Category: Rare Neurometabolic Movement Disorders
Objective: To characterize the movement disorder spectrum in mitochondrial aminoacyl-tRNA synthetase (m-aaRS)defects.
Background: m-aaRS disorders are an increasingly recognized genetic conditions demonstrating marked phenotypic pleiotropy, ranging from neurodevelopmental to neurodegenerative phenotypes.
Method: We performed a retrospective chart review of children 1–18 years with m-aaRS disorders, evaluated in pediatric neurology, movement disorder & metabolic clinics across 2 tertiary care centers in Canada-India, 2023-2025. Clinical features, neuroimaging & genetic findings were analyzed.
Results: Six children were identified with m-aaRS defects due to variants in CARS2, WARS2, PARS2, TARS2 & EARS2.
A 9-year-old girl presented with cortical myoclonus, gait ataxia, hand dystonia, cognitive decline & hearing loss. Family history revealed a similarly affected brother with rapidly progressive disease- generalized myoclonus, focal status epilepticus & global regression. WES identified homozygous splice-site variant (p.Ala219Thr) in CARS2.
A 10-year-old boy with motor delay developed action tremor of right hand at age 6, progressing to generalized tremor (rest>action) and rigidity with loss of ambulation by 9. UPDRS-III score- 64 with good levodopa response, later complicated by dyskinesias/motor fluctuations. WES revealed compound heterozygous variants (p.Trp13Gly, p.Tyr171Cys) in WARS2.
A 9-year-old girl, with developmental delay, epileptic spasms and Rett-like stereotypies, developed progressive spastic-ataxic gait from age 8. WES identified compound heterozygous variants (p.Pro364Arg, p.Val95Ile) in PARS2.
A 3.5-year-old girl with global developmental delay & refractory epilepsy had recurrent status dystonicus and lingual dyskinesias. MRI showed cerebral atrophy & cystic basal ganglia. WES identified compound heterozygous variants (p.Thr157Ile, p.Thr496Ile) in TARS2.
A 12-year-old girl presented with profound developmental delay, dysmorphism and spastic-dystonic quadriparesis since infancy. MRI showed globus pallidus hyperintensity. WES revealed homozygous variant (c.293C>T) in EARS2.
Predominant movement phenotypes included cortical myoclonus (CARS2), dystonia-parkinsonism (WARS2), progressive ataxia (PARS2), and dystonia (EARS2, TARS2).
Conclusion: Movement disorders are a prominent but underrecognized feature of m-aaRS-related disorders, spanning a broad spectrum of hyperkinetic and hypokinetic phenomenology.
To cite this abstract in AMA style:
SRC. Roychowdhury, HA. Alfaris, SY. Yoganathan, AM. Menetrey, LMV. M. Vogt, RA. Alayed, LLM. Leblanc-Millar, DC. Cordeiro, LA. Aljouda, CG. Gorodetsky. The Landscape of Movement Disorders in Mitochondrial Aminoacyl t-RNA Synthetase Disorders: A Case Series [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/the-landscape-of-movement-disorders-in-mitochondrial-aminoacyl-t-rna-synthetase-disorders-a-case-series/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-landscape-of-movement-disorders-in-mitochondrial-aminoacyl-t-rna-synthetase-disorders-a-case-series/