The Johns Hopkins University School of Medicine, Charlotte R. Bloomberg Children's Center, Baltimore, Maryland, USA.
Curr Opin Psychiatry. 2018 Mar;31(2):96-102. doi: 10.1097/YCO.0000000000000388.
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.
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.
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.
Lesch-Nyhan 综合征（LNS）是一种代谢紊乱，涉及 HGPRT1 基因的突变，导致高尿酸血症、智力残疾、张力障碍运动障碍以及强制性自残和自我伤害。本综述的目的是总结最近的研究，这些研究记录了经典 LNS 中扩展的行为、神经和神经认知表型，描述了不进行自我伤害且神经和认知缺陷较轻的 HGprt 缺乏症较轻变体，并提供了相关精神和行为障碍治疗的最新进展。
精神病学管理采用联合行为和药物治疗，结合防护设备和牙科管理，以避免自残。药物治疗侧重于稳定情绪和焦虑管理。S-腺苷甲硫氨酸（SAMe）是甲基化和转硫作用的生理中间产物，在能够耐受药物的精选患者中显示出有益效果。几项病例报告和系列研究表明，深部脑刺激可减少或消除自残和攻击行为，在某些情况下还可改善肌张力障碍。
本综述强调了我们对 Lesch-Nyhan 综合征（HGprt 缺乏症）及其变体的行为和神经认知表型的理解进展，描述了精神和行为管理，并讨论了新疗法的前景。
