Movement Disorders in Children with a Mitochondrial Disease: A Cross-Sectional Survey from the Nationwide Italian Collaborative Network of Mitochondrial Diseases.
Chiara TicciDaniele OrsucciAnna ArdissoneLuca BelloEnrico BertiniIrene BonatoClaudio BrunoValerio CarelliDaria DiodatoStefano DocciniMaria Alice DonatiClaudia DosiMassimiliano MirabellaChiara FiorilloChiara La MorgiaCostanza LampertiSilvia MarchetDiego MartinelliCarlo MinettiMaurizio MoggioTiziana Enrica MonginiVincenzo MontanoIsabella MoroniOlimpia MusumeciElia PancheriElena PegoraroGuido PrimianoElena ProcopioAnna RubegniRoberta ScaliseMonica SciaccoSerenella ServideiGabriele SicilianoCostanza SimonciniDeborah TolomeoPaola ToninAntonio ToscanoFlavia TubiliMichelangelo MancusoRoberta BattiniFilippo Maria SantorelliPublished in: Journal of clinical medicine (2021)
Movement disorders are increasingly being recognized as a manifestation of childhood-onset mitochondrial diseases (MDs). However, the spectrum and characteristics of these conditions have not been studied in detail in the context of a well-defined cohort of patients. We retrospectively explored a cohort of individuals with childhood-onset MDs querying the Nationwide Italian Collaborative Network of Mitochondrial Diseases database. Using a customized online questionnaire, we attempted to collect data from the subgroup of patients with movement disorders. Complete information was available for 102 patients. Movement disorder was the presenting feature of MD in 45 individuals, with a mean age at onset of 11 years. Ataxia was the most common movement disorder at onset, followed by dystonia, tremor, hypokinetic disorders, chorea, and myoclonus. During the disease course, most patients (67.7%) encountered a worsening of their movement disorder. Basal ganglia involvement, cerebral white matter changes, and cerebellar atrophy were the most commonly associated neuroradiological patterns. Forty-one patients harbored point mutations in the mitochondrial DNA, 10 carried mitochondrial DNA rearrangements, and 41 cases presented mutations in nuclear-DNA-encoded genes, the latter being associated with an earlier onset and a higher impairment in activities of daily living. Among our patients, 32 individuals received pharmacological treatment; clonazepam and oral baclofen were the most commonly used drugs, whereas levodopa and intrathecal baclofen administration were the most effective. A better delineation of the movement disorders phenotypes starting in childhood may improve our diagnostic workup in MDs, fine tuning management, and treatment of affected patients.
Keyphrases
- end stage renal disease
- ejection fraction
- newly diagnosed
- mitochondrial dna
- chronic kidney disease
- peritoneal dialysis
- white matter
- copy number
- randomized controlled trial
- oxidative stress
- transcription factor
- deep learning
- deep brain stimulation
- parkinson disease
- genome wide
- smoking cessation
- combination therapy
- big data
- dna methylation
- adverse drug
- single molecule
- replacement therapy
- nucleic acid