the eye in cobalamin c defect - organic acidemia associationoptic nerve in cobal c sometimes normal...
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Eye Disease in
Cobalamin C Deficiency Emily McCourt, MD
Pediatric Ophthalmology Children’s Hospital Colorado
University of Colorado
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No Disclosures
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Objectives How the pediatric ophthalmologist evaluates vision /
retina in young patients
Understand what we know about the structure of the
eye/retina in Cobalamin C deficiency and also the
function
Review of literature
Low vision
Your questions, answered
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Pediatric eye exam
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Nystagmus
What does this mean?
When does it develop?
Will it ever go away?
Strabismus
Pediatric eye exam
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Slit lamp exam
Cataract (lens opacity)
Dilated exam
Retina
Optic Nerve
Pediatric eye exam
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What I see
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More complex testing
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Optic Nerve in Cobal C Sometimes normal
Often pale
Part of the eye but also part of the brain.
Optic nerve atrophy:
Can be seen in Cobalamin disorders (G) and many other
disorders.
Very common and very NON specific – can have a LARGE
range of visual function with optic nerve atrophy.
We can measure this with OCT… more to come on this.
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The Retina in Cobal C Defect This is more interesting to me because:
It’s appearance is very characteristic. Few other
diseases have retinas that look like this
It’s variable – not every patient has this
I’m hopeful that the clues to understanding what is
happening early in the retina will lead to improved
treatments and one day a cure.
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Normal right retina
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Normal left retina
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While some of my patients
have normal retinas, most do
not
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Advanced disease
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Patient 1 Compound heterozygosity for an MMACHC (p.Y205X)
mutation and an intragenic deletion
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4 months old
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8 months old
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24 months old
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4 months old
8 months old
24 months old
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Patient 2 homozygous variant, c.271dupA, p.R91KfsX14.
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6 months old
12 months old
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Patient 3 homozygous for c.271dupA allele (p.Arg91LysfsX14)
Normal exam, now 11 months old
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Patient 4 Two heterozygous pathogenic variants in MMACHC:
c.271dupA (p.R91Kfs*14)
and
c.440G>A (p.G147D).
Normal exam, now 8 months old
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Let’s look closer at the retina
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Patient 1
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4 months old 8 months old
R R
L L
Normal
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Patient 2
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R
L L
R
6 months old 12 months old
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What’s in the literature?
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• 2014
• 12 patients
• Average age of exam 10 years old
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MACULOPATHY: 8/12 patients
Nystagmus: 8/12 patients
Optic nerve atrophy: 6/12 patients
VISION: Visual function was age appropriate in 3/12 patients.
None of these 3 patients had nystagmus, maculopathy OR
optic atrophy
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Review of the current literature – 55 early onset and 38
with late onset disease
Added 7 more of our cases
Overall: 62 patients with early onset CblC
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About half of the patients had enough information
documented to study. Of those:
5% had normal vision
10% were mildly visually impaired (20/30-20/40)
5% moderate visual impairment (20/50-20/80)
21% with moderate to severe impairment (20/100-20/800)
31% severely impaired (worse than 20/800)
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Framework for standardizing exams so we can understand
natural history better.
6 months – baseline testing
12 months – repeat testing
18 months - office
24 months – repeat testing
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By far the most comprehensive study – NIH
25 patients
72% macular degeneration
64% nystagmus
52% strabismus
68% optic nerve atrophy
Ophthalmology 2016;123:571-582
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Ophthalmology 2016;123:571-582
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11 patients
OCT
ALL with early onset disease had maculopathy and
poor vision
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Answers to some questions
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Unanswered questions Why do some patients have disease and others don’t?
Can we do gene therapy? (not yet…..)
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What you CAN do Vision therapy – NO!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
http://www.aapos.org/terms/conditions/108
Vision rehabilitation – YES.
This is maximizing what you have.
Teachers for the visually impaired
Anchor center for the Blind
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What you CAN do Treating refractive error, strabismus.
Seeing an ophthalmologist who is interested in this
disease so we can work as a team
www.aapos.org