Objective: To evaluate the role for levodopa in patients with ataxia telangiectasia like disorder (ATLD) who have a compound heterozygous mutation in MRE11.

Background: Early-onset cerebellar ataxia with cerebellar atrophy can be seen in Ataxia Telangiectasia as well as in less well-known conditions such as MRE11-related ATLD. A positive response to levodopa in patients with homozygous mutations in MRE11 has been rarely reported [1]. To our knowledge, there is no study that characterizes the response to levodopa in patients with a compound heterozygous mutation in MRE11.

Method: This is a case report on the clinical presentation of a 20-year-old female with working diagnosis of ATLD.

Results: A 20-year-old female presented with a history of unsteady gait, speech issues, intellectual disability, and poor fine motor skills/hand eye coordination that started at age 16. Physical exam was notable for dysarthria, hypermetric eye movements with sustained nystagmus at end lateral gaze and macro-saccadic oscillations at rest, mildly increased muscle tone, mildly slowed rapid alternating movements, diffuse hyperreflexia, mildly ataxic finger-to-nose testing, and a wide-based high steppage gait. Brain MRI revealed mild to moderate cerebellar atrophy without abnormalities in the brainstem or cerebral hemispheres. Over the course of the next 5 years, she experienced a progressive deterioration and could no longer walk or dress herself without assistance, had dystonia of her right index finger, and had a few episodes of falling backwards. Exome sequencing showed a paternally inherited heterozygous variant in MRE11 (classified as pathogenic) and a maternally inherited heterozygous variant in MRE11 (classified as of uncertain significance). Given compound heterozygosity for MRE11, chromosome instability testing was sent that was negative but does not rule out an MRE11 deficiency. The patient was started on carbidopa-levodopa. Over the last few months, she has been able to walk while holding onto a wall or desk without big falls or recent head trauma and her speech is still mildly dysarthric but stable.

Conclusion: Movement disorder that responds to levodopa has been described in patients with ATLD due to homozygous variants in MRE11 [1]. This case suggests that patients with compound heterozygous mutations may also benefit from levodopa and that a levodopa trial can be considered when clinically assessing patients with ataxia.

References: [1] Ser, M. H., Tekgül, Ş., Gündüz, A., Kızıltan, M. E., Kızıltan, G., & Başak, A. N. (2020). Ataxia telangiectasia like disorder: Another dopa-responsive disorder look-alike?. Parkinsonism & related disorders, 74, 22-24.

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/dopa-responsive-ataxia-with-compound-heterozygous-variants-in-mre11/