Current understanding of Lesch-Nyhan disease and potential therapeutic targets

Abstract

ABSTRACTIntroduction: 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.