Hearing impairment is common in various phenotypes of the mitochondrial DNA A3243G mutation

Objective: To determine whether there are common symptoms within different phenotypes of the mitochondrial DNA A3243G mutation. Design: A series of 52 adults with mitochondrial encephalomyopathies and th eir symptomatic relatives were screened for the A3243G mutation using restr iction enzyme analysis. In addition to clinical examination, patients with the mutation underwent audiometry, Results: The A3243G mutation was identified in 16 patients (10 index patien ts and 6 symptomatic relatives). Six of these patients presented with strok elike episodes and met the classical criteria of MEL-AS syndrome (mitochond rial myopathy, encephalopathy, lactic acidosis, and strokelike episodes), a nd one had MELAS/MERRF (myoclonic epilepsy with ragged-red fibers) overlap syndrome. Two patients presented with strokelike episodes but did not meet the classical criteria of MELAS. Predominant features of the 8 other patien ts were myopathy with hearing loss and diabetes mellitus (n = 1), chronic p rogressive external ophthalmoplegia (n = 1), diabetes mellitus with hearing loss (n = 1), painful muscle stiffness with hearing loss (n = 1), cardiomy opathy (n = 1), diabetes mellitus (n = 1), and hearing loss (n = 2). In 11 of 16 patients, hearing impairment was obvious on clinical examination. Fur thermore, all 5 patients with normal hearing on clinical examination showed subclinical hearing loss; in 4, hearing loss was more pronounced than age- related hearing impairment and in 1, hearing loss can be age related as wel l. Conclusions: A variety of phenotypes represent the variable multisystemic i nvolvement of the A3243G mutation. Less than half of the patients presented with MELAS, Hearing impairment, the most common symptom, was clinically or subclinically relevant in 15 (94%) of 16 patients.