Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Nov 29;77(22):1965-71.
doi: 10.1212/WNL.0b013e31823a0c7f. Epub 2011 Nov 16.

Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype

P Kaufmann  1 , K Engelstad, Y Wei, R Kulikova, M Oskoui, D M Sproule, V Battista, D Y Koenigsberger, J M Pascual, S Shanske, M Sano, X Mao, M Hirano, D C Shungu, S Dimauro, D C De Vivo
Affiliations

Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype

P Kaufmann et al. Neurology. .

Abstract

Objective: To describe the natural history of clinical and laboratory features associated with the m.3243A>G mitochondrial DNA point mutation. Natural history data are needed to obtain prognostic information and for clinical trial planning.

Methods: We included 85 matrilineal relatives from 35 families with at least 2 visits in this prospective cohort study. Thirty-one were fully symptomatic with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and 54 were carrier relatives. Evaluations included standardized questionnaires (medical history and daily living functioning), physical examination, neuropsychological testing, and a battery of imaging and laboratory tests. We evaluated changes in clinical and laboratory features over time and survival. Outcomes are reported over a follow-up period of up to 10.6 years (mean 3.8 ± 2.2 years for patients and 5.5 ± 3.0 for carrier relatives).

Results: Neurologic examination, neuropsychological testing, and daily living scores significantly declined in all patients with MELAS, whereas no significant deterioration occurred in carrier relatives. Cerebral MRI scores declined significantly in patients with MELAS. Magnetic resonance spectroscopy estimates of lactate in the lateral ventricles increased over time, and high lactate was associated with increased mortality. Symptom onset in childhood often was associated with worse outcome. Patients with MELAS had a greater death rate than carrier relatives.

Conclusions: Patients with MELAS carrying the m.3243A>G mutation show a measurable decline in clinical and imaging outcomes. It is hoped that these data will be helpful in anticipating the disease course and in planning clinical trials for MELAS.

PubMed Disclaimer

Figures

Figure
Figure. Kaplan-Meier survival plot
The solid black line represents the 55 fully symptomatic participants with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. The dotted red lines represent the 95% confidence intervals. Survival is plotted in years from disease onset, defined by first seizure or stroke.
See this image and copyright information in PMC

References

    1. Ciafaloni E, Ricci E, Shanske S, et al. MELAS: clinical features, biochemistry, and molecular genetics. Ann Neurol 1992; 31: 391– 398 . - PubMed
    1. Hirano M, Pavlakis SG. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS): current concepts. J Child Neurol 1994; 9: 4– 13 . - PubMed
    1. Goto Y, Nonaka I, Horai S. A new mtDNA mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Biochim Biophys Acta 1991; 1097: 238– 240 . - PubMed
    1. De Vivo DC, DiMauro S. Mitochondrial defects of brain and muscle. Biol Neonate 1990; 58 (Suppl 1): 54– 69 . - PubMed
    1. De Vivo DC. The expanding clinical spectrum of mitochondrial diseases. Brain Dev 1993; 15: 1– 22 . - PubMed

Publication types

Substances