Metabolic stroke in a patient with bi-allelic OPA1 mutations

  • Ayelet ZeremEmail author
  • Keren Yosovich
  • Yael Cohen Rappaport
  • Stephanie Libzon
  • Lubov Blumkin
  • Liat Ben-Sira
  • Dorit Lev
  • Tally Lerman-Sagie
Original Article


OPA1 related disorders include: classic autosomal dominant optic atrophy syndrome (ADOA), ADOA plus syndrome and a bi-allelic OPA1 complex neurological disorder. We describe metabolic stroke in a patient with bi-allelic OPA1 mutations. A twelve-year old girl presented with a complex neurological disorder that includes: early onset optic atrophy at one year of age, progressive gait ataxia, dysarthria, tremor and learning impairment. A metabolic stroke occurred at the age of 12 years. The patient was found to harbor a de novo heterozygous frame shift mutation c.1963_1964dupAT; p.Lys656fs (NM_015560.2) and a missense mutation c.1146A > G; Ile382Met (NM_015560.2) inherited from her mother. The mother, aunt, and grandmother are heterozygous for the Ile382Met mutation and are asymptomatic. The co-occurrence of bi-allelic mutations can explain the severity and the early onset of her disease. This case adds to a growing number of patients recently discovered with bi-allelic OPA1 mutations presenting with a complex and early onset neurological disorder resembling Behr syndrome. To the best of our knowledge metabolic stroke has not been described before as an OPA1 related manifestation. It is important to be aware of this clinical feature for a prompt diagnosis and consideration of available treatment.


Mitochondrial disease Neurodegenerative disorder Optic atrophy Behr syndrome Metabolic stroke Next generation sequencing 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest interests.

Informed consent

Informed consent was obtained from the parents for publication in this study.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Metabolic Neurogenetic Service, Pediatric Neurology UnitWolfson Medical CenterHolonIsrael
  2. 2.Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael
  3. 3.Metabolic Neurogenetic Service, Genetics InstituteWolfson Medical CenterHolonIsrael
  4. 4.Division of Pediatric Radiology, Department of Radiology, Dana Children’s HospitalTel-Aviv Medical CenterTel AvivIsrael

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