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MELAS: A Multigenerational Impact of the MTTL1 A3243G MELAS Mutation

Published online by Cambridge University Press:  23 September 2014

M. Prasad
Affiliation:
1Western University and London Health Sciences Centre, London
B. Narayan
Affiliation:
1Western University and London Health Sciences Centre, London
A.N. Prasad
Affiliation:
Departments of Paediatrics, London
C.A. Rupar
Affiliation:
Departments of Paediatrics, London Pathology and Laboratory Medicine, London Biochemistry, London Children's Health Research Institute, London
S. Levin
Affiliation:
Departments of Paediatrics, London
J. Kronick
Affiliation:
Department of Paediatrics, Hospital for Sick Children, Toronto, Ontario, Canada
D. Ramsay
Affiliation:
Pathology and Laboratory Medicine, London
K.Y. Tay
Affiliation:
Medical Imaging, London
C. Prasad
Affiliation:
Departments of Paediatrics, London Children's Health Research Institute, London
Corresponding
E-mail address:
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Abstract

Background:

the maternally inherited MTTL1 A3243G mutation in the mitochondrial genome causes MelaS (Mitochondrial encephalopathy lactic acidosis with Stroke-like episodes), a condition that is multisystemic but affects primarily the nervous system. Significant intra-familial variation in phenotype and severity of disease is well recognized.

Methods:

retrospective and ongoing study of an extended family carrying the MTTL1 A3243G mutation with multiple symptomatic individuals. tissue heteroplasmy is reviewed based on the clinical presentations, imaging studies, laboratory findings in affected individuals and pathological material obtained at autopsy in two of the family members.

Results:

there were seven affected individuals out of thirteen members in this three generation family who each carried the MTTL1 A3243G mutation. the clinical presentations were varied with symptoms ranging from hearing loss, migraines, dementia, seizures, diabetes, visual manifestations, and stroke like episodes. three of the family members are deceased from MelaS or to complications related to MelaS.

Conclusions:

the results of the clinical, pathological and radiological findings in this family provide strong support to the current concepts of maternal inheritance, tissue heteroplasmy and molecular pathogenesis in MelaS. neurologists (both adult and paediatric) are the most likely to encounter patients with MelaS in their practice. genetic counselling is complex in view of maternal inheritance and heteroplasmy. newer therapeutic options such as arginine are being used for acute and preventative management of stroke like episodes.

Type
Original Article
Copyright
Copyright © The Canadian Journal of Neurological 2014

References

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