Protean phenotypic features of the A3243G mitochondrial DNA mutation.

OBJECTIVE: To describe the spectrum of clinical symptoms, signs, and laboratory features associated with A3243G, a mitochondrial DNA point mutation that affects multiple organs with varying severity, making the diagnosis and treatment of these patients complex.

DESIGN: Cohort study.

SETTING: Columbia University Medical Center.

PARTICIPANTS: A cohort of 123 matrilineal relatives from 45 families, including 45 fully symptomatic patients with mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (syndrome), 78 carrier relatives, and 30 controls.

MAIN OUTCOME MEASURES: Data gathered from standardized medical history questionnaires, neurological and ophthalmological examination forms, and laboratory tests. We compared data between 3 groups.

RESULTS: Mutation carriers' clinical and laboratory results frequently had many abnormalities. In addition to neurological symptoms, they often had cardiac, endocrine, gastrointestinal, and psychiatric symptoms.

CONCLUSIONS: The A3243G mutation carriers have multiple medical problems, suggesting that the A3243G mutation should be considered as an etiological factor in patients with multisystem clinical presentations or a family history compatible with matrilineal inheritance. Because some medical problems affecting A3243G mutation carriers are treatable, early detection and proactive management may mitigate the burden of morbidity.