Movement Disorders in Children with a Mitochondrial Disease: A Cross-Sectional Survey from the Nationwide Italian Collaborative Network of Mitochondrial Diseases

Abstract

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.

Keywords: childhood onset; mitochondrial disease; movement disorder; multicenter cross-sectional study.

Figure 1

Symptoms preceding the movement disorder (in subjects in whom the movement disorder is not the first clinical feature; n = 56) (A) and comorbidities (B) in our cohort (n = 102), described both for the entire group and for the different movement disorder type-onset subgroups (values reported as percentages).

Figure 2

Level of dependence in activities of daily living and motor functions in mitochondrial patients with movement disorder. (A) Level of dependence in activities of daily living, assessed both at the onset of movement disorder and at the last follow-up. Data were available for 65 patients only. (B) Motor function assessed both at the onset of movement disorder and at the last follow-up. Data on onset motor skills were available for 64 patients; data on last follow-up skills were available for 58 patients. Values are reported as number of patients.

Figure 3

Use and efficacy of pharmacological treatments in patients with mitochondrial movement disorders. Values are reported as number of patients. Blue bars indicate the number of patients for whom the treatment was described as effective in modulating the movement disorder. Orange bars indicate the number of patients for whom the treatment was described as not effective in modulating the movement disorder.