The Many Guises of Mitochondrial Disease

Mitochondrial diseases are a heterogeneous group of disorders caused by dysfunction or depletion of the mitochondria. They result from either spontaneous or inherited mutations in the nuclear or mitochondrial DNA. The clinical presentation of patients with mitochondrial disease is variable. Inherited mitochondrial disease can be classified as syndromic or nonsyndromic. Although syndromic mitochondrial diseases are well-known for their acronyms (ie, MELAS, MERRF), they actually represent only a small portion of the known phenotypes. Most mitochondrial diseases are nonsyndromic, with patients demonstrating a variety of symptoms and signs related to dysfunction of multiple organs such as brain, muscle, endocrine, cardiac, or systemic symptoms. Imaging findings include brain atrophy; stroke in an atypical distribution; white matter lesions; atrophy; and symmetric lesions in the brain stem, basal ganglia, and thalami. Many patients have normal imaging findings. Using a case-based format, we illustrate some of the different clinical and radiologic presentations of mitochondrial disorders and discuss the diagnostic approach used at our institution. The diagnosis of mitochondrial disease is challenging due to the variability of clinical presentations, imaging findings, and genetic abnormalities. These entities should be considered in patients with multisystem involvement or single-system involvement without a clear explanation.