Disorders of mitochondrial DNA (mtDNA) may commonly present to primary care
physicians but go undiagnosed. A 36-year-old man with a 15-year history of
psychosis, seizures, and sensorineural hearing loss and a family history o
f diabetes mellitus and heart disease presented to our hospital without a u
nifying diagnosis. Physiologic, biochemical, and genetic testing revealed d
eficient aerobic metabolism, a defect in mitochondrial electron transport,
and the presence of an A-to-G point mutation at position 3243 of the mitoch
ondrial leucine-transfer RNA gene, establishing the diagnosis of mitochondr
ial encephalopathy, lactic acidosis, and strokelike syndrome (MELAS). Diagn
osing mtDNA disorders requires a careful integration of clinical signs and
symptoms with pedigree analysis and multidisciplinary testing. Diagnosis is
important to provide genetic counseling, avoid unnecessary evaluation, and
facilitate therapy for symptomatic relief.