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

Ticci, Chiara; Orsucci, Daniele; Ardissone, Anna; Bello, Luca; Bertini, E.; Bonato, Irene; Bruno, Claudio; Carelli, Valerio; Diodato, Daria; Doccini, Stefano; Dosi, Claudia; Filosto, Massimiliano; Morgia, Chiara La; Lamperti, Costanza; Marchet, Silvia; Martinelli, Diego; Minetti, Carlo; Moggio, Maurizio; Mongini, Tiziana; Montano, Vincenzo; Moroni, Isabella; Musumeci, Olimpia; Pancheri, Elia; Pegoraro, Elena; Primiano, Guido; Procopio, Elena; Rubegni, Anna; Scalise, Roberta; Sciacco, Monica; Servidei, Serenella; Siciliano, Gabriele; Simoncini, Costanza; Tolomeo, Deborah; Tonin, Paola; Toscano, Antonio; Tubili, Flavia; Mancuso, Michelangelo; Battini, Roberta; Santorelli, Filippo M.

doi:10.3390/jcm10102063

Cited by 15 publications

(16 citation statements)

References 40 publications

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“…Since the registry does not contain a specific dataset for a detailed characterization of the movement disorders features, an online 50-item Google Form ® -based questionnaire was sent by email to all centers following adult PMDs (supplementary Table 1). The present study does not include patients with NARP, Leigh or other pediatric mitochondrial syndromes, that have movement disorders among the core clinical features [ 6 ], which are described separately [ 7 ].…”

Section: Methodsmentioning

confidence: 99%

Adult-onset mitochondrial movement disorders: a national picture from the Italian Network

Montano

Orsucci²,

Carelli

et al. 2021

J Neurol

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Introduction Both prevalence and clinical features of the various movement disorders in adults with primary mitochondrial diseases are unknown. Methods Based on the database of the “Nation-wide Italian Collaborative Network of Mitochondrial Diseases”, we reviewed the clinical, genetic, neuroimaging and neurophysiological data of adult patients with primary mitochondrial diseases (n = 764) where ataxia, myoclonus or other movement disorders were part of the clinical phenotype. Results Ataxia, myoclonus and movement disorders were present in 105/764 adults (13.7%), with the onset coinciding or preceding the diagnosis of the mitochondrial disease in 49/105 (46.7%). Ataxia and parkinsonism were the most represented, with an overall prevalence at last follow-up of 59.1% and 30.5%, respectively. Hyperkinetic movement disorders were reported in 15.3% at last follow-up, being the less common reported movement disorders. The pathogenic m.8344A > G and POLG variants were always associated with a movement disorder, while LHON variants and mtDNA single deletions were more commonly found in the subjects who did not present a movement disorder. The most common neuroimaging features were cortical and/or cerebellar atrophy, white matter hyperintensities, basal ganglia abnormalities and nigro-striatal degeneration. Almost 70% of patients with parkinsonism responded to dopaminergic therapy, mainly levodopa, and 50% with myoclonus were successfully treated with levetiracetam. Conclusion Movement disorders, mainly ataxia and parkinsonism, are important findings in adult primary mitochondrial diseases. This study underlies the importance of looking for a mitochondrial etiology in the diagnostic flowchart of a movement disorder and may help direct genetic screening in daily practice.

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Section: Methodsmentioning

confidence: 99%

Adult-onset mitochondrial movement disorders: a national picture from the Italian Network

Montano

Orsucci²,

Carelli

et al. 2021

J Neurol

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“…Recent studies on a childhood-onset PMDs cohort reported ataxia being the most common movement disorder at onset (49% of individuals) [ 7 ]. Furthermore, ataxia and parkinsonism were the most represented movement disorders in a large cohort of mitochondrial patients from an Italian registry, with an overall prevalence at last follow-up of 59.1% and 30.5%, respectively [ 8 ].…”

