Lesch-Nyhan syndrome and its variants: examining the behavioral and neurocognitive phenotype.

PURPOSE OF REVIEW: Lesch-Nyhan Syndrome (LNS) is a metabolic disorder involving mutations in the HGPRT1 gene that result in hyperuricemia, intellectual disability, a dystonic movement disorder, and compulsive self-injury with self-mutilation. The aim of this review is to summarize recent research that documents the extended behavioral, neurologic, and neurocognitive phenotype in classic LNS, to describe milder variants of HGprt deficiency that do not self-injure and have less severe neurological and cognitive deficits, and to provide an update on treatment for associated psychiatric and behavioral disorders.

RECENT FINDINGS: Psychiatric management utilizes combined behavioral and pharmacological treatment in conjunction with protective equipment and dental management to avert self-injury. Pharmacological management focuses on stabilization of mood and anxiety management. S-adenosylmethionine (SAMe), a physiological intermediate in methylation and transsulfuration, has shown beneficial effects in carefully selected patients who can tolerate the drug. Deep brain stimulation is shown in several case reports and series to reduce or eliminate self-injury and aggression, and in some cases, modify dystonia.

SUMMARY: This review highlights progress in our understanding of the behavioral and neurocognitive phenotype of Lesch-Nyhan syndrome (HGprt deficiency) and its variants, describes psychiatric and behavioral management, and discusses prospects for new therapies.