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Lesch-Nyhan Disease Medication

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

Medication Summary

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.

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Hypouricemic Agents

Class Summary

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

Allopurinol (Zyloprim)

 

Allopurinol controls hyperuricemia by blocking action of xanthine oxidase, which converts xanthine and hypoxanthine into uric acid. The dose is titrated to lower uric acid levels to a normal range.

Febuxostat (Uloric)

 

Febuxostat is a potential alternative to allopurinol. Like allopurinol, febuxostat is a xanthine oxidase inhibitor that prevents uric acid production and lowers elevated serum uric acid levels. Unlike allopurinol, it is a thiazolecarboxylic acid derivative, not a purine base analog. Febuxostat physically blocks the channel to the molybdenum-pterin active site of xanthine oxidase and is metabolized by liver oxidation and glucuronidation.

Common adverse events include upper respiratory tract infections, arthralgias, diarrhea, headache, and liver function abnormalities. Atrioventricular block or atrial fibrillation in 5% and cholecystitis in 2% have also been reported.

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Benzodiazepines

Class Summary

Agents from this class may mitigate the severity of the neurologic features of the disease. Benzodiazepines, such as diazepam or alprazolam, reduce severity and help attenuate anxiety that may indirectly exacerbate the extrapyramidal abnormalities. Additionally, adjunctive medications including benzodiazepines and gabapentin are sometimes useful for attenuating problem behaviors.

Lorazepam (Ativan)

 

Lorazepam is a sedative-hypnotic of the benzodiazepine class that has a rapid onset of effect and a relatively long half-life. By increasing the action of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, it may depress all levels of the central nervous system (CNS), including the limbic system and reticular formations. Lorazepam is suitable for patients who need to be sedated for longer than 24 hours.

Diazepam (Valium, Diastat)

 

Diazepam depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.

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Anticonvulsants, Other

Class Summary

Agents from this class may mitigate the severity of the neurologic features of the disease. Adjunctive medications, sometimes useful for attenuating problem behaviors, include gabapentin and benzodiazepines.

Gabapentin (Neurontin)

 

Gabapentin, a membrane stabilizer, is a structural analogue of the inhibitory neurotransmitter GABA, although, paradoxically, it is thought not to exert an effect on GABA receptors. It appears to exert its action via the alpha(2)delta1 and alpha(2)delta2 auxiliary subunits of voltage-gaited calcium channels. Gabapentin is used to manage pain and provide sedation in neuropathic pain.

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Skeletal Muscle Relaxants

Class Summary

Agents from this class may mitigate the severity of the neurologic features of the disease. Muscle relaxants are commonly used to treat muscle pain, but they must be used cautiously because of sedation and because of the addictive potential of some of the medications in this category of drugs.

Baclofen (Lioresal, Gablofen)

 

Baclofen may induce the hyperpolarization of afferent terminals and inhibit monosynaptic and polysynaptic reflexes at the spinal level.

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Contributor Information and Disclosures
Author

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.

Acknowledgements

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

References
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  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].

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  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].

 
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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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