Section: Mitochondrial Ataxiasmentioning

confidence: 99%

“…Within the CNS pathological manifestations of PMDs, movement disorders, either hypo- or hyperkinetic, have been reported. The relative incidence, features and spectrum of these conditions are still largely unknown and are currently being investigated [ 6 ] A recent clinical cross-sectional investigation on an Italian cohort of individuals with childhood-onset PMDs, reported that a movement disorder was present at the onset of 40% of patients, appearing on average five years before it [ 7 ]. In adults, parkinsonism is often described, whereas, in the paediatric population, chorea and dystonia are common manifestations.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Ataxias: Molecular Classification and Clinical Heterogeneity

Lopriore

Ricciarini

Siciliano

et al. 2022

Neurology International

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Ataxia is increasingly being recognized as a cardinal manifestation in primary mitochondrial diseases (PMDs) in both paediatric and adult patients. It can be caused by disruption of cerebellar nuclei or fibres, its connection with the brainstem, or spinal and peripheral lesions leading to proprioceptive loss. Despite mitochondrial ataxias having no specific defining features, they should be included in hereditary ataxias differential diagnosis, given the high prevalence of PMDs. This review focuses on the clinical and neuropathological features and genetic background of PMDs in which ataxia is a prominent manifestation.

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“…In a nationwide Italian survey of 764 patients with MID, a movement disorder was found in 13.7% of patients 8 . In a cross‐sectional survey of 102 children with MID from Italy, a movement disorder was the presenting phenotypic feature in 45 individuals with an average age of 11 years 9 . The most common movement disorder in this cohort was ataxia (actually not classified as such by the International Movement disorder Society) followed by dystonia, tremor, hypokinetic disorders, chorea, and myoclonus 9 .…”

Section: Introductionmentioning

confidence: 99%

“…In a cross‐sectional survey of 102 children with MID from Italy, a movement disorder was the presenting phenotypic feature in 45 individuals with an average age of 11 years 9 . The most common movement disorder in this cohort was ataxia (actually not classified as such by the International Movement disorder Society) followed by dystonia, tremor, hypokinetic disorders, chorea, and myoclonus 9 . The pathophysiological basis of movement disorders in MIDs is an affection of the basal ganglia or the midbrain.…”

Section: Introductionmentioning

confidence: 99%

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

Finsterer¹,

Ghosh

2023

Clinical Case Reports

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Hypokinetic and hyperkinetic movement disorders are a common phenotypic feature of mitochondrial disorders. Choreaballism has been reported particularly in patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome and in maternally inherited diabetes and deafness syndrome.The pathophysiological basis of movement disorders in mitochondrial disorders is the involvement of the basal ganglia or the midbrain. Haloperidol and mitochondrial cocktails have proven beneficial in some of these cases. Here we present another patient with mitochondrial choreaballism who benefited significantly from symptomatic therapy. The patient is a 14-year-old male with a history of hypoacusis, ptosis, and focal tonic-clonic seizures of the upper/lower limbs on either side since childhood. Since this time he has also developed occasional, abnormal involuntary limb movements, choreaballism, facial grimacing, carpopedal spasms, and abnormal lip sensations. He was diagnosed with a non-syndromic mitochondrial disorder after detection of the variant m.15043G > A in MT-CYB.Seizures have been successfully treated with lamotrigine. Hypocalcemia was treated with intravenous calcium. For hypoparathyroidism calcitriol was given.Choreaballism was treated with haloperidol and tetrabenazine. In addition, he received coenzyme Q10, L-carnitine, thiamine, riboflavin, alpha-lipoic acid, biotin, vitamin-C, vitamin-E, and creatine-monohydrate. With this therapy, the choreaballism disappeared completely. This case shows that mitochondrial disorders can manifest with cognitive impairment, seizures, movement disorder, hypoacusis, endocrinopathy, cardiomyopathy, neuropathy, and myopathy, that choreaballism can be a phenotypic feature of multisystem mitochondrial disorders, and that choreaballism favorably responds to haloperidol, tetrabenazine, and possibly to a cocktail of antioxidants, cofactors, and vitamins.

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

Cited by 15 publications

References 40 publications

Adult-onset mitochondrial movement disorders: a national picture from the Italian Network

Adult-onset mitochondrial movement disorders: a national picture from the Italian Network

Mitochondrial Ataxias: Molecular Classification and Clinical Heterogeneity

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

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