Chorea-ballism as a dominant clinical manifestation in heteroplasmic mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome with A3251G mutation in mitochondrial genome: a case report

Abstract

Background Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes, the most common maternally inherited mitochondrial disease, can present with a wide range of neurological manifestations including both central and peripheral nervous system involvement. The most frequent genetic mutation reported in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome is A3243G in MT-TL1 gene. Stroke-like episodes, dementia, epilepsy, lactic acidemia, myopathy, recurrent headaches, hearing impairment, diabetes, and short stature constitute the known presentations in this syndrome. Among the abnormal involuntary movements in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome, myoclonus is the commonest. Other movement disorders, including chorea, are rarely reported in this disorder. Case presentation A 14-year-old South Asian boy from rural Bengal (India), born of a second degree consanguineous marriage, with normal birth and development history, presented with abnormal brief jerky movements involving his trunk and limbs, with recurrent falls for 10 months. We present here a case of heteroplasmic mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome with A3251G mutation, in which the clinical picture was dominated by a host of involuntary abnormal movements including chorea-ballism, myoclonus, and oromandibular dystonia in a backdrop of cognitive decline, seizure, and stroke-like episode. A final diagnosis was established by muscle biopsy and genetic study. Haloperidol was administered to control the involuntary movements along with introduction of co-enzyme Q, besides symptomatic management for his focal seizures. Six months into follow-up his seizures and abnormal movements were controlled significantly with slight improvement of cognitive abilities. Conclusion The dominance of hyperkinetic movements in the clinical scenario and the finding of a point mutation A3251G in MT-TL1 gene make this a rare presentation.

Optic Atrophy and Generalized Chorea in a Patient Harboring an OPA10/RTN4IP1 Pathogenic Variant

“…4 Noteworthy, mitochondrial disorders including MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), AARS2-related disorders, and forms of striatal necrosis can be associated with chorea and dementia. 9,13 Basal ganglia are extremely sensitive to complex I defect and oxidative stress. Pathogenic mechanisms can be the infarction in anoxic tissue with primary or secondary microangiopathy, or production of mitochondrial toxins producing striatal excitotoxic lesions, by a mechanism involving energy depletion in vivo.…”

Spectrum of movement disorders in mitochondrial diseases

“…Marie et al [42] , 1999 Sudarsky et al [43] , 1999 Nakagaki et al [47] , 2005, Kang et al [48] , 2005 Lahiri et al [49] , 2019 MT-TK m.8344G > A Spasmodic dysphonia MERRF Peng et al [44] , 2003 MT-ATP6 m.9176T > C Generalized dystonia/chorea LS Martikainen et al [8] , 2016 MT-ND1 m.3460G > A m.3796G > A Dystonia Adult onset dystonia LHON Spasticity, and core-type myopathy.…”

“…The patient presented at age 24 with involuntary movements that initially involved both hands and further became generalized; by the age of 37, she also developed severe dementia [46] . Few MELAS cases are described with acute-onset chorea often triggered by hyperglycemia [47][48][49] .…”

Effective treatment of choreaballism due to an MT‐CYB variant with haloperidol, tetrabenazine, and antioxidants

“…10 Haloperidol and mitochondrial cocktails have been reported beneficial in some cases with choreaballism. 5,6 Here we present a single patient with mitochondrial choreaballism who profited with regard to choreaballism significantly from symptomatic therapy. The patient underwent routine, clinical investigations, including routine blood tests, cerebrospinal fluid (CSF) investigations, electroencephalography (EEG), cerebral computed tomography (CCT), cerebral magnetic resonance imaging (MRI), needle electromyography (EMG), nerve conduction studies (NCSs), electrocardiography (ECG), and genetic work-up.…”