title: Retrospective study of a large population of patients affected with mitochondrial disorders: clinical, morphological and molecular genetic evaluation.
abstract: Mitochondrial disorders are human genetic diseases with extremely variable clinical and genetic features. To better define them, we made a genotype-phenotype correlation in a series of 207 affected patients, and we examined most of them with six laboratory examinations (serum CK and basal lactate levels, EMG, cardiac and EEG studies, neuroradiology). We found that, depending on the genetic abnormality, hyperckemia occurs most often with either chronic progressive external ophthalmoplegia (CPEO) and ptosis or with limb weakness. Myopathic EMGs are more common than limb weakness, except in patients with A8344G mutations. Peripheral neuropathy, when present, is always axonal. About 80% of patients with A3243G and A8344G mutations have high basal lactate levels, whereas pure CPEO is never associated with increased lactate levels. Cardiac abnormalities mostly consist of conduction defects. Abnormalities on CT or MRI of the brain are relatively common in A3243G mutations independently of the clinical phenotype. Patients with multiple mtDNA deletions are somehow "protected" against the development of abnormalities with any of the tests. We conclude that, despite the phenotypic heterogeneity of mitochondrial disorders, correlation of clinical features and laboratory findings may give the clinician important clues to the genetic defect, allowing earlier diagnosis and counselling.
authors.affiliation: Centro Dino Ferrari, Istituto di Clinica Neurologica, University of Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Sciacco
authors.forename: A
authors.initials: A
authors.lastname: Prelle
authors.forename: G P
authors.initials: GP
authors.lastname: Comi
authors.forename: L
authors.initials: L
authors.lastname: Napoli
authors.forename: A
authors.initials: A
authors.lastname: Battistel
authors.forename: N
authors.initials: N
authors.lastname: Bresolin
authors.forename: L
authors.initials: L
authors.lastname: Tancredi
authors.forename: C
authors.initials: C
authors.lastname: Lamperti
authors.forename: A
authors.initials: A
authors.lastname: Bordoni
authors.forename: G
authors.initials: G
authors.lastname: Fagiolari
authors.forename: P
authors.initials: P
authors.lastname: Ciscato
authors.forename: L
authors.initials: L
authors.lastname: Chiveri
authors.forename: M P
authors.initials: MP
authors.lastname: Perini
authors.forename: F
authors.initials: F
authors.lastname: Fortunato
authors.forename: L
authors.initials: L
authors.lastname: Adobbati
authors.forename: S
authors.initials: S
authors.lastname: Messina
authors.forename: A
authors.initials: A
authors.lastname: Toscano
authors.forename: F
authors.initials: F
authors.lastname: Martinelli-Boneschi
authors.forename: A
authors.initials: A
authors.lastname: Papadimitriou
authors.forename: G
authors.initials: G
authors.lastname: Scarlato
authors.forename: M
authors.initials: M
authors.lastname: Moggio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003402:Creatine Kinase / Q000097:blood; D004272:DNA, Mitochondrial / Q000235:genetics*; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D017353:Gene Deletion; D006321:Heart / Q000503:physiopathology; D006801:Humans; D007223:Infant; D019344:Lactic Acid / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed
chemical_list: D004272:DNA, Mitochondrial; D019344:Lactic Acid; D003402:Creatine Kinase