Retrospective study of patients affected of a large population with mitochondrial disorders: clinical, morphological and molecular genetic evaluation

Mitochondrial disorders are human genetic diseases with extremely variable clinical and genetic features. To better define them, we made a genotype-ph enotype correlation in a series of 207 affected patients, and we examined m ost of them with six laboratory examinations (serum CK and basal lactate le vels, EMG, cardiac and EEG studies, neuroradiology). We found that, dependi ng on the genetic abnormality, hyperckemia occurs most often with either ch ronic progressive external ophthalmoplegia (CPEO) and ptosis or with limb w eakness. Myopathic EMGs are more common than limb weakness, except in patie nts with A8344G mutations. Peripheral neuropathy, when present, is always a xonal. About 80 % of patients with A3243G and A8344G mutations have high ba sal lactate levels, whereas pure CPEO is never associated with increased la ctate levels. Cardiac abnormalities mostly consist of conduction defectsAbn ormalities on CT or MRI of the brain are relatively common in A3243G mutati ons independently of the clinical phenotype. Patients with multiple mtDNA d eletions are somehow "protected" against the development of abnormalities w ith any of the tests. We conclude that, despite the phenotypic heterogeneit y of mitochondrial disorders, correlation of clinical features and laborato ry findings may give the clinician important clues to the genetic defect, a llowing earlier diagnosis and counselling.