Abstract Details

Title POLG Gene Mutation in a Woman with Progresive External Ophthalmoplegia (PEO), Seizures and Headache

Topic Muscle Disease/Neuromuscular Junction

Presentation(s) P07 - (-)

Poster/Presentation
Number 024

Objective

Background BACKGROUND: Mutations in the gene coding for the catalytic subunit of the mitochondrial DNA polymerase gamma (POLG1) are associated with autosomal and recessive progressive external ophthalmoplegia (PEO) and the spectrum of overlapping mitochondrial syndromes. POLG1 gene mutations are described in children with Alper's disease and responsible for diffuse progressive degeneration of the gray matter.

Design/Methods DESIGN/METHODS: The patient developed migrainous headache before age of 10 years, and seizures at age 29 years, with decline of cognitive capacities. When examined, she had non-fluctuating ptosis with limited eye movements in all directions resulting in persistent diplopia, proximal muscle weakness, cerebellar tremor and dysmetria, and sensory ataxia. She suffers from chronic vertigo, depression and anxiety, and disabling fatigue. She has chronic nausea, vomiting and GI dysmotility. The patient had myocardial infarction at age 49 years. No family member has been afflicted by seizures or other CNS disorders.

Results RESULTS: MRI of brain showed periaqueductal signal abnormality in pons without enhancement and interval growth. Muscle biopsy was consistent with mitochondrial myopathy. The multifocal ERG was normal, while optic coherence tomography demonstrated thinning of the nerve fiber layer. SFEMG showed abnormal jitter, but her visual symptoms did not respond to pyridostigmine, steroids and IVIg. Her seizures were well-controlled with topiramate.

Conclusions CONCLUSIONS: The heterozygous missense mutation c.2590A>G; p.Asn864Asp in the POLG gene is associated with the patient's PEO and CNS symptoms. Epilepsy associated with POLG mutations may preferentially respond to sodium channel blockers. Patients with POLG1 gene mutations are at high risk of death from status epilepticus and from liver failure, especially if exposed to sodium valproate. Supportive therapies such as coenzyme Q10 and modafinil for fatigue may be useful.

Authors/Disclosures
Goran Rakocevic, MD, FAAN (Thomas Jefferson University) PRESENTER	Dr. Rakocevic has nothing to disclose.
Aamir Hussain, MD (UHMP Neurology Geauga Med Ctr)	No disclosure on file
Kader Abdelerahman, MD (Lovelace Neurosciences)	No disclosure on file
A J. Stoessl, MD, FAAN (UBC)	No disclosure on file

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