Current understanding of Lesch-Nyhan disease and potential therapeutic targets

ABSTRACT

Introduction: Lesch–Nyhan disease (LND) is an inborn error of purine metabolism characterized by hyperuricemia, severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficit, and self-injurious behavior (SIB).

Areas covered: Current treatment for LND is reviewed based in MEDLINE bibliographic search and author experience. Uric acid overproduction can be managed by allopurinol treatment, hydration, and alkalinization. Doses must be carefully adjusted to avoid xanthine lithiasis. There are no effective therapies for motor and behavioral symptoms. Spasticity and dystonia can be managed with benzodiazepines and baclofen. Self-injurious behavior must be managed by physical restraints.

Expert opinion: There is a need for the development of new hypouricemic drugs, such as uricase or PNP inhibitors, to avoid xanthine lithiasis. None of the currently available medications for generalized dystonia are effective in LND patients, and severe dystonia remains despite treatment with various medications, either used alone or in combination.

KEYWORDS:

• HPRT
• Lesch–Nyhan
• SIB
• hyperuricemia
• dystonia

Article highlights

• LND is a rare disease with severe motor manifestations and self-injurious behavior with no effective therapy until now.

• Uric acid overproduction, associated with the disease, is effectively managed by allopurinol treatment, hydration, and alkalinization but doses must be carefully adjusted to avoid xanthine lithiasis.

• There is a need for the development of new hypouricemic drugs, such as uricase or PNP inhibitors, to avoid xanthine lithiasis

• Spasticity and dystonia can be only partially alleviated with benzodiazepines and baclofen. None of the currently available medications for generalized dystonia are effective in LND patients.

• Today, self-injurious behavior must be managed by physical restraints.

This box summarizes the key points contained in the article.

Acknowledgments

The author would like to acknowledge Professor Juan Garcia Puig for his guidance and support.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by Grants from Instituto de Salud Carlos III (ISCIII) PI15/01000, from Mutua Madrileña Foundation, and by Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII; Spain.