Self-Mutilation in Lesch-Nyhan Disease Is Caused by Dopaminergic Denervation

Goldstein, Menek; Anderson, Lowell T.; Reuben, Richard N.; Dancis, Joseph

doi:10.1016/s0140-6736(85)91107-9

Cited by 87 publications

(26 citation statements)

References 3 publications

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“…An alternate hypothesis on the role of dopamine in LNS is that the dopaminergic deficiency results in increased sensitization of dopamine receptors in the remaining dopaminergic cells, and that this sensitization is the underlying cause of the neurobehavioral phenotypes found in LNS [Goldstein et al, 1985]. This hypothesis is consistent with behavioral models of LNS, such as 6-OHDA-lesioned rats, which appear to self-injure in response to an increase in dopaminergic production [Breese et al, 1984[Breese et al, , 2005.…”

Section: Dopaminesupporting

confidence: 54%

“…SCH-12679, a D1 receptor antagonist was investigated in non-LNS aggressive individuals [Itil et al, 1972], and its effect was hypothesized to be translatable to LNS patients, but the study was halted due to adverse effects on LNS patients [Albert et al, 1977;Elie et al, 1980]. Fluphenazine, a D1 and D2 receptor antagonist, has shown improvements in self-biting [Goldstein et al, 1985;Jankovic et al, 1988;Gualtieri and Schroeder, 1989], but the use of this drug was again discontinued because of severe side effects of akithesia and tardive dyskinesia [Gualtieri and Schroeder, 1989]. The antipsychotics haloperidol, pimozide, risperidone, and tetrabenazine primarily antagonize the D2 receptor with some D1 receptor binding.…”

Section: Dopaminementioning

confidence: 99%

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Lesch-Nyhan Syndrome: Models, Theories, and Therapies

et al. 2016

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Lesch-Nyhan syndrome (LNS) is a rare X-linked disorder caused by mutations in HPRT1, an important enzyme in the purine salvage pathway. Symptoms of LNS include dystonia, gout, intellectual disability, and self-mutilation. Despite having been characterized over 50 years ago, it remains unclear precisely how deficits in hypoxanthine and guanine recycling can lead to such a profound neurological phenotype. Several studies have proposed different hypotheses regarding the etiology of this disease, and several treatments have been tried in patients, though none have led to a satisfactory explanation of the disease. New technologies such as next-generation sequencing, optogenetics, genome editing, and induced pluripotent stem cells provide a unique opportunity to map the precise sequential pathways leading from genotype to phenotype.

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Section: Dopaminesupporting

confidence: 54%

Section: Dopaminementioning

confidence: 99%

Lesch-Nyhan Syndrome: Models, Theories, and Therapies

et al. 2016

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“…Some investigators have suggested that neurotransmitters or neuroreceptors, such as serotonin or dopamine, may be involved in the pathogenesis of this behavior. 11,13 In individuals with spinal cord disorders, selfinjurious behavior may represent a response to dysesthesia. In one of the reports of self-injurious behavior in a child with myelomeningocele, symptoms consistent with dysesthesia were present.…”

Section: Discussionmentioning

confidence: 99%

Self-injurious behavior in children and adolescents with spinal cord injuries

2002

Spinal Cord

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Study design: A case report of self-injurious behavior in four children and adolescents with spinal cord injuries (SCI). Objectives: To report a relatively unusual complication of pediatric-onset SCI, focusing on the potential role that dysesthesia may play in self-injurious behavior. Setting: A Spinal Cord Injury Program in a Children's Hospital in Chicago that serves children from midwestern and south-central United States of America. Method: Case reports and literature review. Results: Case reports are presented of four children or adolescents with SCI who exhibited self-injurious behavior. Two of the subjects had symptoms consistent with dysesthesia. The self-injurious behavior in these two subjects and a very young child responded to treatment with anticonvulsants. The self-injurious behavior in the fourth patient was probably the result of poor technique of using his mouth to move his hands, which responded to conservative management including education, occupational therapy and gloves. Conclusion: Self-injurious behavior is a relatively unusual complication of pediatric onset SCI, and may be a manifestation of dysesthesia and be responsive to treatment with anticonvulsants.

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“…Trials with 5-HTP (a serotonin agonist), fluoxetine (a serotonin reuptake inhibitor), naltrexone (an opiate antagonist) and fluphenazine (a dopamine antagonist) have shown either no effect or produced reductions in SIB for only short periods of time (Nyhan et al, 1980;Anderson et al, 1976;Nyhan, 1994). Interestingly, Goldstein et al, (1985) found fluphenazine completely eliminated SIB in one boy aged 20 months (whose SIB had just started) whereas in another child, aged 15, fluphenazine actually increased levels of SIB. More studies of treatments that are begun early in the child's life are clearly needed.…”

mentioning

confidence: 99%