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

Petra Kaufmann, 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

Research output: Contribution to journalArticle

67 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1965-1971
Number of pages7
JournalNeurology
Volume77
Issue number22
DOIs
StatePublished - Nov 29 2011

Fingerprint

MELAS Syndrome
Mitochondrial DNA
Genotype
Natural History
Lactic Acid
Clinical Trials
Mortality
Lateral Ventricles
Neurologic Examination
Point Mutation
Physical Examination
Cohort Studies
Magnetic Resonance Spectroscopy
Prospective Studies
Mutation
Survival
Carrier

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Kaufmann, P., Engelstad, K., Wei, Y., Kulikova, R., Oskoui, M., Sproule, D. M., ... De Vivo, D. C. (2011). Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. Neurology, 77(22), 1965-1971. https://doi.org/10.1212/WNL.0b013e31823a0c7f

Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. / Kaufmann, Petra; Engelstad, K.; Wei, Y.; Kulikova, R.; Oskoui, M.; Sproule, D. M.; Battista, V.; Koenigsberger, D. Y.; Pascual, J. M.; Shanske, S.; Sano, M.; Mao, X.; Hirano, M.; Shungu, D. C.; DiMauro, S.; De Vivo, D. C.

In: Neurology, Vol. 77, No. 22, 29.11.2011, p. 1965-1971.

Research output: Contribution to journalArticle

Kaufmann, P, Engelstad, K, Wei, Y, Kulikova, R, Oskoui, M, Sproule, DM, Battista, V, Koenigsberger, DY, Pascual, JM, Shanske, S, Sano, M, Mao, X, Hirano, M, Shungu, DC, DiMauro, S & De Vivo, DC 2011, 'Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype', Neurology, vol. 77, no. 22, pp. 1965-1971. https://doi.org/10.1212/WNL.0b013e31823a0c7f
Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Sproule DM et al. Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. Neurology. 2011 Nov 29;77(22):1965-1971. https://doi.org/10.1212/WNL.0b013e31823a0c7f
Kaufmann, Petra ; Engelstad, K. ; Wei, Y. ; Kulikova, R. ; Oskoui, M. ; Sproule, D. M. ; Battista, V. ; Koenigsberger, D. Y. ; Pascual, J. M. ; Shanske, S. ; Sano, M. ; Mao, X. ; Hirano, M. ; Shungu, D. C. ; DiMauro, S. ; De Vivo, D. C. / Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. In: Neurology. 2011 ; Vol. 77, No. 22. pp. 1965-1971.
@article{e5d5d5ffced049faaddd7ed245c976ee,
title = "Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype",
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.",
author = "Petra Kaufmann and K. Engelstad and Y. Wei and R. Kulikova and M. Oskoui and Sproule, {D. M.} and V. Battista and Koenigsberger, {D. Y.} and Pascual, {J. M.} and S. Shanske and M. Sano and X. Mao and M. Hirano and Shungu, {D. C.} and S. DiMauro and {De Vivo}, {D. C.}",
year = "2011",
month = "11",
day = "29",
doi = "10.1212/WNL.0b013e31823a0c7f",
language = "English (US)",
volume = "77",
pages = "1965--1971",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "22",

}

TY - JOUR

T1 - Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype

AU - Kaufmann, Petra

AU - Engelstad, K.

AU - Wei, Y.

AU - Kulikova, R.

AU - Oskoui, M.

AU - Sproule, D. M.

AU - Battista, V.

AU - Koenigsberger, D. Y.

AU - Pascual, J. M.

AU - Shanske, S.

AU - Sano, M.

AU - Mao, X.

AU - Hirano, M.

AU - Shungu, D. C.

AU - DiMauro, S.

AU - De Vivo, D. C.

PY - 2011/11/29

Y1 - 2011/11/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=82955225292&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=82955225292&partnerID=8YFLogxK

U2 - 10.1212/WNL.0b013e31823a0c7f

DO - 10.1212/WNL.0b013e31823a0c7f

M3 - Article

C2 - 22094475

AN - SCOPUS:82955225292

VL - 77

SP - 1965

EP - 1971

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 22

ER -