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Lesch-Nyhan Disease Clinical Presentation

  • Author: H A Jinnah, MD, PhD; Chief Editor: Amy Kao, MD  more...
Updated: Dec 14, 2015


Most patients with classic Lesch-Nyhan disease present at age 3-12 months with delayed motor development, most commonly hypotonia or failure to reach normal motor milestones. Between ages 6 and 18 months, abnormal involuntary movements indicative of extrapyramidal dysfunction become more prominent; some patients also develop corticospinal signs. Patients may often receive a diagnosis of cerebral palsy. After an initial period of progression that may last until age 3-6 years, motor disability does not continue to progress.[3]

A smaller number of patients present with complications related to the overproduction of uric acid. Sometimes there is a history of "orange sand" in the diapers, which is caused by uric acid crystalluria and microhematuria. Other patients may present with renal failure or frank hematuria, resulting from nephrolithiasis. A few patients may present with gout.

Though self-injurious behavior is rarely the presenting feature of the illness, it eventually develops in all cases. The emergence of the behavior often provides the essential clue to the diagnosis in a case with known developmental delay or hyperuricemia. Self-injury does not occur in the Lesch-Nyhan variants. These patients present with signs of motor delay or consequences of overproduction of uric acid.[4]


Physical Examination

The most salient feature of the general physical examination in classic cases of Lesch-Nyhan disease is growth retardation. Somatic growth is affected more than head circumference; bone age is affected only slightly. Testicular atrophy is common. Puberty is often delayed or absent. There may be evidence of tissue disfigurement, such as scarring of the lips or hands.

Neurologically, cognitive function is impaired, with average intelligence quotient (IQ) values of approximately 60. Basic sensory functions are intact, though motor function is severely compromised. All patients exhibit severe generalized dystonia. Some also exhibit other features, including choreoathetosis, opisthotonic spasms, and ballismus. Approximately 25% also display hyperreflexia and ankle clonus. The severity of the neurologic dysfunction precludes normal ambulation, and all patients are wheelchair bound.

Behavioral problems are also prominent. Frequent attempts toward self-injury may be evident (see the images below). Partial amputations of the fingers, lips, tongue, or oral mucosa, resulting from self-biting, are common. Serious injuries or scarring from repetitive self-abrasion or hitting also may result. In addition to self-injurious behavior, many patients display compulsive behaviors that often are interpreted as signs of aggression. These include hitting, spitting, coprolalia, copropraxia, and manipulative behavior.

A small portion of the lower lip has been disfigur A small portion of the lower lip has been disfigured by persistent self-biting.
The distal portions of several fingers are shorten The distal portions of several fingers are shortened by prior uncontrolled self-biting.
Contributor Information and Disclosures

H A Jinnah, MD, PhD Professor, Departments of Neurology, Human Genetics, and Pediatrics, Emory University School of Medicine

H A Jinnah, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, International Parkinson and Movement Disorder Society, Society for Neuroscience

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock from Cellectar Biosciences; have stock from Varian medical systems; have stock from Express Scripts.


Robert J Baumann, MD Professor of Neurology and Pediatrics, Department of Neurology, University of Kentucky College of Medicine

Robert J Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, and Child Neurology Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

  1. Lesch M, Nyhan WL. A familial disorder of uric acid metabolism and central nervous system function. Am J Med. 1964 Apr. 36:561-70. [Medline].

  2. Jinnah HA, Friedmann T. Lesch-Nyhan disease and its variants. Scriver CR, Sly WS, Childs B, Beaudet AL, et al, eds. The Molecular and Metabolic Bases of Inherited Disease. 6th ed. New York, NY: McGraw-Hill; 2000. Chapter 107.

  3. Jinnah HA, Visser JE, Harris JC, et al. Delineation of the motor disorder of Lesch-Nyhan disease. Brain. 2006 May. 129(Pt 5):1201-17. [Medline].

  4. Jinnah HA, Ceballos-Picot I, Torres RJ, Visser JE, Schretlen DJ, Verdu A, et al. Attenuated variants of Lesch-Nyhan disease. Brain. 2010 Feb 22. [Medline]. [Full Text].

  5. Visser JE, Bar PR, Jinnah HA. Lesch-Nyhan disease and the basal ganglia. Brain Res Brain Res Rev. 2000 Apr. 32(2-3):449-75. [Medline].

  6. Jinnah HA, De Gregorio L, Harris JC, et al. The spectrum of inherited mutations causing HPRT deficiency: 75 new cases and a review of 196 previously reported cases. Mutat Res. 2000 Oct. 463(3):309-26. [Medline].

  7. Fu R, Jinnah HA. Genotype-Phenotype Correlations in Lesch-Nyhan Disease: Moving Beyond the Gene. J Biol Chem. 2011 Dec 7. [Medline].

  8. Fu R, Ceballos-Picot I, Torres RJ, Larovere LE, et al. Genotype-phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder. Brain. 2013 Aug 22. [Medline].

  9. Neychev VK, Jinnah HA. Sudden death in Lesch-Nyhan disease. Dev Med Child Neurol. 2006 Nov. 48(11):923-6. [Medline].

  10. Alford RL, Redman JB, O'Brien WE, et al. Lesch-Nyhan syndrome: carrier and prenatal diagnosis. Prenat Diagn. 1995 Apr. 15(4):329-38. [Medline].

  11. Nyhan WL, Vuong LU, Broock R. Prenatal diagnosis of Lesch-Nyhan disease. Prenat Diagn. 2003 Oct. 23(10):807-9. [Medline].

  12. Schretlen DJ, Varvaris M, Ho TE, Vannorsdall TD, Gordon B, Harris JC, et al. Regional Brain Volume Abnormalities in Lesch-Nyhan Disease and its Variants. Lancet Neurology. 2013.

  13. Deon LL, Kalichman MA, Booth CL, Slavin KV, Gaebler-Spira DJ. Pallidal Deep-Brain Stimulation Associated With Complete Remission of Self-injurious Behaviors in a Patient With Lesch-Nyhan Syndrome: A Case Report. J Child Neurol. 2011 Sep 22. [Medline].

Purine metabolic pathways.
A small portion of the lower lip has been disfigured by persistent self-biting.
The distal portions of several fingers are shortened by prior uncontrolled self-biting.
The HPRT gene has 9 exons, with the coding region depicted as light gray boxes. Genetic mutations in Lesch-Nyhan disease and its variants are heterogenous and include point mutations leading to amino acid substitution (yellow circles), point mutations leading to premature stop (red squares), insertions (blue triangles), deletions (white lines), and other more complex changes (not shown).
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