Lesch-Nyhan Syndrome

I remember learning about Lesch-Nyhan and thinking it was fascinating early on during a college course on neurology & behavior: affected children with this X-linked disorder develop the bizarre but highly characteristic behavior of self-mutilation, intentional biting of the tongue and lips for instance. The neurologic basis for these behavioral changes is not entirely understood, but the underlying basis for the disorder has to do with uric acid metabolism: the affected gene in Lesch-Nyhan syndrome is the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) gene, which is necessary for the salvage pathway of purine synthesis for DNA. The absence of HGPRT results in elevated levels of uric acid which result in uric acid nephrolithiasis, gout, and gouty nephropathy in addition to the disturbing CNS manifestations mentioned above. The gold standard for diagnosis is discovering low levels of HGPRT enzyme activity in cultured cells from the affected individual.

A recent article in AJKD describes the use of Rasburicase to treat elevated uric acid levels in Lesch-Nyhan syndrome in an affected neonate. Rasburicase is an urate oxidase enzyme which rapidly reduces serum uric acid levels; it will be interesting to see if this reduction translates into an improvement in neurologic symptoms seen in this syndrome.