eMedicine Specialties > Neurology > Pediatric Neurology

Lesch-Nyhan Syndrome: Treatment & Medication

Author: H A Jinnah, MD, PhD, Professor, Departments of Neurology and Human Genetics, Emory University
Contributor Information and Disclosures

Updated: Dec 15, 2008

Treatment

Medical Care

  • The gross overproduction of uric acid must be controlled to prevent the development of urologic or articular complications. The goal is to maintain uric acid levels in the normal range. A common error is to attempt to suppress uric acid below normal levels, but this approach risks the development of oxypurine stones instead. The control of uric acid requires 2 important components. 
    • Allopurinol, which inhibits the metabolism of hypoxanthine and xanthine to uric acid by the enzyme xanthine oxidase, is generally effective in limiting hyperuricemia and its consequences. The dose is titrated with the goal of bringing serum uric acid levels into the normal range.
    • Generous hydration at all times is essential. Hydration should be increased during periods of increased fluid loss, such as a febrile illness or recurrent emesis.
    • Despite the combined use of allopurinol and generous hydration, nephrolithiasis still may occur.
  • Several medications are available to mitigate the severity of the neurological features, though no agent has proved consistently efficacious in all cases. Benzodiazepines, such as diazepam or alprazolam, reduce severity and help attenuate anxiety that may indirectly exacerbate the extrapyramidal abnormalities. Antispasticity agents such as baclofen or tizanidine also can be helpful.
  • Management of the behavioral problems, and particularly the self-injurious behavior, can be very difficult. In general, behavioral problems are best managed with a combination of behavioral modification techniques and medication. Behavioral extinction methods with positive reinforcement are most beneficial; techniques involving negative reinforcement are not helpful and may even exacerbate the behavior problems. Adjunctive medications, sometimes useful for attenuating problem behaviors, include gabapentin and carbamazepine.

Surgical Care

  • The metabolic defect does not preclude safe application of standard anesthetic or surgical procedures when indicated.
  • Dental work is perhaps the most commonly required surgical intervention in this disease. Dental extraction may be the only procedure for preventing serious tissue injury, if self-injurious biting cannot be controlled with behavioral and/or medical therapy.
  • Orthopedic intervention often is required for management of the consequences of the neurological disorder. Procedures may be required for release of contractures, reduction of subluxed joints, or stabilization of spinal deformity.
  • Nephrolithiasis may require surgical intervention for extraction of stones or relief from urogenital obstruction.
  • Recent studies have provided a promising suggestion that deep brain stimulation surgery may be useful for controlling both dystonia and self-injury. The procedure is considered experimental, and further studies are needed before the procedure can be broadly recommended because the brain targets seem to differ from those used for other disorders of dystonia or for Parkinson disease.

Consultations

  • Genetic counseling is essential for informing the family of the risk of additional children with the disorder.
  • Consultations with specialists in the motor disorder (Neurology, Physiatry) and the behavioral disorder (Psychiatry, Psychology) are nearly universally required. 
  • Surgical specialists may be required for joint complications (Orthopedics) or large kidney stones (Urology).

Diet

  • Most patients can eat a normal diet.
  • Dysphagia may be a significant problem, particularly with aging. Some patients respond to changes in the consistency of the diet, while others may require gastrostomy.

Activity

Despite their profound motor handicap, most patients prefer to remain actively engaged in their environments.

Medication

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Hypouricemic agents

These agents are used to control hyperuricemia, thereby reducing risk for nephrolithiasis, gouty arthritis, and subcutaneous tophi.


Allopurinol (Zyloprim)

Controls hyperuricemia by blocking action of xanthine oxidase, which converts xanthine and hypoxanthine into uric acid; dose titrated to lower uric acid levels to normal range.

Adult

300 mg PO qd

Pediatric

5-10 mg/kg/d PO divided bid/tid

Significantly reduces metabolism of 6-mercaptopurine and azathioprine; dose of latter 2 drugs must be reduced by approximately 75% if either is to be given concurrently with allopurinol
May reduce metabolism or elimination of cyclosporine, chlorpropamide, theophylline, and warfarin
Aluminum hydroxide may interfere with absorption

Several drugs have been associated with increased risk for severe, sometimes life-threatening, hypersensitivity reactions when given together with allopurinol; these drugs include thiazide diuretics, ampicillin, and amoxicillin
Allopurinol should not be used concurrently with uricosuric agents such as probenecid, because combined administration of these drugs increases delivery of uric acid and other oxypurines into urogenital system, increasing risk of stone formation

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Dose of allopurinol must be adjusted for renal insufficiency, which is common in patients with Lesch-Nyhan disease; patients receiving allopurinol must be hydrated generously at all times

More on Lesch-Nyhan Syndrome

Overview: Lesch-Nyhan Syndrome
Differential Diagnoses & Workup: Lesch-Nyhan Syndrome
Treatment & Medication: Lesch-Nyhan Syndrome
Follow-up: Lesch-Nyhan Syndrome
Multimedia: Lesch-Nyhan Syndrome
References
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References

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

  2. Jinnah HA, Friedmann T. Lesch-Nyhan disease and its variants. In: 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, 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. Oct 2000;463(3):309-26. [Medline].

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

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

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

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

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Further Reading

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Keywords

HPRT deficiency, hypoxanthine-guanine phosphoribosyl transferase, Kelley-Seegmiller syndrome, Lesch-Nyhan disease, overproduction of uric acid, neurologic disability, behavioral problems, hyperuricemia, nephrolithiasis with renal failure, gouty arthritis, tophi, dystonia, choreoathetosis, ballismus, spasticity, hyperreflexia, cognitive dysfunction, aggressive behaviors, impulsive behaviors, self-injurious behavior

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Contributor Information and Disclosures

Author

H A Jinnah, MD, PhD, Professor, Departments of Neurology and Human Genetics, Emory University
H A Jinnah, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, Movement Disorders Society, and Society for Neuroscience
Disclosure: Nothing to disclose.

Medical Editor

Robert Baumann, MD, Program Director, Professor, Departments of Neurology and Pediatrics, University of Kentucky
Robert Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American College of Epidemiology, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Neurology, Division of Pediatrics, Department of Pediatrics, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children
Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

 
 
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