Objective: To describe the neuropsychological features in five siblings with dopa responsive dystonia (DRD) due to autosomal dominant GCH1 related disease (AD GCH1).

Background: Although neuropsychiatric features are recognised in DRD, its association with learning, and whether it is modifiable with levodopa has not been explored in detail. Understanding this could potentially influence decisions about timing of treatment, which is usually guided by motor features in this condition.

Method: We describe five siblings with genetically proven DRD (exon 3 deletion of GCH1 gene) and a positive family history of DRD in the father and paternal grandmother. Two of them (male and female) had mainly neuropsychological and mild motor symptoms at presentation. In the three other sisters, none had neuropsychological symptoms, and two had mild motor symptoms.

Results: The second child, male, was tested at 5 years of age due to intermittent leg discomfort. At 6 years of age, concerns about learning, concentration, and behaviour led to neuropsychological assessment, which identified weaknesses in memory and attention. On the Strength and Difficulties Questionnaire (SDQ), overall impact was very high. With levodopa treatment, his physical symptoms as well as attention and concentration improved. Follow up neuropsychology assessment 3 years later showed improved, close to average, overall impact on SDQ. His younger sister had difficulties in learning and leg pains when diagnosed at 7 years. Neuropsychological assessment identified low – very low average nonverbal skills.  On starting levodopa treatment, her motor symptoms resolved and simultaneously, learning was also reported to have improved, although some concerns still remained.

Conclusion: We highlight the difficulties in learning and concentration in addition to neuropsychiatric symptoms in patients with DRD due to AD GCH1. Psychiatric symptoms are recognised in DRD, possibly related to the serotonin pathway being affected.¹ Additionally, post-mortem studies in patients with DRD have identified decreased biopterin and neopterin concentrations in the frontal cortex, potentially contributing to the impact on learning and behaviour.² It is therefore important to monitor for these non-motor symptoms, especially because, although it is difficult to be certain, there is suggestion from our experience that early treatment with levodopa may improve learning and concentration.

References: 1. Elena Antelmi, MD, Maria Stamelou, Rocco Liguori, Kailash P. Bhatia . Nonmotor Symptoms in Dopa-Responsive Dystonia. Mov Disord Clin Pract 2015 Jul 22;2(4):347-356. doi: 10.1002/mdc3.12211.

2. Wijemanne, S. & Jankovic, J. Nat. Rev. Neurol. 11, 414–424 (2015); published online 23 June 2015; doi:10.1038/nrneurol.2015.86

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/understanding-neuropsychological-features-of-dopa-responsive-dystonia-in-children/