These sound like fairly small central scotomas, these would be more typical for nuclear optic neuropathy rather than mitochondrial, or toxic / nutritional. Did you do a work-up for toxic and nutritional causes?
The report states no molecular diagnosis because none of the mitochrondrial or dominant genes are of known pathogenicity.
mt-ATP6 is usually associated with much more severe phenotypes, most commonly NARP (neuropathy, ataxia, and retinitis pigmentosa) as well as developmental delay and myopathy phenotypes. You'd want to examine family members (mom, maternal grandmother, maternal aunts / uncles, siblings, and children) to see if they manifest any findings.
POLG is a mitochondrial DNA maintenance gene, so if this was manifesting in a mitochondrial syndrome, you would expect to see large mitochondrial deletions, you may need a muscle biopsy to see this. POLG is often more common to see CPEO rather than isolated optic neuropathy.
Best,
Drew
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Andrew Carey
Associate Professor
Wilmer Eye Institute, Johns Hopkins Medicine
Baltimore MD
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Original Message:
Sent: 05-06-2025 08:38
From: Lulu Bursztyn
Subject: Bilateral optic atrophy
While I don't have any experience with the MT-ATP6 gene, I certainly have had a number of patients with POLG and optic atrophy. As this can be autosomal dominant, I'm not sure why the report says it "does not establish a molecular diagnosis". In any case, I don't think there's much you can offer, other than the usual mitochondrial disorder advice to avoid tobacco and alcohol, and live a healthy lifestyle.
Lulu
Lulu Bursztyn
Comprehensive and neuro-ophthalmology
Western University, London, Ontario
lulu.bursztyn@sjhc.london.on.ca
519-646-6214
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Original Message:
Sent: 5/5/2025 10:04:00 PM
From: Wen Y. Wu-Chen
Subject: Bilateral optic atrophy
Hello everyone!
I appreciate any thoughts regarding this case.
31 year old female with bilateral optic atrophy. She started noticing some blurry vision around January 2025 difficulty reading small prints, seek help a few months later. Exam: 20/70 0D and 20/60 OS with correction, pale optic nerves bilaterally. Visual fields OU with a para central scotoma predominantly temporal. GCL/IPL: 32OD and 64 OS; RNFL103 0D 96OS. Normal MRI of the brain, orbits and spinal cord; all autoimmune labs were negative, including NMO and MOG.
no family history of any optic neuropathies. Her genetic test came back positive for mitochondrial DNA mutation. See attachment.
Has anyone had experience with this variant? I believe she won't qualify for the genetic therapy. Besides genetic counseling (now she is 6weeks pregnant) and idebenone treatment, any other suggestions?
thanks,
Helena
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Wen Y. Helena Wu-Chen, MD, FAAN
LGHP Neurology Clerkship Site Director
LGHP Neurology | Neuro-ophthalmology
Adjunct Assistant Professor of Neurology, Lewis Katz School of Medicine, Temple University
Neuroscience Institute
2150 Harrisburg Pike, Suite 200A
Office: 717-396-9167 Fax: 717-396-9064
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