Disorders of movement in Leigh syndrome
Child; Female; Humans; Male; Magnetic Resonance Imaging; Preschool; Q3 Literature Search; retrospective studies; Basal Ganglia Diseases/complications/enzymology/physiopathology; Basal Ganglia/enzymology/physiopathology; Brain/enzymology/physiopathology/radiography; Dystonia/complications/diagnosis/physiopathology; Electron Transport Complex IV/metabolism; Enzyme Repression; Leigh Disease/complications/diagnosis/physiopathology; Mental Disorders/etiology; Mitochondrial Encephalomyopathies/complications/enzymology; Movement Disorders/complications/diagnosis/physiopathology
Leigh syndrome (LS) is the clinical prototype of a genetically-determined mitochondrial encephalopathy. Twenty-two of 34 patients with LS had evidence of a movement disorder (MD). Dystonia, the most common MD, was present in 19 cases, rigidity in 4, tremor in 2, chorea in 2, hypokinesia in 2, myoclonus in 1, and tics in 1. Dystonia was most commonly multifocal at onset and showed progression in six patients. In half of the cases an enzymatic defect was detected, most commonly cytochrome C oxidase. The neuroradiologic findings showed prominent basal ganglia lesions in 20/21 patients. Putamen, caudate, substantia nigra and globus pallidus were involved in this order of frequency. This experience was reflected in a literature review encompassing 284 cases of LS. However, only 26.4% had MD. Eleven patients, including one of our cases, presented as the primary torsion dystonia phenotype. There are clinical and pathological similarities between LS and other metabolic diseases affecting the central nervous system. The enhanced vulnerability of the nervous system to metabolic stress and the resemblance in the distribution of the pathology of these diverse conditions suggests a common pathogenetic mechanism. An excitotoxin-mediated mechanism is favored, one which might account for the frequent involvement of the basal ganglia in LS.
1993
Macaya A; Munell F; Burke RE; De Vivo DC
Neuropediatrics
1993
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1055/s-2008-1071515" target="_blank" rel="noreferrer">10.1055/s-2008-1071515</a>
Unusual clinical presentations in four cases of Leigh disease, cytochrome C oxidase deficiency, and SURF1 gene mutations
Female; Humans; infant; Male; Phenotype; infant; Q3 Literature Search; Newborn; DNA Mutational Analysis; Muscle; Skeletal/pathology; Proteins/genetics; Frameshift Mutation; Cytochrome-c Oxidase Deficiency/complications/genetics/pathology; Kidney Diseases/etiology; Leigh Disease/complications/genetics/pathology; Membrane Proteins; Mitochondrial Proteins
Mutations in the SURF1 gene are the most frequent causes of Leigh disease with cytochrome c oxidase deficiency. We describe four children with novel SURF1 mutations and unusual features: three had prominent renal symptoms and one had ragged red fibers in the muscle biopsy. We identified five pathogenic mutations in SURF1: two mutations were novel, an in-frame nonsense mutation (834G-->A) and an out-of-frame duplication (820-824dupTACAT). Although renal manifestations have not been described in association with SURF1 mutations, they can be part of the clinical presentation. Likewise, mitochondrial proliferation in muscle (with ragged red fibers) is most unusual in Leigh disease but might be part of an emerging phenotype.
2005
Tay SK; Sacconi S; Akman HO; Morales JF; Morales A; De Vivo DC; Shanske S; Bonilla E; DiMauro S
Journal Of Child Neurology
2005
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1177/08830738050200080701" target="_blank" rel="noreferrer">10.1177/08830738050200080701</a>