Chiara Alfonsi (Italy)
Università di Roma La Sapienza Human Neuroscience - Unit of Child Neurology and PsychiatryAuthor Of 1 Presentation
IN-DEPTH PHENOTYPING OF MOVEMENT DISORDERS IN WARS2 ENCEPHALOPATHY
- Federica Rachele Danti (Italy)
Abstract
Background and Aims:
Mitochondrial aminoacyl-tRNA synthetases are essential components of the mitochondrial translation machinery recently associated with a wide spectrum of human diseases. Biallelic mutations in WARS2 gene, which encodes mitochondrial tryptophanyl‐tRNA synthetase, result in early onset neurological disorders, including lethal neonatal encephalomyopathy and milder presentations with pyramidal and extra-pyramidal signs. We aim to assess the neurological phenotype of children with WARS2 related disorders with a focus on movement disorders.
Methods:
We collected clinical, biochemical, genetic, and neuroimaging data of 5 genetically confirmed patients with WARS2 encephalopathy (1 already published and 4 newly reported). Movement disorder phenomenology was characterized in-depth through serial video recordings and medical records review.
Results:
Disease presented within the first 2 years of life with a peculiar action, postural and rest low frequency tremor, which was variably accompanied by deterioration of postural control with axial hypotonia, parkinsonism-dystonia, cerebellar, and pyramidal signs. Three out of five patients, all with severe parkinsonism, carried the recurrent c.37T>G (p.Trp13Gly) variant. Dysautonomic features, dysphagia, gastroparesis, psychiatric issues, epilepsy, and spasticity emerged during the disease course. CSF reduction of homovanillic acid, suggesting brain dopamine depletion, was reported in all patients. An initial good response to levodopa vanished within 2-3 years with residual on-off phenomena in the oldest subjects.
Conclusions:
This cohort confirms WARS2 encephalopathy as an important cause of infantile degenerative parkinsonism with secondary dopamine deficiency. Differently from primary monogenic amines disorders, response to levodopa deteriorates over time mimicking the clinical course observed in Parkinson Disease.