LESCH-NYHAN SYNDROME

Lesch Nyhan syndrome (LNS) is an inborn error of purine metabolism characterized by hyperuricemia, severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficits and self-injurious behavior. The syndrome is associated with complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity. Partial HGPRT deficiency is termed Lesch Nyhan variants and includes patients with HGPRT-related gout and a variable degree of neurological involvement but without the complete syndrome. Uric acid overproduction is present in all HGPRT-deficient patients and is associated with lithiasis and gout. Megaloblastic anemia is also associated with the disease. Inheritance of HGPRT deficiency is X-linked recessive, and thus males are generally affected and heterozygous females are carriers (usually asymptomatic). Uric acid overproduction can be managed by allopurinol treatment. Doses must be carefully adjusted to avoid xanthine lithiasis. The importance of new hypouricemic drugs such as uricase and febuxostat needs to be established. The lack of a precise understanding of the neurological dysfunction has precluded the development of useful therapies. Spasticity, when present, and dystonia can be managed with benzodiazepines and gamma-aminobutyric acid (GABA) inhibitors such as baclofen. Self-injurious behavior must be managed by a combination of physical restraints, behavioral and pharmaceutical treatments. New agonists and antagonists of adenosine and dopamine receptors may play a role in LNS treatment.