Protean phenotypic features of the A3243G mitochondrial DNA mutation

Arch Neurol. 2009 Jan;66(1):85-91. doi: 10.1001/archneurol.2008.526.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Mutational Analysis
  • DNA, Mitochondrial / chemistry*
  • Early Diagnosis
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Genotype
  • Heterozygote
  • Humans
  • Inheritance Patterns
  • MELAS Syndrome / diagnosis*
  • MELAS Syndrome / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Surveys and Questionnaires
  • Young Adult

Substances

  • DNA, Mitochondrial