Resources

RareCare® Assistance Programs

NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.

Additional Assistance Programs

MedicAlert Assistance Program

NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.

Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/

Rare Disease Educational Support Program

Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.

Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/

Rare Caregiver Respite Program

This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.

Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/

Patient Organizations

National Organization for Rare Disorders