Neuropsychiatric symptoms and intelligence quotient in autosomal dominant Segawa disease

Abstract

Segawa disease is a rare dystonia due to autosomal dominant guanosine triphosphate cyclohydrolase I (adGTPCH) deficiency, affecting dopamine and serotonin biosynthesis. Recently, the clinical phenotype was expanded to include psychiatric manifestations, such as depression, anxiety, obsessive-compulsive disorder, and sleep disturbances. Although cognitive and neuropsychiatric symptoms may be attributable to dopamine deficiency in the prefrontal cortex and frontostriatal circuitry, intelligence is considered normal in Segawa disease. Our aim was to investigate neuropsychiatric symptoms and intelligence quotients (IQ) in a series of individuals with adGTPCH deficiency. The assessment included a structured clinical interview following the DSM-IV-TR's guidelines, Beck's Depression Inventory, the State-Trait Anxiety Inventory, the Maudsley Obsessive-Compulsive Questionnaire, the Barratt Impulsiveness Scale-11 (BIS-11), the Oviedo Sleep Questionnaire, the Pittsburgh Sleep Quality Index, and the Wechsler Adult Intelligence Scale-Third Edition. Equivalent tests were applied to pediatric patients as appropriate for their age group. Fourteen patients with adGTPCH deficiency were evaluated (seven adult and seven pediatric patients). Depression, anxiety, and obsessive-compulsive symptoms were not more common than expected in the general population. However, the seven adults showed impulsivity in the BIS-11; nine individuals had an IQ in the range of borderline intellectual functioning to mild mental retardation, and sleep disturbances were found in four individuals. We found no differences between these results and the motor impairment. In conclusion, our findings would suggest that cognitive impairment, and impulsivity in adults, may be associated with Segawa disease.

Dopa-responsive dystonia—clinical and genetic heterogeneity

“…48 Intelligence is usually considered to be unimpaired in patients with GTP-CH-I deficiency, but one study showed that 64% of patients with the condition had IQ scores significantly below average (interquartile range , and were classed as having borderline intellectual functioning. 49 Autopsies have thus far provided no evidence of degeneration in the striatum or substantia nigra in patients with the classic presentation of DRD with GTP-CH-I deficiency. 50,51 However, dopamine levels were reduced in the nigrostriatal terminals (92% reduction in the putamen and 82% reduction in the caudate) relative to healthy control levels, but were preserved in the pars compacta of the substantia nigra.…”

Dyskinesias as a Limiting Factor in the Treatment of Segawa Disease

“…The ethics committee of University Hospital Reina Sofía approved the study. The neuropsychiatric features of the index case and her mother were previously reported (Family B)[6], as was the phenylalanine loading in the index case (case 14) [7], although at the time of those reports no mutation had been identified. The index case was born to healthy parents and presented with congenital torticollis that resolved completely by one year of age with physical therapy.…”

Non-motor symptoms in genetically defined dystonia: Homogenous groups require systematic assessment

“…Sleep disturbance was identified in two adults and two children. In the adults this took the form of chronic sleep insufficiency (insomnia (n ¼ 1) and insufficient rest (n ¼ 1)) and in children was manifested as sleepwalking [14].…”

“…All individuals were receiving dopaminergic therapy at the time of assessment [13]. Two studies have sought to address psychiatric, cognitive and sleep disturbance symptoms [14,15]. The first examined 7 adults and 7 children.…”